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Chapter 8 The diseases of digestive system Slide 2 1.reflux esophagitis Definition: esophageal irritation and inflammation due to reflux of gastric secretions into the esophagus Pathologic changes: Eosinophiles, with or without neutrophils, in the epithelial layer Basal zone hyperplasia Elongation of lamina propria papillae Intraepithelial neutrophils are markers of more severe injury Presentation: heartburn and reguritation Complications: bleeding, stricture, bronchospasm and asthma, barrett esophagus 8.1.1 ESOPHAGITIS Slide 3 2.Barret esophagus Definition: metaplasia of the squamous eosphageal mucosa to a more protective columnar type because of chronic exposure to gastric secretions Cause: gastroesophageal reflux disease Gross: irregular gastroesophageal junction with tongues of red granular mucosa extending up into the esophagus Increased risk of dysplasia and esophageal adenocarcinoma Definition: metaplasia of the squamous eosphageal mucosa to a more protective columnar type because of chronic exposure to gastric secretions Cause: gastroesophageal reflux disease Gross: irregular gastroesophageal junction with tongues of red granular mucosa extending up into the esophagus Increased risk of dysplasia and esophageal adenocarcinoma Slide 4 Esophageal carcinoma Squamous cell carcinoma Epidemiology The most common type of esophageal cancer Males>females; age usually>50 Risk factors Heavy smoking and alchol use Achalasia Plummer-vinson syndrome Tylosis Prior lye ingestion Presentation Often asymptomatic until late in the course Progressive dysphagia Weight loss and anorexia Bleeding Hoarseness or cough (advanced cancers) Diagnosis: endoscopy and biopsy Treatment: surgery Prognosis: poor Squamous cell carcinoma Epidemiology The most common type of esophageal cancer Males>females; age usually>50 Risk factors Heavy smoking and alchol use Achalasia Plummer-vinson syndrome Tylosis Prior lye ingestion Presentation Often asymptomatic until late in the course Progressive dysphagia Weight loss and anorexia Bleeding Hoarseness or cough (advanced cancers) Diagnosis: endoscopy and biopsy Treatment: surgery Prognosis: poor Adenocarcinoma Arises in the distal esophagus Associated with Barrett esophagus and dysplasia Prognosis: poor Slide 5 Slide 6 Slide 7 8.1.2 GASTRITIS Slide 8 inflammation of gastric mucosa acute gastritis pathogens clear acute inflammation (neutrophils ) chronic gastritis autoimmune bilious duodenal secretion reflex HP infection inflammation of gastric mucosa acute gastritis pathogens clear acute inflammation (neutrophils ) chronic gastritis autoimmune bilious duodenal secretion reflex HP infection Slide 9 1.acute gastritis Definition: acute inflammation, erosion, and hemorrhage of the gastric mucosa due to a breakdown of the mucosal barrier and acid-induced injury Etiology: chronic aspirin or NSAID use/ Alcohol use/ Smoking/ Postsurgery/ Burns/ Ischemia/ Stress/ Uremia/ Chemotherapy Presentation Epigastric abdominal pain Gastric hemorrhage, hematemesis, and melena 1.acute gastritis Definition: acute inflammation, erosion, and hemorrhage of the gastric mucosa due to a breakdown of the mucosal barrier and acid-induced injury Etiology: chronic aspirin or NSAID use/ Alcohol use/ Smoking/ Postsurgery/ Burns/ Ischemia/ Stress/ Uremia/ Chemotherapy Presentation Epigastric abdominal pain Gastric hemorrhage, hematemesis, and melena Slide 10 (1) acute irritated gastritis 1 pathogens diet 2 lesions edema, hyperemia, hypersection of mucus, erosion (1) acute irritated gastritis 1 pathogens diet 2 lesions edema, hyperemia, hypersection of mucus, erosion Slide 11 (2) acute hemorrhagic gastritis 1 pathogens: medicines ( aspirin )/alcoholism 2 lesion: usually in fundus and body (2) acute hemorrhagic gastritis 1 pathogens: medicines ( aspirin )/alcoholism 2 lesion: usually in fundus and body Slide 12 (3) acute corrosive gastritis 1 pathogen engulf acid/ base 2 lesion stomach wall necrosis perforation (3) acute corrosive gastritis 1 pathogen engulf acid/ base 2 lesion stomach wall necrosis perforation Slide 13 (4) acute infective gastritis 1 pathogens: purulent bacterium 2 lesions: acute phlegmonous inflammation (4) acute infective gastritis 1 pathogens: purulent bacterium 2 lesions: acute phlegmonous inflammation Slide 14 2. chronic gastritis chronic mucosal inflammatory changes leading eventually to mucosal atrophy and epithelial metaplasia. Pathogenesis HP chronic infection chronic irritation autoimmune reflex of bilious duodenal secretion 2. chronic gastritis chronic mucosal inflammatory changes leading eventually to mucosal atrophy and epithelial metaplasia. Pathogenesis HP chronic infection chronic irritation autoimmune reflex of bilious duodenal secretion Slide 15 Slide 16 Slide 17 (1) chronic superficial gastritis (CSG) common glands in lamina propria intact, lymphocyte/plasma infiltrate in shallow mucosa (1) chronic superficial gastritis (CSG) common glands in lamina propria intact, lymphocyte/plasma infiltrate in shallow mucosa Slide 18 (2) chronic atrophic gastritis (CAG) gross mucosa thin, folds flatten LM within mucosa: lymphocyte, plasma cells infiltrate, aggregate, lymph follicle form mucosal proper glands (gastric glands,cardiac glands, pyloric glands atrophy or disappear, dilate intestinal metaplasia (replacement of gastric epithelium with columnar and goblet cells of intestinal-type), pseudopyloric metaplasia (2) chronic atrophic gastritis (CAG) gross mucosa thin, folds flatten LM within mucosa: lymphocyte, plasma cells infiltrate, aggregate, lymph follicle form mucosal proper glands (gastric glands,cardiac glands, pyloric glands atrophy or disappear, dilate intestinal metaplasia (replacement of gastric epithelium with columnar and goblet cells of intestinal-type), pseudopyloric metaplasia Slide 19 chronic atrophic gastritis (CAG) loss of rugal folds in the body and fundus Slide 20 Slide 21 chronic atrophic gastritis Slide 22 Persisting glands frequently undergo cystic dilation Slide 23 Variable gland loss and mucosal atrophy, lymphocyte and plasma cell infiltration in the lamina propria. Intestinal metaplasia replacement of gastric epithelium with absorptive and goblet cells of intestinal-type Slide 24 Slide 25 Fundic type (type A) Antral type type B) Autoimmune atrophic gastritis rare Involve the body and fundus Autoantibodies to parietal cells / intrinsic factor Loss of parietal cells Decreased acid secretion Increased serum secretion ( G cell hyperplasia) Pernicious anemia (megaloblastic anemia due to lack of intrinsic factor and B12 malabsorption) Helicobactor pylori gastritis Common Helicobactor pylori Curved, gram negative rods Urease producing Risk of infection increase with age Associated with chronic gastritis (type B) Associated with duodenal / gastric peptic ulcers Associated with gastric carcinoma Gross: loss of rugal folds in the body and fundus Micro: mucosal atrophy with loss of glands and parietal cells Chronic lymphoplasmacytic inflammation Intestinal metaplasia Micro: foci of acute inflammation Chronic inflammation with lymphoid follicules Intestinal metaplasia Increased risk of gastric carcinoma Slide 26 8.1.3 peptic ulcer Ulcer: defects in the mucosa that penetrate at least into the submucosa, and often into the muscularis propria or deeper Definition: ulcers of the distal stomach and proximal duodenum caused by gastric secretion (hydrochloric acid and pepsin) and impaired mucosal defenses Diagnosis: endoscopy biopsy Treatment: acid suppression (H2 blocker, proton pump inhibitor) eradication of H. pylori Complications: hemorrhage: 1/3 common, hematemesis, melena, shock iron deficiency anemia penetration into adjacent organs: 5%, acute diffuse peritonitis, local peritonitis perforation (X-ray: free air under the diaphragm) pyloric obstruction : 2- 3% gastric ulcer: 1%; duodenal ulcer: no 8.1.3 peptic ulcer Ulcer: defects in the mucosa that penetrate at least into the submucosa, and often into the muscularis propria or deeper Definition: ulcers of the distal stomach and proximal duodenum caused by gastric secretion (hydrochloric acid and pepsin) and impaired mucosal defenses Diagnosis: endoscopy biopsy Treatment: acid suppression (H2 blocker, proton pump inhibitor) eradication of H. pylori Complications: hemorrhage: 1/3 common, hematemesis, melena, shock iron deficiency anemia penetration into adjacent organs: 5%, acute diffuse peritonitis, local peritonitis perforation (X-ray: free air under the diaphragm) pyloric obstruction : 2- 3% gastric ulcer: 1%; duodenal ulcer: no Slide 27 Damaging factors Peptic acid pepsin Normal mucosa Defensive factors Surface mucus secr. HCO- into mucus Mucosal blood flow Epithelia regenera PG Epithelial barrier Increased damage HPNSAIDssmokingalcohol gas. acidity Duo-gast.reflux Peptic ulcer healin g Impaired defenses ischeriashockDelayed gastric empty hemorrhage p.stenosis Malignant t. 2)Pathogenesis of peptic ulcer NSAIDs perforation Slide 28 Slide 29 Slide 30 Slide 31 gastric ulcer Associated with H. pylori (75%) Location: lesser curvature of the antrum Gross: small ( Gross Large (>2cm), irregular ulcer Heaped-up margins and a necrotic ulcer base May also occur as a flat or polypoid mass Metastasis Virchow (sentinel) node: left supraclavicular lymph node Krukenberg tumor: spread to the ovary Diagnosis: endoscopy and biopsy Treatment: gastrectomy Prognosis: poor; over all 5-year survival 20% Gross Large (>2cm), irregular ulcer Heaped-up margins and a necrotic ulcer base May also occur as a flat or polypoid mass Metastasis Virchow (sentinel) node: left supraclavicular lymph node Krukenberg tumor: spread to the ovary Diagnosis: endoscopy and biopsy Treatment: gastrectomy Prognosis: poor; over all 5-year survival 20% Slide 45 Intestinal type micro: gland-forming adenocarcinoma Diffuse type diffuse infiltration of stomach by poorly differentiated tumor cells signet-ring cells: nucleus is displaced to the periphery by intracellular mucin linitis plastica: thickened leather bottle-like stomach Intestinal type micro: gland-forming adenocarcinoma Diffuse type diffuse infiltration of stomach by poorly differentiated tumor cells signet-ring cells: nucleus is displaced to the periphery by intracellular mucin linitis plastica: thickened leather bottle-like stomach Slide 46 Slide 47 pathologic change (1) early gastric car. (shallow spread car. concept confined to the mucosa and submucosa, regardless of the size of area, or absence of perigastric lymph node metastasis pathologic change (1) early gastric car. (shallow spread car. concept confined to the mucosa and submucosa, regardless of the size of area, or absence of perigastric lymph node metastasis Slide 48 9-10 2 gross types protruded type (type ) >2 times thickness gastric mucosa, polypoid superficial type (type ) superficial elevated type a < 2 times thickness superficial flat type b superficial depressed c depth within mucosa excavated type (type ) common, ulcer Slide 49 Slide 50 Slide 51 Slide 52 Slide 53 3 histologic types tubular adenocarcinoma> papillary adenocarcinoma> undifferentiated carcinoma 3 histologic types tubular adenocarcinoma> papillary adenocarcinoma> undifferentiated carcinoma Slide 54 (2) advanced gastric carcinoma concept extended below the submucosa into the muscular wall and has perhaps spread more widely gross polypoid or fungating type ulceration type erosive crater, D>2.5cm infiltrating type: Linitis plastica (2) advanced gastric carcinoma concept extended below the submucosa into the muscular wall and has perhaps spread more widely gross polypoid or fungating type ulceration type erosive crater, D>2.5cm infiltrating type: Linitis plastica Slide 55 Slide 56 3 histologic types papillary adeno. tubular adeno., mucous adeno., signal cell car., undifferentiated car. Lauren intestine type, diffuse type 3 histologic types papillary adeno. tubular adeno., mucous adeno., signal cell car., undifferentiated car. Lauren intestine type, diffuse type Slide 57 Slide 58 Slide 59 fungating type Slide 60 Slide 61 Slide 62 Slide 63 Slide 64 ulceration type (the ulcer is large with irregular, heaped- up margins. There is extensive excavation of the gastric mucosa with a necrotic gray area in the ddepest portion. Slide 65 ulceration type Slide 66 infiltrating type (a broad region of the gastric wall, or the entire stomach, is extensively infiltrated by maglinancy. The rigid and thickened stomach is termed a leather bottle stomach, or linitis plastica.) Slide 67 Gastric adenocarcinoma (gland formation by malignant cells, which are invading the muscular wall of the stomach.) Slide 68 Gastric mucous adenocarcinoma Slide 69 Gastric signet cell carcinoma (permeate the mucosa and wall as scattered individual signet-ring cells or in small clusters.) Slide 70 Gastric undifferentiated carcinoma Slide 71 4 spread pathways direct spread liver, pancreas lymphatic metastasis main pathways Virchow lymph nodes hematogenous metastasis liver/ lung/ bone/ brain seeding abdominal cavity, peritonaeum, ovary Krukenberg tumor 4 spread pathways direct spread liver, pancreas lymphatic metastasis main pathways Virchow lymph nodes hematogenous metastasis liver/ lung/ bone/ brain seeding abdominal cavity, peritonaeum, ovary Krukenberg tumor Slide 72 Slide 73 Slide 74