Diseases of the Stomach PDF

Diseases of the Stomach WE MAKE DOCTORS  OBJECTIVES Apply knowledge of GI anatomy, histology, and physiology to explain the clinicopathologic features, diagnostic criteria, and therapy of disorders resulting in inflammation, infection and u...

Diseases of the Stomach WE MAKE DOCTORS  OBJECTIVES Apply knowledge of GI anatomy, histology, and physiology to explain the clinicopathologic features, diagnostic criteria, and therapy of disorders resulting in inflammation, infection and ulcerations. Describe the pathophysiology and clinicopathological features of acute and chronic gastritis. Identify the features of Pylori infection and relate it to gastric pathology. Define PUD, recognize the differences between duodenal and gastric ulcers, identify their risk factors and clinical course.  Acute Gastritis Gastropathy Inflammation of gastric Dysfunction of the stomach mucosa Absent inflammatory cells Presence of neutrophils NSAIDs, alcohol, and bile are common causes. Signs & symptoms Asymptomatic Epigastric pain Nausea/vomiting Mucosal erosion Ulceration Hemorrhage Melena Gastritis Gastric Ph = 1 Foveolar cells produce mucus and phospholipids Neutral Ph fluid = alkaline tide for epithelial protection NSAID, Cox and Prostaglandins (E and I)decrease Ph Uremia or H. Pylori (urease) =Increase ammonium levels and decrease H3CO2 Lamina propria: edema and vascular congestion cause foveolar edema (corkscrew profile). Erosion (loss of mucosa) with neutrophils, pus, and fibrin = hemorrhagic erosive gastritis.  Morphology Gastritis Gastropathy Neutrophils above the Hyperplasia of foveolar basement membrane in mucus cells is typically contact with epithelial cells present is abnormal in all parts of The surface epithelium is the gastrointestinal tract intact Signifies active Neutrophils, lymphocytes, inflammation à gastritis and plasma cells are not prominent Mechanisms of injury Inhibition of cyclooxygense (COX) by NSAIDs. NSAIDs inhibit COX-dependent synthesis of prostaglandins E 2 and I 2 Affect all protective barriers They also reduce acid secretion. The risk of NSAID-induced gastric injury is greatest with nonselective inhibitors but COX-2 inhibitors can also cause gastropathy or gastritis. Inhibition of gastric bicarbonate transporters by ammonium ions (uremia and urease-secreting H. pylori) Reduced mucin and bicarbonate secretion suggested for older adults gastritis. Decreased oxygen delivery may account for an increased incidence of acute gastritis at high altitudes or any hypoxic condition. Gastritis Gastropathy Erosive Gastritis NSAIDs Hypoxia Stress-Related Mucosal Disease Occurs in patients with: Severe trauma Extensive burns Intracranial disease Major surgery Any kind of severe physiological stress More than 75% of critically ill patients develop endoscopically visible gastric lesions during the first 3 days of their illness Stress-Related Mucosal Disease Stress ulcers Presents in critically ill patients with shock, sepsis, or severe trauma Curling ulcers Occurs in the proximal duodenum, associated with severe burns or trauma Cushing ulcers Occurs in the stomach, duodenum, or esophagus, associated with intracranial disease Presents with a high incidence of perforation Stress-Related Mucosal Disease Pathogenesis: It is usually due to local ischemia Caused by systemic hypotension or reduced blood flow Increased release of the vasoconstrictor endothelin-1 also contributes to gastric ischemia Cushing ulcers are thought to be caused by direct stimulation of vagal nuclei à results in acid hypersecretion Systemic acidosis also contributes to mucosal injury by lowering the intracellular pH of mucosal cells Chronic Gastritis HELICOBACTER PYLORI Autoimmune atrophic 10%, biliary reflux, mechanic Ulcerative lesion, (vs Crohn’s disease) Nausea, epigastric pain. Colonization vs. Infection If in antral = duodenal ulcer If body or fundus = multifocal atrophic ↓ parietal cells ↓ acid = intestinal metaplasia and risk of gastric cancer. Citation: Chapter 163 Helicobacter pylori Infections, Loscalzo J, Fauci A, Kasper D, Hauser S, Longo D, Jameson J. Harrison's Principles of Internal Medicine, 21e; 2022. Available at: https://accessmedicine.mhmedical.com/content.aspx?bookid=3095&sectionid=265422379 Accessed: June 14, 2023 Copyright © 2023 McGraw-Hill Education. All rights reserved Helicobacter Pylori Gastritis Pathogenesis: Four features are linked to H. pylori virulence: 1. Flagella à allows the bacteria to be motile in viscous mucus 2. Urease à generates ammonia. This elevates local gastric pH around the organisms and protects the bacteria from the acidic pH of the stomach 3. Adhesins à increase bacterial adherence to surface foveolar cells 4. Toxins à these may be involved in ulcer or cancer development (E.g., cytotoxin-associated gene A à CagA) Helicobacter Pylori Gastritis Morphology: Gastric biopsy Higher concentration of mucus overlying epithelial cells in the surface and neck regions Presence of neutrophils within the lamina propria (pit abscesses) The superficial lamina propria includes large numbers of plasma cells and increased presence of lymphocytes and macrophages< Helicobacter Pylori Gastritis Pyloric glands are infiltrated by Gastric gland reveals infiltration neutrophils, and increased numbers with neutrophils of chronic inflammatory cells are in the lamina propria Helicobacter Pylori Gastritis Helicobacter pyloribacteria can be identified on hematoxylin and eosin stains, as shown in the circle. Other H pylori forms are also seen elsewhere in the picture, albeit more sparsely. The bacteria characteristically are adherent to the surface of the gastric epithelial cells or within the mucus layer that lines the luminal surface of the gastric mucosa. Helicobacter Pylori Gastritis Biopsy of gastric antral mucosa of patient with Helicobacter pylori- associated chronic active gastritis. Note the presence of superficially oriented inflammation, including chronic inflammation (plasma cells and lymphocytes) and acute inflammation (neutrophils). The presence of neutrophils in the mucosa, with neutrophil permeation into and through the gastric epithelium indicates active disease (B: inset). H pylori bacteria are seen adherent to the surface of gastric epithelial cells, as minute linear to punctuate purple forms (arrow).  Helicobacter Pylori Gastritis Morphology: Intense, inflammatory infiltrates may create thickened rugal folds Lymphoid aggregates, This represents an induced form of mucosa-associated lymphoid tissue (MALT) It may lead to lymphoma Follicular lymphoid hyperplasia associated with prominent chronic gastritis. An enlarged lymphoid follicle with germinal center is present Helicobacter Pylori Gastritis Intestinal metaplasia is characterized by the presence of goblet cells and columnar absorptive cells When present, it is associated with increased risk of gastric adenocarcinoma Numerous goblet cells à confirms the Periodic acid-Schiff stain diagnosis of intestinal metaplasia highlights the goblet cells Autoimmune Gastritis It is characterized by: Less than 10% of cases of chronic gastritis Spares antrum and induces marked hypergastrinemia Antibodies to parietal cells and intrinsic factor in serum and gastric secretions Reduced serum pepsinogen I levels (chief cell loss) Antral endocrine cell hyperplasia Vitamin B 12 deficiency à pernicious anemia Impaired gastric acid secretion à achlorhydria H. Pylori Gastritis vs. Autoimmune Gastritis Autoimmune Gastritis Autoimmune = loss of parietal cells ↓ acid and intrinsic factor. Hypergastrinemia = G cells hyperplasia ↓ vitamin B12 absorption= megaloblastic (pernicious) anemia Chief cell destruction ↓ pepsinogen I CD4 to components, included H+,K+atpasa. Treatment is directed to protect gastric stem cells which in turn will differentiate into chief and parietal Autoimmune Gastritis Morphology: Diffuse damage of the oxyntic (acid- producing) mucosa in body and fundus characterizes this pathology Inflammatory infiltrate of lymphocytes, macrophages, and plasma cells Parietal and chief cell loss can be extensive, and intestinal metaplasia may develop Chronic Gastritis Epithelial lamina propria contains plasmocytes in clusters or sheets Thickened folds could look like precancerous lesions Lymphoid aggregates, with germ centers are a form of lymphoid tissue in the mucosa with the possibility to turn into MALT lymphoma Chronic Gastritis Epigastralgia, yields or decreases with food Stomach emptiness sensation Nausea or vomiting in cases of flare-ups. Generally associated with esophagitis, Indirect testing, endoscopy with lesion, and biopsy Breath test Complications: Peptic ulcer disease, mucosal atrophy, intestinal metaplasia, dysplasia GASTRIC ANTRAL METAPLASIA Hypertrophic Gastropathies Uncommon diseases. Giant cerebriform enlargement of rugal folds Epithelial hyperplasia without inflammation (increased growth factor release PARAMETER MENETRIER DISEASE (ADULT) ZOLLINGER-ELLISON SYNDROME Mean patient age 30 – 60 50 Location Body and fundus Fundus Predominant cell type Mucous Parietal>mucous, endocrine Inflammatory infiltrate Limited, lymphocytes Neutrophils Symptoms Hypoproteinemia, weight loss, Peptic ulcers diarrhea Risk factors None Multiple endocrine neoplasia Association with yes No adenocarcinoma Hypertrophic Gastropathies Foveolar hyperplasia with elongated and focally dilated glands Zollinger-Ellison Syndrome Gastrin-secreting neuroendocrine tumors Gastrinomas in the small intestine or pancreas Solitary lesions ibn 75% of patients 25% MEN I Duodenal ulcers or chronic diarrhea Marked increase in oxyntic mucosa thickness due to massive parietal cell hyperplasia Peptic Ulcer Disease Chronic mucosal ulceration in duodenum or stomach associated mostly with H. pylori infection, NSAIDs, or smoking. Gastric antrum and duodenum due to increased gastric acid secretion and decreased duodenal bicarbonate secretion. Gastric fundus or body has modest increase in acid secretion from associated atrophy, which protects from antral or duodenal. Ectopic gastric mucosa in duodenum, Meckel diverticulum, or esophageal ectopic mucosa may also cause PUD Peptic Ulcer Disease: Risk factors Helicobacter Pylori Smoking Psychologic stress COPD Parietal cell hyperplasia Hard drugs (cocaine) Zollinger-Ellison NSAIDs (corticosteroid syndrome enhanced) Viral Infection (CMV, Alcoholic cirrhosis herpes) (duodenal) Peptic Ulcer Disease: Risk factors Helicobacter Pylori Smoking Psychologic stress COPD Parietal cell hyperplasia Hard drugs (cocaine) Zollinger-Ellison NSAIDs (corticosteroid syndrome enhanced) Viral Infection (CMV, Alcoholic cirrhosis herpes) (duodenal) Polyps Over 75% hyperplasic or inflammatory (H. Pylori) 5-6 years of chronic or reactive = if 1.5cm resectable Multiple, ovoid, smooth surface or eroded Fundus glands due to familial adenomatosis Increased by pump inhibitors – dysplasia and cancer, 10% of polyps are adenomatous, more common in males 30% become malignant Solitary, less than 2cm, antral. Gastric Cancer ADENOCARCINOMA Most frequent malignant tumor in stomach Intestinal type= large masses, penetrated, exofitic and ulcerated presentation Diffuse type = infiltrative, thickened (Signet ring cells) Most in antrum and lesser curvature. Dispepsia, dysphagia, nausea Weight loss, anorexia, early satiety, anemia and hemorrhage Japan, Chile, Costa Rica and East Europe = 20 fold more frequent Gastric Cancer More common in low socioeconomic level (associated to H.Pylori infections) Dysplasia and adenomas are precursor lesions Ulcers = no higher incidence Common sites of metastasis (sometimes the form of diagnosis) Metastasis to sentinel node ( Virchow) Periumbilical (sister Mary Joseph) Left axillary (irish) Ovaric ( Krukenberg) Douglas pouch (Blumer sign) Gastric Carcinoma Decrease incidence with decrease intake of alimentary factors, (Nitrates, Benzopirene) Loss of function of CDH1 = cadherin E (in familial cases and up to 50% of diffuse type) Intestinal type have increased signaling of Wnt. Loss of function of APC (suppressor) Gain of function in B-catenin expression TGF-B signaling BAX regulation of apoptosis CDKN2 cell cycle control Proinflammatory IL-1β and IL-1 increase the risk (H. pylori) Gastric Carcinoma Apical mucine vacuoles Desmoplastic reaction= rigid wall = leather bag from linitis plastica. Surgical resection = total or subtotal gastrectomy survival of 90% Advanced less than 20% Gastric Adenocarcinoma Gastric Carcinoma Poorly cohesive carcinoma, including signet ring cell carcinoma Neoplastic cells that are isolated or arranged in small aggregates without well-formed glands Signet ring cells are characterized by a central, optically clear, globoid droplet of cytoplasmic mucin with an eccentrically placed nucleus There is low risk of nodal metastasis for intramucosal signet ring cell carcinoma Gastric Lymphoma Bibliography Robbins And Cotran Pathologic Basis Of Disease, Ninth Edition. Vinay Kumar MBBS, MD, FRCPath; Abul K. Abbas MBBS; Jon C. Aster MD, PhD: Copyright © 2015 by Saunders, an imprint of Elsevier Inc: Chapter 17, The Gastrointestinal Tract Harrison. Principios de Medicina Interna, 19e Dennis Kasper, Anthony Fauci, Stephen Hauser, Dan Longo, J. Larry Jameson, Joseph Loscalzo