Internal Medicine Board Review 2010: Gastroenterology

1. Internal Medicine Board Review 2010: Gastroenterology

2. Esophagus • Dysphagia • Mechanical vs. Motility Disorders • Gastroesophageal Reflux Disease • Extra esophageal manifestations • Barrett’s Esophagus • Esophageal Cancer • Zenker’s Diverticulum

3. 73-year-old woman presents to your office complaining of dysphagia and a 20-lb weight loss during the preceding 6 months. She has a 40 pack-year smoking history, drinks 2 -3 glasses of wine per night, and has had a longstanding history of gastroesophageal reflux disease (GERD) but has not complied with proton pump inhibitor (PPI) therapy. She has had a long standing weight problem (BMI > 35) and current weight loss is not intentional. In her medical record there is a mention of achalasia diagnosed in her 40’s. You suspect that she may have esophageal cancer. In addition to her cigarette smoking and alcohol use, which of her risk factors suggest that she has a squamous-cell carcinoma rather than an adenocarcinoma? • Obesity • GERD symptoms • Noncompliance with PPI therapy • History of achalasia • Older age

4. Dysphagia Motility Structural • As much trouble with liquids as solids • Differential • Achalasia • Scleroderma • Esophageal spasm • Progressive • Solids 1st then liquids • Differential • Schatzki’s Ring • Stricture from damage – GERD, Radiation • Malignancy • Work-up • Barium Swallow • Upper Endoscopy • EUS

5. Achalasia Characterized by: Diagnostic Testing/Treatment • Incomplete relaxation of the LES • Lack of peristalsis in the esophageal body • Often also see a hypertensive LES • Pathologically see ganglionic drop-out at LES • Classic presentation is increasing dysphagia to both liquids and solids with regurgitation • Often with wt loss, chest pain • Testing • Manometry – diagnostic • EGD • Barium Swallow • Treatment • Low Risk Patient – Heller myotomy • High Risk Patient – Botulinum Toxin injection into LES • Pneumatic dilitation

6. Achalasia Endoscopy Dilated, Food Debris Esophageal Manometry Low amplitude, simultaneous contractions, aperistaltic Dilated, Bird’s Beak Plain film – no gastric bubble

7. Esophagitis Clinical Presentation Epidemiology • Most commonly “Heartburn” • substernal chest burning • often accompanied by regurgitation, belching or dysphagia • Specific, not sensitive • Not usually manifested as abdominal pain (dyspepsia) • Sometimes “silent” • Host of other less common symptoms, aka as extra-esophageal symptoms or “atypical” reflux • hoarseness, asthma, chronic cough, sinusitis, bronchitis, bronchiectasis, erosion of dental enamel • App 40% of adult Americans have symptoms of heartburn on a monthly or better basis • 15% with weekly heartburn • Up to 20% of adults have experienced dysphagia • Increases with age • More common in males • Other RF’s - Obesity, Pregnancy, Smoking, Collagen Vasc Dz, EtOH use, Hiatal Hernia

8. Esophagitis Complications Testing • Erosive Esophagitis 10 – 40% • Stricture Formation • Barrett’s Esophagus • Loss of Dental Enamel • Laryngeal Cancer • Aspiration Pneumonia • Pulmonary Fibrosis • Chronic Asthma • Vocal Cord Granulomas • Chronic Sinusitis • Bronchiectasis • Empiric Therapy as a diagnostic test • EGD – good for looking at complications but not as diagnostic of reflux • pH study • 24 hour pH probe • Bravo wireless pH monitoring system • Barium study – good for dysphagia, bad for reflux

9. Endoscopy: Esophagitis Candida Reflux

10. Endoscopy: Strictures/Ring

11. Eosinophilic Esophagitis Clinical Endoscopic Image • Eosinophilic infiltration of the esophagus • Allergic or idiopathic • Main symptom dysphagia • Classic endoscopic features • Rings, furrows, • > 15 eosinophils per hpf despite 1-2 month acid suppression • Treated with swallowed fluticasone

12. GERD Complication: Barrett’s Esophagus • Metaplastic change of mucosa from squamous to specialized columnar • Premalignant condition for adenoCA of esophagus • Risk of cancer is low • Occurs in app 10% of those with weekly GERD • May be asymptomatic • Does not spontaneously resolve • Less symptomatic than nl mucosa • Progression  no dysplasia  low grade dysplasia  high grade dysplasia  cancer Annual surveillance for patients with dysplasia

13. Epidemiology - SCCa vs. Adenocarcinoma SCCa Adenocarcinoma • More common in African-Americans • More common in lower SES • Associated with smoking • Associated with EtOH • Associated with toxic ingestions • More common in Caucasians • Strongly associated with reflux symptoms and the development of Barrett’s esophagus Rare Cancers: 12, 000 yr in US, Equal number squamous and adenocarcinoma

14. Stomach • Gastritis and PUD • Helicobacter Pylori • MALT Lymphoma • ZE Syndrome • Gastric Cancer

15. Pathophysiology of PUD Disease Normal Increased Damage -NSAIDS -H Pylori -Smoking -Alcohol - Hyperacidity • Damaging forces • Gastric Acid • Peptic enzymes Ulcer Defensive Forces -mucus secretion -bicarb secretion -mucosal blood flow -prostaglandins -cellular regeneration -apical surface membrane transport Impaired Defense -Ischemia -Shock -Delayed Gastric Emptying Balance between aggressive and protective forces

16. Helicobacter pylori Clinical Helicobacter • 75 % of DU • 75% of non-NSAID associated gastric ulcers • H pylori enhances gastric acid secretion • Infection occurs prior to ulceration – only 10-15% will develop ulcer disease. • Environmental factors increase risk. • Association with MALT lymphoma • Gram negative bacillus • Produces urease, catalase, LPS and vacuolatingcytotoxin • Colonizes the gastric antrum

17. Eradication of Helicobacter Pylori infection would most likely benefit patients who present with which of the following diseases? • Functional (nonulcer dyspepsia) • Gastric adenocarcinoma • Gastric ulcer • Gastroesophageal Reflux Disease

18. A 45 year old patient with a history of duodenal ulcer and H pylori infection was treated with a 14 day course of lansoprazole, amoxicillin and clarithromycin. One year after therapy, the patient was recurrent symptoms and is found to have another duodenal ulcer by endoscopy and rapid urease testing of an endoscopically-obtained antral mucosal biopsy is positive. He is a nonsmoker and denies use of NSAIDs. Assuming excellent compliance with his prior 14 day course of antibiotic therapy, the most likely cause for the recurrent ulcer is • Reinfection with another strain of H pylori • Reinfection with the original strain of H pylori 3. Unsuccessful eradication of H pylori due to clarithromycin resistance 4. Unsuccessful eradication of H pylori due to amoxicillin resistance 5. Surreptitious NSAID use

19. Ables et al (2007) Am Fam Phys. 75:351-358

21. Intestines • Diarrhea • Classification  secretory, osmotic, motility • Infectious • C difficile colitis • Celiac Disease • Inflammatory Bowel Disease • Crohn’s disease • Ulcerative Colitis

22. Diarrhea Pathophysiology • Osmotic /Malabsorption– osmotic load in the intestine resulting in retention of water in the lumen • Secretory – excess secretion of electrolytes and water into the intestinal lumen • Inflammatory – exudation of fluid and protein from the intestinal mucosa • Motility – rapid transit through the colon

23. Osmotic Diarrhea Mucosal Disease Osmotic Agents in the Lumen • Small Intestine • Celiac Disease • Tropical Sprue • Whipple’s Disease • Colon • Inflammatory bowel disease • Infections • Malabsorption • Pancreatic Insufficiency – enzymes not available to break down food • Small bowel bacterial overgrowth • Exogenous agents • Osmotic laxative • Dietary  sorbitol, fructose, lactose in pts with lactase deficiency

24. Osmotic Diarrhea: Pancreatic Endocrine Insufficiency Etiology Clinical • Malabsorption does not occur until exocrine secretions are decreased by 90% • Causes • Chronic alcoholic pancreatitis • Cystic fibrosis • Pancreatic resection • Strategically placed pancreatic cancer • Somatostatinoma • Stool studies  fat malabsorption • Decrease in fat soluble vitamins D,A,K, and E • May be helped with pancreatic enzyme supplementation.

25. Osmotic Diarrhea: Bacterial Overgrowth Pathophysiology Diagnosis • Decreased transit results in overgrowth of bacteria in the small bowel • deconjugation of bile acids • damage to small bowel mucosa • absorption of vitamin B12 • Causes • Motility disorders, small bowel diverticulae • strictures, post-surgical • Small bowel X-Rays • SBFT • Hydrogen breath test • Sucrose • quantitative culture of fluid from duodenum • empiric trial of an appropriate antibiotic • Xifaxin, tetracycline, ciprofloxacin

26. Secretory Diarrhea • Stimulated secretion of intestinal cells • Usually characterized by substantially elevated stool volumes and associated hypokalemia • This continues despite fasting.

27. Increased Secretion Active Secretion Other • Bacterial Toxins • Vibrio cholerae, clostridium difficile, Escherichia coli O157:H7, shigella • Endocrine Tumors • VIPoma, gastrinoma, carcinoid • Villous adenoma • Inflammatory cell products • Prostaglandins and leukotrienes, platelet activating factor, histamine, serotonin

28. Clostridium Difficile Epidemiology Clinical • C diff colonizes the intestinal tract after normal gut flora have been altered. • One of the most common health-care infections • Significant cause of morbidity and mortality among elderly patients • Up to 50% carriage rate in hospitalized patients. • Watery diarrhea • Range in severity from asymptomatic carrier to severe fulminant disease with toxic megacolon. • Cramping, diarrhea, low grade fever and leukocytosis • C diff toxins in stool  toxins A and B – mutation in toxin A may give false negative EIA

29. Clostridium difficile Endoscopy Treatment • Stop the offending antibiotic • Oral metronidazole or oral vancomycin • Can’t use IV vanco – does not get to the gut – can use IV metronidazole • Toxic dilation with progression  urgent surgical therapy • Recurrent disease in up to 25% Endoscopic findings range from patchy erythema to the classic pseudomembranes

30. A 44 year old woman presents with abdominal pain and anemia. During the work-up a small bowel biopsy was performed and a PAS stain was done. This stain revealed foamy PAS+ macrophages. What is this patients diagnosis? • Whipple’s disease • Chronic Pancreatitis • Zollinger-Ellison syndrome • Celiac Sprue • Eosinophilic Gastroenteritis

31. Histology to Recognize • Whipple’s Disease • Celiac Disease • Giardia • Collagenous Colitis • CMV • Cryptosporidiosis • Eosinophilic Gastroenteritis

33. WEB Path

36. Giardiasis • Sources: contaminated water, fecal-oral transmission. • Incubation: 1 - 4 weeks • Symptoms: sudden onset of explosive watery diarrhea, cramps, nausea, bloating, flatulence • Duration: weeks, relapses are common • Treatment: Metronidazole 250 tid x 5 - 7 days

37. Celiac Disease • Gluten sensitive enteropathy • Incidence is 1 in 133 people in the US • Among people with 1st degree relative with CD – 1 in 22 may have the disease • More common in Down’s syndrome and Turner’s syndrome • Absence of HLA-DQ2 or HLA-DQ8 has a NPV close to 100% • Serologic testing anti-endomesial antibody (EMA) or anti-tissue Tranglutaminase AB (anti-tTGA)

38. Celiac Disease Pathogenesis • Gliadin is absorbed into the lamina propria and presented in conjunction with HLA-DQ2 or HLA-DQ8 cell-surface antigens by antigen-presenting cells, probably dendritic cells, to sensitized T cells expressing the α/ß-cell receptor. • Tissue transglutaminasedeamidatesgliadin peptides, generating acidic, negatively charged residues of glutamic acid from neutral glutamines. Because negatively charged residues are preferred in positions 4, 6, and 7 of the antigen-binding groove of HLA-DQ2, deamidatedgliadin elicits a stronger T-cell response Farrell RJ, Kelly CP in N Engl J Med 2002;346:180-8).

40. Celiac Disease and Dematitis Herpetiformis • 15- 25 % of patients with celiac disease will have DH • IGA deposition in the upper papillary dermis • 90% of DH will have Celiac Disease • Affects elbows, kness, buttocks and back

41. Inflammatory Bowel Disease Ulcerative Colitis Crohn’s Disease • Colon only • Diffuse, contiguous • Mucosal • Non-smoker • Any GI Segment • Focal, asymmetric • Transmural inflammation • Smoker • +/- Perianal • +/- Fistula • +/- Granuloma

42. Etiologic Factors in CD • Genetics • Antigenic triggers • Microbial pathogens • Dietary factors • Autoantigens • Other environmental factors • Smoking • Use of oral contraceptives, NSAIDs? Stenson W. In: Yamada T (ed). Textbook of Gastroenterology. 1999:1775. Sandler et al. In: Kirsner JB (ed). Inflammatory Bowel Disease. 2000: 98.

43. Crohn’s Disease Differential Diagnosis Location and Extent • Primary diseases of the ileum • Neoplasms • Vascular diseases • Infections • Miscellaneous (eg, eosinophilic gastroenteritis) • Right-lower-quadrant inflammatory diseases • Acute appendicitis • Periappendiceal abscesses • Cecal diverticulitis • Tubo-ovarian disorders • Endometriosis 40% Ileocolitis 25% Colitis 30% Ileitis/Jejunoileitis 5% Gastroduodenitis

44. Crohn’s Disease Clinical Presentation Evaluation • Abdominal Pain • Diarrhea • Weight Loss • Growth retardation in children • Fever • Perianal disease • Stool studies to R/O fecal pathogens • Blood studies to include: • CBC (anemia) • CRP or sedimentation rate (elevated in inflammation) • Albumin (drops with increasing disease activity “leaky gut”) • Imaging studies • SBFT, CT, CT enterography • Endoscopy • Colonoscopy with ileal intubation, Capsule endoscopy, EGD for upper symptoms

45. Crohn’s Disease Evaluation CT Enterography SBFT

46. Endoscopic Appearance: CD Punched out colonic ulcer Stricture with ulcer in colon Capsule Endoscopy Linear ulcers in SB Linear serpingenous ulcers in the small bowel

47. Crohn’s Disease Transmural Disease: Wall Thickening of Terminal Ileum Skip Areas

48. Crohn’s Disease: Clinical Features Obstruction Fistulization Inflammation • Pain • Tenderness • Diarrhea • Cramps • Distention • Vomiting • Diarrhea • Damage to skin • Air/feces in urine • Types • Enteroenteric • Enterovesical • Retroperitoneal • Enterocutaneous

49. Crohn’s Disease Perianal Disease

50. Crohn’s Disease: Bile Salt Diarrhea and B12 deficiency • The terminal ileum has specialized receptors for absorbing bile salts and B12. With inflammation or resection of the TI  patient may develop B12 deficiency and bile salt diarrhea (choleretic diarrhea) • Resection > 100cm  Fat malabsorption