Case Summary David McGrath, 50 year old male presents with burning chest and stomach pain.

Pain is nocturnal, does not spread, has been present for 6 months, fluctuates in severity throughout the day, and usually worsens after a meal. He is an obese smoker and occasional drinker with a previous history of an appendectomy and a broken arm. Upon physical examination patient is found to be hypertensive with a BP of 130/90, a pulse rate of 80 beats/min, normal temperature, a fluctuant weight over the past 6 months, with some broken veins on his nose. A diagnosis of GERD is suggested with a possibility of a gastric ulcer and therefore an endoscopy is performed with biopsies taken at the lower esophageal mucosa and gastric antral mucosa. He is also prescribed ranitidine and is recommended to watch his diet. Endoscopy report showed a small polyp at the gastro-esophageal junction, moderate/severe esophagitis, and columnar lined esophageal epithelium. Biopsy histology revealed ulceration, gastric mucosa metaplasia, and features of reflux esophagitis in the esophagus epithelium with presence of H. Pylori bacteria in the gastric antrum, which is associated with chronic gastritis.

1. Explain GORD and peptic ulcers (gastric and duodenal) and how they are diagnosed/managed. Gastro-Esophageal Reflux Disorder - When the amount of gastric juice that refluxes out of the stomach into the esophagus (abnormally) exceeds the normal limit Commonly presents as heartburn and regurgitation upon lying down. Also presents with nocturnal cough, dyspnea, adult onset asthma and decreased LES tone. VII. GASTROESOPHAGEAL REFLUX DISEASE (GERD) A. Reflux of acid from the stomach due to reduced LES tone - B. Risk factors include alcohol, tobacco, obesity, fat rich diet, caffeine, and hiatal hernia. Also over eating, eating before bed. Pathology note: In a sliding hiatal hernia, the esophagogastric junction herniates upward through the esophageal hiatus in the diaphragm. This removes the contribution to LES tone provided by the diaphragm and predisposes to reflux. In a rolling (paraesophageal) hiatal hernia, the esophagogastric junction remains fixed in place, and LES tone remains largely preserved. These patients therefore are less likely to suffer from reflux, although there is some concern for incarceration.

Medication o Nicotine, NSAIDs, Alcohol Pregnancy o Increased gastric pressure o Increased estrogen and progesterone Collagen Vascular Disease o Scleroderma o Mixed connective tissue disease o Systemic lupus erythmatosus

C. Clinical features 1. Heartburn (mimic scardiac chest pain) 2. Asthma (adult-onset) and cough 3. Damage to enamel of teeth 4. Ulceration with stricture and Barrett esophagus are late complications. Ingastroesophageal reflux disease (GERD), the mucosal epithelium of the esophagus takes on the appearance of the gastric mucosal epitheliumit differentiates from a stratified squamous epithelium into a columnar epithelium. This process, whereby one cell type transforms into another, is termed metaplasia. Columnar metaplasia in the lower esophagus is called Barrett esophagus, which can be detected by endoscopy and substantially increases the risk for development of esophageal adenocarcinoma and stricture from scarring. Patients who develop Barrett esophagus require periodic endoscopic surveillance

VIII.BARRETT ESOPHAGUS

A. Metaplasia of the lower esophageal mucosa from stratified squamous epithelium to non ciliated columnar epithelium with goblet cells. Seen in 10% of patients with GERD. - It is a response of lower esophageal stem cells to acidic stress. B. May progress to dysplasia and adenocarcinoma

Opening of the lower esophageal sphincter (LES) When not eating, the LES is normally tonically constricted, in part because of the additional sphincteric pressure provided by the diaphragm. This helps prevent reflux of gastric contents into the esophagus. When eating, the LES relaxes in response to swallowing (deglutition) and distension of the esophagus. This relaxation is mediated both by vagal stimulation and by some intrinsic properties of the LES

1. What are peptic (gastric or duodenal) ulcers and what are the causes of each?

Mucous cells If it were not for the protective activity of mucous cells, which secrete mucus and HCO3-, the low gastric pH would continually damage the gastric mucosa and predispose to ulcers. The mucous layer protects the gastric mucosa by preventing back diffusion of H+ ions into the gastric mucosa Beneath this mucous layer, a layer rich in HCO3- neutralizes H+ as it passes through the mucous barrier. In addition, the alkaline HCO3- layer prevents activation of any pepsinogen that escapes through the mucous layer. Clinical note: Mucosal blood flow is highly dependent on the local production of prostaglandins. Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, can impair mucosal blood flow by inhibiting prostaglandin synthesis. This compromises the protective abilities of the mucosa (mucus and HCO3- secretion) and can cause irritation of the mucosa (gastritis) or even ulceration(peptic ulcer disease). In fact, it is not uncommon for elderly people to be admitted to the hospital with active upper intestinal bleeding, with concomitant anemia, owing to the recent use of NSAIDs.

VI, P E P T I C ULCER D I S E A S E A. Solitary mucosal ulcer involving proximal duodenum (90%) or distal stomach (10%) B. Duodenal ulcer is almost always due to H pylori (> 95%); rarely, may be due to ZE Syndrome. 1. Presents with epigastric pain that improves with meals 2. Diagnostic endoscopic biopsy shows ulcer with hypertrophy of Brunner glands. 3. May rupture leading to bleeding from the gastroduodenal artery (anterior ulcer) or acute pancreatitis (posterior ulcer)

C. Gastric ulcer is usually due to H pylori (75%); other causes include NSAlDs and bile reflux. 1. Presents with epigastric pain that worsens with meals 2. Ulcer is usually located on the lesser curvature of the antrum. 3. Rupture carries risk of bleeding from left gastric artery.

D. Differential diagnosis of ulcers includes carcinoma. 1, Duodenal ulcers are almost never malignant (duodenal carcinoma is extremely rare). 2. Gastric ulcers can be caused by gastric carcinoma (intestinal subtype). i. Benign peptic ulcers are usually small (< 3 cm), sharply demarcated ("punched-out"), and surrounded by radiating folds of mucosa (Fig. 10.13A). ii. Malignant ulcers are large and irregular with heaped up margins (Fig. 10.13B) iii. Biopsy is required for definitive diagnosis.

VII, GASTRIC CARCINOMA A. Malignant proliferation of surface epithelial cells (adenocarcinoma) B. Subclassilied into intestinal and diffuse types C. Intestinal type (more common) presents as a large, irregular ulcer with heaped up margins; most commonly involves the lesser curvature of the antrum (similar to gastric ulcer) 1. Risk factors include intestinal metaplasia (e.g., due to H pylori and autoimmune gastritis), nitrosamines in smoked foods (Japan), and blood type A. D. Diffuse type is characterized by signet ring cells that diffusely infiltrate the gastric wall (Fig. 10.14B); desmoplasia results in thickening of stomach wall (linitis plasties, Fig, 10.I4A). 1, Not associated with H pylori, intestinal metaplasia, or nitrosamines E. Gastric carcinoma presents late with weight loss, abdominal pain, anemia, and early satiety; rarely presents as acanthosis nigricans or Leser-Trelat sign

F. Spread to lymph nodes can involve the left supraclavicular node (Virchow node). G. Distant metastasis most commonly involves liver; other sites include q. . Periumbilical region (Sister Mary Joseph nodule); seen with intestinal type

Peptic Ulcer Disease Erosion (superficial to the muscularis mucosa) or ulcers (penetrates the muscularis muscosa scarring) - Generally two types: gastric (stomach) and duodenal o Gastric ulcers have the potential for maligancy while duodenal ulcer are rarely malignant - Gastric ulcers o Not all gastric ulcers are peptic ulcers could be ulcerating cancer o Occur in the alkaline-producing mucosa of the stomach, at the antrum and pyloric canal o Chronic ulcers invade the muscular coats and involves the peritoneum so that the stomach adheres to neighboring structures o An ulcer on the posterior wall of the stomach may perforate into the lesser sac or become adherent to the pancreas o A penetrating ulcer of the anterior stomach wall may result in the escape of stomach contents into the greater sac, producing diffuse peritonitis or the anterior stomach wall may adhere to the liver, and the chronic ulcer may penetrate into the liver itself Causes of Peptic Ulcers H. Pylori Infection Drugs o NSAIDs disrupt the mucosal permeability barrier leaving epithelial cells vulnerable to injury o 30% of NSADs users have GI adverse effects o NSAIDs and H. Pylori exert a synergistic effect to the development of ulcers

Lifestyle Factors o Smoking harmful to the GI mucosa so increases vulnerability to H. Pylori o Drinking causes gastric mucosa irritation Physiologic Stress o Burns, CNS trauma, surgery, medical illnesses, and systemic illnesses Hypersecretory States (uncommon) o Zollinger-Ellison Syndrome, G-cell hyperplasia, cystic fibrosis, basophilic leukemia, hyperparathyroidism, short bowel syndrom Genetic Factors

IX.ESOPHAGEAL CARCINOMA A. Subclassified as adenocarcinoma or squamous cell carcinoma B. Adenocarcinoma is a malignant proliferation of glands; most common type of esophageal carcinoma in the West I .Arises from preexisting Barrett esophagus; usually involves the lower one-third of the esophagus

C. Squamous cell carcinoma is a malignant proliferation of squamous cells; most common esophageal cancer worldwide 1.Usually arises in upper or middle third of the esophagus; major risk, factors Include i .Alcohol and tobacco(most common causes) ii. Very hot tea til. Achalasia iv. Esophageal web (e.g.,Plummer-Vinson syndrome ) v. Esophageal injury (e.g., lye ingestion ) D. Esophageal carcinoma presents late (poor prognosis). 1. Symptoms include progressive dysphagia (solids to liquids), weight loss, pain, and hematemesis. 2. Squamous cell carcinoma may additionally present with hoarse voice (recurrent laryngeal nerve involvement) and cough (tracheal involvement) .

E, location of lymph node spread depends on the level of the esophagus that is involved . 1.Upper1/3cervical nodes 2.Middle1/3mediastinal or tracheobronchial nodes 3.Lower1/3celiac and gastric nodes