Gastrointestinal Tract

1. Gastrointestinal Tract

2. Gastrointestinal Tract

3. Stomach Glands: Parietal cells found in fundus and body Secrete HCl & intrinsic factor Chief cells are more at fundus and body Secrete pepsinogen I & II Congenital Anomalies 1. Diaphragmatic Hernia: A defect in the diaphragm ? away from the hiatal orifice (not hiatal hernia) Portions of stomach & small intestine herniates Results in respiratory impairment & pulmonary hypoplasia

4. Stomach - Normal

5. Stomach - Normal

6. Stomach . 2. Congenital Hypertrophic Pyloric Stenosis: Hypertrophy of the circular muscle of the pylorus Results in Regurgitation & vomiting in the neonatal period VGP-visible Gastric peristalsis & palpable mass in the epigastrium males, multifactorial inheritance. Rx: A full thickness muscle splitting incision (pyloro-myotomy) is curative (Heller�s operation)

7. Stomach - Normal

8. Stomach Acute Gastritis= inflammation of gastric mucosa acute � presence of neutrophils Chronic �lymphocytes and plasma cells Caused by ingestion of strong acids or alkalies, NSAIDs, cancer chemotherapy, irradiation, alcohol, uremia, severe stress & shock states Proposed mechanisms: ? acid production with ? surface bicarbonate buffer Morphology: Mucosal edema, hyperemia, PML infiltration, erosions (not deeper than muscularis mucosa) & hemorrhages

9. Acute Gastritis Gastric mucosa demonstrates infiltration by Neutrophils

10. Acute Gastritis diffusely hyperemic gastric mucosa causes for acute gastritis alcoholism drugs infections, etc.

11. Stomach Chronic Gastritis = Chronic mucosal inflammation Leading to mucosal atrophy, intestinal metaplasia & dysplasia. Pathogenesis: Chronic infection by Helicobacter pylori (90%): MCC of chronic gastritis, Elaboration of urease ? produces ammonia that buffers gastric acid, protecting organism from acid Other diseases associated with H. pylori Infection Peptic ulcer disease Gastric carcinoma Gastric lymphoma Autoimmunity (>10%): Antibodies to parietal cells cause parietal cell destruction (HCl & intrinsic factor)

12. Stomach Chronic Gastritis Morphology: Autoimmune ? diffuse mucosal damage of the body-fundic mucosa H. pylori ?affect antral mucosa Histology: Lymphocytic & plasma cell infiltrate of the lamina propria atrophy, regeneration, metaplasia (to intestinal type mucosa) & dysplasia. H. pylori detected on the mucosal surface Clinically: Mild abdominal discomfort, nausea, vomiting; hypochlorhydria, hypergastrinemia & rarely Overt pernicious anemia (in autoimmune) gastritis). Long-term risk of cancer is 2-4%

13. H. pylori small curved to spiral rod-shaped bacterium is found in the surface epithelial mucus of most patients with active gastritis The rods are seen here with a methylene blue stain.

14. Autoimmune gastritis Autoimmune gastritis - pernicious anemia Chronic atrophic gastritis is associated with Ab�s - intrinsic factor - patietal cell bright green IF- in the parietal cells of the gastric mucosa.

15. Stomach Peptic Ulcer Disease Ulcer - a breach in mucosa & extends thru muscularis mucosae into submucosa or deeper 1) Acute Gastric Ulcers: acute erosive gastritis = erosions ABOVE the muscularis mucosa Caused by Severe stress (= Stress Ulcers) Shock, extensive burns (Curling�s ulcers) Severe head injuries (Cushing�s ulcers) patients in Intensive Care Units, use of NSAIDs. Morphology: Multiple, small (<1 cm) ulcers, normal adjacent mucosa Clinically: Upper GIT hemorrhage. Treatment: treat underlying cause

16. Stress ulcers small, shallow gastric ulcerations known as "stress ulcers" patients with a variety of stressful conditions, including trauma, burns, sepsis, and shock. Anti-inflammatory drugs such as aspirin and NSAIDs may play a role in their appearance.

17. 2) Peptic ulcers - chronic Characterized by: Solitary, chronic ulcers, Ratio of duodenal : gastric = 4 : 1 (Duodenal ulcer is more common) Morphology: Sharply punched out mucosal defect With sharp borders & clean ulcer base. Surrounding mucosa shows chronic gastritis & radial convergence of rugal folds towards the ulcer niche (unlike malignant ulcer) Clinically: Epigastric pain 1-3 hours after meals & worse at night; nausea; vomiting; belching & occult blood in the stools. Complications: Perforation - accounts for ~ 2/3rds of ulcer deaths Hemorrhage - accounts for 25% of ulcer deaths Obstruction - causes severe crampy abdominal pain Malignant transformation is extremely rare

18. Peptic Ulcerpathogenesis

19. Gastric ulcer larger 3 x 4 cm gastric ulcer This ulcer is much deeper with more irregular margins Complications of gastric ulcers (either benign or malignant) include pain Bleeding (MC) Perforation (most dangerous) obstruction.

20. Gastric ulcer Microscopically the ulcer here is sharply demarcated, with normal gastric mucosa on the left falling away into a deep ulcer whose base contains inflamed, necrotic debris Arterial branch at the ulcer base is eroded and bleeding.

21. 3). Hypertrophic Gastropathy Characterized by Giant enlargement of the gastric rugal folds Caused by hyperplasia of epithelial cells ( not due to inflammation ) ?risk of cancer Includes 3 variants A) Menetrier�s disease Hyperplasia of surface mucous cells glandular atrophy excessive loss of proteins in gastric secretion (protein-losing Gastropathy) B) Hypersecretory Gastropathy Hyperplasia of parietal and chief cells Secondary to excessive gastrin stimulation. C) Zollinger - Ellison Syndrome Caused by Gastrinoma of Pancreas secreting gastrin ? elevated serum gastrin levels multiple peptic ulcerations in stomach, duodenum, jejunum Hypertrophic rugal folds & Parietal cell hyperplasia ? excess gastric acid production

22. Benign Tumors of the stomach: 1) Gastric polyps Most of the polyps ( 90%) are non-neoplastic polyps (hyperplastic &/or inflammatory) no malignant potential. Gastric polyps must be biopsied 2) Adenomatous Polyps true neoplasms with proliferative dysplastic epithelium Have malignant potential, common in old age MC associated with chronic gastritis or familial polyposis syndromes

23. Malignant - Tumors 1. Gastric Carcinoma Incidence: 4-fold decline in incidence over the last 70 years (for unknown reasons). Risk Factors: Diet: Nitrites (from food preservatives), smoked and salted foods, deficiency of fresh fruits and vegetables. Host Factors: Chronic gastritis (autoimmune & H. pylori), Adenomatous polyps, partial gastrectomy pts. Genetic Factors: blood group A, close relatives of stomach cancer patients, certain racial groups (Japanese) Classification: A) Early Gastric Carcinoma: Confined to the mucosa & submucosa, despite lymph node spread Associated with very good prognosis (>90% 5-year survival)

24. B) Advanced Gastric Carcinoma: Has extended beyond the submucosa & Spread is by local invasion, lymphatics, blood (to liver & lungs) Krukenberg tumor = bilateral ovarian metastases (stomach, breast, pancreas, and even gallbladder ) Virchow node= left supraclavicular node with mets. Sister Mary Joseph nodule = metastasize to the periumbilical region (subcutaneous malignant nodule) Histologic types: Intestinal type, glandular, expansile growth pattern Gastric type, diffuse �signet ring� infiltrating pattern Pathologic stage is the most important prognostic indicator 2) Gastrointestinal Stromal Tumor (GISTs) Arise from Interstitial cells of Cajal c-KIT (CD117) & CD34- positive

25. 3. Carcinoid (neuroendocrine) tumors made of Enterochromaffin-like (ECL) cell tumors Associated with multiple endocrine neoplasia type 1 (MEN1) & Zollinger-Ellison syndromes 4) Gastric Lymphoma MC site for extranodal lymphoma majority (>80%) are associated with H. pylori chronic gastritis

26. Stomach gastric carcinoma Gastric adenocarcinoma in the U.S., most gastric cancers are discovered at a late stage when the neoplasm has invaded and/or metastasized. All gastric ulcers and All gastric masses must be biopsied, In contrast, virtually all duodenal peptic ulcers are benign.

27. Stomach gastric carcinoma Malignant gastric ulcer This ulcer on biopsy proved to be malignant, so the stomach was resected

28. Linitis plastica a diffuse infiltrative gastric adenocarcinoma stomach looks like a shrunken "leather bottle" appearance markedly thickened gastric wall very poor prognosis.

29. Case - 1 A 48-year-old man has had vague abdominal discomfort for a number of years. There is no history of hematemesis, but he has occasional nausea and vomiting. An upper GI endoscopy is performed. There is no evidence for ulceration or a mass lesion, and gastric biopsies are taken. Images 8.1 and 8.2 demonstrate the gastric mucosa at low and high magnification. The surface of the gastric mucosa at high magnification is seen in images 8.3 and 8.4.

30. 1.1

31. 1.2

32. 1.3

33. 1.4

34. Case - 2 A 55-year-old woman, with a history of epigastric pain relieved by food, complained of episodes of hematemesis that have occurred in the past week. Upper GI endoscopy with biopsies was performed (image 3.1). The specimen shown here is from the subsequent partial gastrectomy (image 3.2). The lesion appears as a cup-shaped ulcer filled with blood clot. The ulcer, which was found to extend almost through the gastric wall, is lined by necrotic debris and acute inflammatory cells overlying a base of granulation tissue and fibrosis (images 3.3 and 3.4) with a large vessel at the base (image 3.5).

35. 2.1

36. 3.2

37. 3.3

38. Case -3 A 60-year-old man complained of anorexia, vomiting, and vague abdominal pain accompanied by weight loss of 15 kg over the past two months. Physical examination revealed supraclavicular lymphadenopathy. An abdominal CT scan revealed that the stomach wall was thickened . He became progressively cachectic and died. At autopsy, the stomach was diffusely thickened and leather-like . Microscopic sections of the gastric wall are shown .

39. 3.1

40. 3.2

41. 3.3