Diseases Of Gastrointestinal System (PDF)

DISEASES OF GASTROINTESTINAL SYSTEM Part I & II NB2244 NOR MALIA ABD WARIF Ѳ [email protected]  OVERVIEW OF GIT Esophagus Stomach Food , water Small intestine Colon Appendix...

DISEASES OF GASTROINTESTINAL SYSTEM Part I & II NB2244 NOR MALIA ABD WARIF Ѳ [email protected]  OVERVIEW OF GIT Esophagus Stomach Food , water Small intestine Colon Appendix NB2244 2 LECTURE OUTLINE To explain the aetiology, pathogenesis, clinical symptoms, method of diagnosis and histopathological changes that occur in the : (Lecture 1)  Esophagus : esophagitis and cancer of esophagus  Stomach : congenital pyloric stenosis, gastritis, peptic ulcer, gastric cancer NB2244 (Lecture 2)  Small intestine and colon : Crohn’s disease, ulcerative colitis and colon cancer  Appendix : appendicitis 3 Overview : Disease of Esophagus Congenital Disorder Hiatal Hernia Esophagitis Reflux Esophagitis Eosinophilic Esophagitis Barrett Esophagus NB2244 Esophageal Tumors Squamous cell carcinoma Adenocarcinoma 4 INFLAMMATION OF THE ESOPHAGUS : ESOPHAGITIS Inflammation of the lining (stratified squamous mucosa) of esophagus; commonly occurs due to reflux. opposite ~ direction maybe damaged by chemical(irritant) or microbial infection Major complication (untreated) : narrowing ulcer, bleeding , stricture, Barrett esophagus (rare type) acid enter esophagous Common types : L Stomach NB2244 reflux esophagitis (GERD) - ↓ eosinophilic esophagitis - allergic damage esophagous living Incidence : reaction 5% to 11% incidence in US, although reflux symptoms in 33 - 44% of general population Higher incidence in northern Iran and China 5  …..Esophagitis ETIOLOGY Irritation caused by alcohol, excessively hot fluids, spicy food and heavy smoking hakisar corrosive acids or alkalis (reflux of gastric contents) medication (aspirin), large pill swallowing toxic substance - Graft-versus- radiation therapy, cytotoxic chemotherapy, GVHD host-diseas hiatal hernias – opening in diaphragm at esophagus-stomach join > lead to NB2244 - reflux Infection In weak immune system eg. diabetes, HIV, undergoing chemotherapy, on antibiotics. Bacteria (Helicobacter) Viral (Herpes, Cytomegalovirus) Fungi/yeast (Candida) 6  …..Esophagitis CLINICAL SYMPTOMS susahtelan Difficult (dysphagia) and/or painful swallowing Heartburn Burning sensation in esophagus Feeling of something stuck in throat NB2244 Mouth sores, bad breath (halitosis) Blood in vomit (hematemesis) – less common, severe condition 7  …..Esophagitis REFLUX ESOPHAGITIS Developed when gastric contents are passively regurgitated into esophagus dimuntankar related to hiatal hernia and lower esophageal sphincter Commonly happens (after a meal) Does not cause major harm Clearance of refluxate back to stomach by natural NB2244 peristalsis Persistant reflux damaged esophagus leads to inflammation, erosion and ulceration of esophageal mucosa 8  …..Esophagitis EOSINOPHILIC ESOPHAGITIS Chronic immunologically mediated disorder : related to histamine released from sensitized mast cells in the esophageal wall epithelial infiltration by large numbers of eosinophils Corrugated (wrinkled) esophagus Characterized by concentric mucosal ring NB2244 leads to acetylcholine release that contracts muscle fibers in muscularis mucosa forming rings. Intraepithelial eosinophils 9  …..Esophagitis LAB DIAGNOSIS Upper GI endoscopy Biopsy Culture of esophagus swab Upper GI series Barrium solution X-ray of esophagus NB2244 barium coats esophagus lining white on x-ray view abnormalities of esophagus 10  …..Esophagitis PATHOLOGICAL CHANGES Concentric mucosal ring NB2244 Infection 11  …..Esophagitis HISTOLOGICAL CHANGES NB2244 Eosinophilic esophagitis - infiltration of eosinophil Reflux esophagitis - basal cell hyperplasia - Papilla extended almost to surface of mucosa 12  Barret Esophagus Barrett esophagus is a complication of chronic GERD that is characterized by intestinal tissue &metaplasia within the esophageal squamous mucosa abnormal change (replace squamous epithelial by columnar epithelial intestinal metaplasia). NB2244 The presence of the tan tongues of epithelium interdigitating with Transition between esophageal squamous mucosa (lower right) and metaplastic mucosa containing goblet cells (upper). the more proximal squamous epithelium is typical of Barrett esophagus 13 CANCER OF THE ESOPHAGUS Esophagus cancer begins in cells in the inner layer of esophagus Over time invading deeply into the wall of esophagus and surrounding tissue cell (sc] (upper carcinoma squamous 2 types: ~ adenocarcinoma (I ower) ~ Squamous cell carcinoma (SCC) – upper part (more common) Adenocarcinoma – lower part (on rise) NB2244 SCC occurs equally as often in the middle and lower esophagus Risk Factors : male, over 65 yo, smoking,- alcohol, low fibre diet, obesity, acid reflux (Barrett esophagus) # - 14  …..Esophagus Cancer CLINICAL SYMPTOMS ~ susahtelar Dysphagia ~ sakit telan Pain when swallowing (odynophagia) - Pain in the chest or back Weight loss Heartburn NB2244 suara serak Hoarseness, constant cough that doesn’t go away within 2 weeks - - Bleeding into esophagus 15  …..Esophagus Cancer PATHOGENESIS OF SCC SCC is the most common type of esophageal cancer worldwide Major risk factors : tobacco and alcohol in combination lead to increased risk of esophageal cancer Alcohol (solvent, fat soluble) damage the cellular DNA by decreasing metabolic activity within the cell  reduce detoxification function while promoting oxidation The hazardous carcinogens within tobacco are able to penetrate the esophageal NB2244 epithelium easier Carcinogens in tobacco -- aromatic amines, nitrosamines, polycyclic aromatic hydrocarbons, aldehydes Inflammation of the squamous epithelium that leads to dysplasia and in situ malignant change 16  …..Esophagus Cancer PATHOGENESIS OF ADENO-CA Adenocarcinoma of the esophagus occurs in the distal esophagus --- link to gastroesophageal reflux disease (GERD) Untreated GERD can progress to Barrett’s esophagus (BE) Chronic reflux of gastric acid and bile at the gastroesophageal junction and subsequent damage to the esophagus --- pathogenesis of Barrett metaplasia The stratified squamous epithelium that normally lines the esophagus is replaced by a NB2244 columnar epithelium --- esophageal metaplasia The risk of developing esophageal cancer is 50-100 times more likely in those with BE The longer the segment of esophagus affected the higher the risk of adenocarcinoma 17  …..Esophagus Cancer PATHOLOGICAL CHANGES Gastroesophageal Reflux Metaplasia Low Grade NB2244 Dysplasia High Grade Dysplasia Adenocarcinoma 18  …..Esophagus Cancer PATHOLOGICAL CHANGES NB2244 19  …..Esophagus Cancer STAGES OF ESOPHAGEAL CANCER Stages Description of cancer cells 0 Abnormal cells are found only in the inner layer of the esophagus. Carcinoma in situ. I The cancer has grown through the inner layer to the submucosa. II The cancer has grown through the inner layer to the submucosa, and cancer cells have spread to lymph nodes. Or, the cancer has invaded the muscle layer. Cancer cells may be found in lymph nodes. Or, the cancer has grown through the outer layer of the NB2244 esophagus. III The cancer has grown through the outer layer, and cancer cells have spread to lymph nodes. Or, the cancer has invaded nearby structures, such as the airways. Cancer cells may have spread to lymph nodes. IV Cancer cells have spread to distant organs, such as the livers 20  …..Esophagus Cancer PATHOLOGICAL CHANGES NB2244 Features used to stage esophageal carcinoma according to the latest version of the TNM classification system. Notable updates are the classification of T4 lesions as resectable (T4a) or unresectable (T4b), and the stratification of N status on the basis of number of nodes involved. Tis=intraepithelial neoplasia. HGD=high-grade dysplasia. 21  …..Esophagus Cancer PATHOLOGICAL CHANGES NB2244 Esophageal cancer 22  …..Esophagus Cancer LAB DIAGNOSIS Barium swallow upper GI and X-ray Endoscopy Biopsy Staging test – MRI, CT scan, endoscopic ultrasound, bone scan, NB2244 PET scan Laproscopy – small incision in abdomen 23 Overview : Disease of Stomach Congenital Disorders Gastric Polyps and Tumors Congenital Pyloric Stenosis Gastric Polyps Gastritis Gastric Adenocarcinoma Acute Gastritis Carcinoid Tumors Chronic Gastritis Gastrointestinal Stromal Tumors NB2244 Peptic Ulcer Disease 24 INFLAMMATION OF THE STOMACH : GASTRITIS columnar epithelial - cell Inflammation or swelling of stomach lining - Acute gastritis mucosal inflammatory process not permanent transient nature Chronic gastritis NB2244 chronic gastric lesion pathologically characterized by nonspecific chronic gastric mucosal inflammation 25  …..Gastritis TYPES OF GASTRITIS NB2244 26  …..Gastritis ACUTE GASTRITIS 4 Types of acute gastritis: (SHEE) Erosive gastritis nak is j - an ulcer that has not penetrated the muscularis mucosae bleeding Hemorrhagic gastritis inflammation from bacteria - Suppurative (phlegmonous) gastritis adapus NB2244 -- bacterial cellulitis, predominantly affecting submucosal layer Emphysematous gastritis air says - -gas-forming organisms producing submucosal bubbles - - colomite stomach 27  …..Gastritis ETIOLOGY OF ACUTE GASTRITIS ~ erusive NSAIDS eg. aspirin evosive Alcohol consumption - Smoking Systemic infection Gastric irradiation, ischemia NB2244 Shock Stress (eg. burn, trauma, emotional) Following surgery (eg. distal gastrectomy) 28  …..Gastritis PATHOGENESIS OF ACUTE GASTRITIS Mechanism of action: AHB E Increased gastric acid production = Decreased production of surface HCO3 -buffer = Reduced mucosal blood flow causing disruption to mucous layer NB2244 = Damage to mucosal epithelium => 29  …..Gastritis CHRONIC GASTRITIS Types of chronic gastritis: H.pylori-associated gastritis Infectious granulomatous gastritis Cytomegalovirus infection gastritis Autoimmune gastritis Chronic reactive chemical gastropathy NB2244 Chronic noninfectious granulomatous gastritis Lymphocytic gastritis Eosinophilic gastritis Radiation and ischemic-related gastritis 30  …..Gastritis ETIOLOGY OF CHRONIC GASTRITIS Helicobacter pylori Bile reflux NSAIDS eg. naproxen, ibuprofen Autoimmune disorder eg. pernicious anemia Allergic response NB2244 Prolonged chemotherapy Alcohol abuse 31  …..Gastritis PATHOGENESIS OF CHRONIC GASTRITIS Mechanism of action: Injury of gastric mucosa by reflux of bile and pancreatic secretions into stomach Epithelial damage, erosions and ulcer followed by regenerative hyperplasia NB2244 Damage to capillaries with mucosal edema, hemorrhage Increased smooth muscle in the lamina propria 32  …..Gastritis CLINICAL SYMPTOMS Upper abdominal pain – epigastric region Nausea and vomiting Loss of appetite Black stool – melena (upper gastrointestinal bleeding) NB2244 33  …..Gastritis LAB DIAGNOSIS Endoscopy of the upper GI Biopsy Complete blood count H.pylori test NB2244 Barrium swallow & X-ray 34  …..Gastritis PATHOLOGICAL CHANGES NB2244 Acute gastritis – mild mucosal injury Chronic gastritis – pale decolorization Bile reflux gastritis – mucosal injury of the mucosa due to bile reflux - - ① 35 PEPTIC ULCER DISEASE An ulcer where stomach lining is damaged exposing underlying tissue Caused by stomach acid Also called stomach ulcer or gastric ulcer Most common is duodenal ulcer NB2244 36  …..Peptic Ulcer ETIOLOGY Infection of bacteria, commonly H.pylori Regular use of NSAIDS Smoking cigarettes and chewing tobacco Being very ill – low immune system Radiation treatments NB2244 Rare cases caused by Zollinger-Ellison syndrome (tumor in pancreas) 37  …..Peptic Ulcer PATHOGENESIS NB2244 38  …..Peptic Ulcer CLINICAL SYMPTOMS Pain in the upper abdomen below sternum Pain or discomfort wakes you up at night Chest pain Feeling sick or nausea Vomiting, possibly bloody NB2244 Bloody stools Fatigue Weight loss 39  …..Peptic Ulcer PATHOLOGICAL CHANGES = NB2244 40  …..Peptic Ulcer LAB DIAGNOSIS Esophagogastroduodenoscopy (EGD) (upper endoscopy) Culture to detect H.pylori Biopsies around ulcers Barium solution swallowing and X-ray NB2244 41 CANCER OF THE STOMACH : GASTRIC CANCER Gastric cancer can arise from any part of the stomach Genetic predisposition Causes about 800,000 deaths worldwide per year Most common in men after age 50 NB2244 Higher cases in Japan, decreasing in US 42  …..Gastric Cancer ETIOLOGY & RISK FACTORS Mostly caused by H. pylori infections Increased risk levels by Autoimmune atrophic gastritis Intestinal metaplasia Various genetic factors NB2244 Diet – smoked/salted food, pickled Tobacco smoking 43  …..Gastric Cancer CLINICAL SYMPTOMS Asymptomatic or nonspecific symptoms in early stages Often symptoms appear in advanced cancer 3 stages of Signs and Symptoms Stage 1 – indigestion, loss of appetite, abdominal discomfort or irritation Stage 2 – weakness and fatigue, bloating Stage 3 – abdominal pain in upper abdomen NB2244 – nausea and occasionally vomiting – diarrhea and constipation – weight loss – black stools and bloody vomit– dysphagia (difficult swallowing) 44  …..Gastric Cancer LAB DIAGNOSIS Barium swallow upper GI and x-ray Gastroscopic Computed tomography or CT scan Biopsy NB2244 45  …..Gastric Cancer PATHOGENESIS Gastric cancer (GC) is one of the most common cancers in the world, particularly in developing countries Environmental factors play a major role in the carcinogenesis most common diet and infection with Helicobacter pylori Often not detected until an advanced stage --- the 5-year survival rate is low GC is a complex, multistep process involving deregulation of oncogenic signaling pathways --- genetic and epigenetic alterations NB2244 gene mutations, gene amplification, deletions or allelic loss and chromosomal translocations Cause gain-of-function in oncogenes and loss-of-function in tumor suppressor genes --- gastric carcinogenesis 46  …..Gastric Cancer STAGES OF GASTRIC CANCER Stages Description of cancer cells 0 Limited to the inner lining of the stomach. Treatable by endoscopic mucosal resection when found very early (in routine screenings) I Penetration to the second or third layers of the stomach (Stage 1A) Or, to the second layer and nearby lymph nodes (Stage 1B) II Penetration to the second layer and more distant lymph nodes, or the third layer and only nearby lymph nodes, or all four layers but not the lymph nodes. Treated as for Stage I NB2244 III Penetration to the third layer and more distant lymph nodes, or penetration to the fourth layer and either nearby tissues or nearby or more distant lymph nodes. Treated as for Stage II; a cure is still possible in some cases. IV Cancer has spread to nearby tissues and more distant lymph nodes, or has metastatized to other organs. A cure is very rarely possible at this stage. 47  …..Gastric Cancer PATHOLOGICAL CHANGES NB2244 Gastric signet ring cell carcinoma Adenocarcinoma of the stomach Tumor cells secrete mucous, delivered in the interstitium producing large pools of mucous (empty spaces) (arrow) 48 CONGENITAL DISORDER OF THE STOMACH : CONGENITAL PYLORIC STENOSIS *Make simple notes on this topic. NB2244 49 Overview : Disease of Intestinal System The Large Intestine Congenital Disorder Inflammatory Bowel Disease Crohn’s Disease Ulcerative Colitis Vascular Diseases Ischemic Bowel Disease NB2244 Hemorrhoids Colonic Polyps Colon Cancer 50 INFLAMMATION OF THE INTESTINAL SYSTEM : CROHN’S DISEASE unknown An idiopathic, chronic, transmural inflammatory process of the bowel Often leads to fibrosis and obstructive symptoms Can affect any part of GIT; commonly large intestine NB2244 Results of an imbalance proinflammatory and anti- inflammatory mediators 51  …..Crohn’s Disease ETIOLOGY Unknown causes Inheritable Microbial infections Dietary Oral contraceptive pills and NSAIDS NB2244 52  …..Crohn’s Disease CLINICAL SYMPTOMS Low-grade fever Prolonged diarrhea with abdominal pain Weight loss Fatigue Crampy or steady pain of right lower quadrant NB2244 Diarrhea and vomiting Intestinal obstruction 53  …..Crohn’s Disease LAB DIAGNOSIS Barium enema for colon and CT colography Colonoscopy or sigmoidoscopy Cobblestone changes in terminal ileum NB2244 54  …..Crohn’s Disease PATHOLOGICAL CHANGES NB2244 Cobblestone changes in terminal ileum of Crohn’s disease 55  …..Crohn’s Disease HISTOLOGICAL CHANGES NB2244 Crohn’s disease of colon non-caseating granuloma in the lamina propia (arrow) Crohn’s disease of colon Deep fissure extending into muscle wall abundant lymphocytes aggregate (blue) 56 INFLAMMATION OF THE COLON : ULCERATIVE COLITIS Chronic inflammation of large intestine One of diseases called inflammatory bowel disease Ulcers form after inflammation has killed cells lining the rectum and colon NB2244 Closely related to Crohn’s disease, inflammation of intestines country Increased frequency in developing nations - 57  …..Ulcerative Colitis CLASSIFICATIONS Classified according to location and extent of inflammation Ulcerative proctitis – inflammation limited to rectum (a) Proctosigmoiditis – inflammation of rectum and the sigmoid colon (b) Left-sided colitis – inflammation that starts at rectum and extends up the left colon (c) Pancolitis / Universal colitis – inflammation affecting the entire colon (d) NB2244 Fulminant colitis – a rare but severe form of pancolitis 58 …..Ulcerative Colitis NB2244 59  …..Ulcerative Colitis ETIOLOGY Unknown causes Involves abnormal activation of the immune system in the intestines In patients with UC, immune system is abnormally and chronically activated without any triggers NB2244 Genetically inherited 60  …..Ulcerative Colitis CLINICAL SYMPTOMS Rectal bleeding  Anemia Loss of body fluids and nutrients Fatigue Weight loss  Loss of appetite Skin lesions NB2244 Growth failure – specifically in children 61  …..Ulcerative Colitis LAB DIAGNOSIS Stool specimen analysis to exclude infections and parasites Blood tests – may show anemia, elevated WBC Sigmoidoscopy and colonoscopy to visualize the colon Barium enema x-ray NB2244 62  …..Ulcerative Colitis PATHOLOGICAL CHANGES NB2244 63  CANCER OF THE COLON : COLON CANCER Commonly colorectal cancer or bowel cancer Uncontrolled cell growth in colon or rectum Starts in lining of the bowel, if untreated can grow into muscle layers underneath, and through the bowel wall. NB2244 64  …..Colon Cancer RISK FACTORS Geografic variation : Common in US/Europe vs Asia/Africa Older than 60 of age (increased incidence in younger age) Dietary factors : Low dietary fiber intake High animal fat (red meat/processed meat) intake High refined carbohydrate intake Deficiency of Vit A/C/E NB2244 Obesity, lack of exercise, smoking, alcohol Family history of colon cancer : first degree relative People with ulcerative colitis and Crohn’s disease, history of polyps/colorectal cancer. 65  …..Colon Cancer Pathogenesis Most colorectal cancers develop from the combination of multiple molecular alterations. The molecular events include : Genetic abnormalities (that activate oncogenes or inactivate tumor suppressor genes) Epigenetic abnormalities. Creversible) Genetic pathways : NB2244 Adenoma-carcinoma Sequence (APC/-catenin Pathway) mutations lead to increased WNT signaling Microsatellite Instability Pathway are associated with defects in DNA mismatch repair 66  …..Colon Cancer Pathogenesis APC/-catenin Pathway NB2244 1. Inactivation of APC tumor suppressor gene : accumulation of -catenin  promotes cell proliferation. 2. K-RAS mutations: Loss of APC function is followed by mutations in proto-oncogene K-RAS, which results in oncogene K-RAS  promotes cell proliferation and also prevents apoptosis. 3. SMAD2 and SMAD4 (tumor suppressor gene) mutations: lead to uncontrolled cell proliferation 4. Activation of telomerase: Telomere plays a role in stabilizing the chromosome. 67 APC - adenomatous polyposis coli  …..Colon Cancer Pathogenesis Microsatellite Instability Pathway NB2244 Defects in mismatch repair genes result in microsatellite instability and allow accumulation of mutations in numerous genes involved in cell survival and proliferation 68  …..Colon Cancer CLINICAL SYMPTOMS Depends on location of tumor in the bowel Right-sided (20%) area : asymptomatic, weight lost, iron deficiency, palpable mass Descending sigmoid (75%) area : bloody stool, abdominal pain, increase bowel frequency, bloating & flatulence, mucous present. Rectal area : abdominal pain with/without tenesmus, bloody stool, sensation of incomplete evacuation (growth tissue) Worsening constipation NB2244 Loss of appetite  Unintended weight loss Nausea and vomiting Rectal bleeding  blood in stool  anemia 69  …..Colon Cancer LAB DIAGNOSIS Depends on colonoscopy – to view entire colon and rectum for abnormalities Biopsy – through colonoscopy, small tissue samples cut for analysis of cancer markers (staging of cancer) CT scan – images to create a detailed picture of the cancer inside of colon and rectum (staging of cancer) NB2244 Blood test – complete blood count, organ-function tests Barium enema – to evaluate the entire colon with an X-ray of tumor in the bowel 70  …..Colon Cancer STAGES OF COLON CANCER Stages Description of cancer cells 0 Abnormal cells only limited to the inner lining of the colon/rectum wall. I Cancer cell have grown through the superficial lining (mucosa) of the colon or rectum but has not spread beyond the colon/rectum wall. II Cancer cells have grown into or through the wall of the colon/ rectum but has not spread to nearby lymph nodes. III Cancer cells invaded nearby lymph nodes but is not affecting other NB2244 parts of the body yet. IV Cancer cells have spread to distant sites, such as other organs — for instance to the liver or lung. 71  …..Colon Cancer STAGES OF COLON CANCER NB2244 72  …..Colon Cancer PATHOLOGICAL CHANGES NB2244 Invasive colorectal carcinoma -appearance inside of colon Endoscopic image of colon cancer in sigmoid colon 73 DISEASES OF THE APPENDIX : APPENDICITIS https://www.youtube.com/watch?v=r9amif1DQMc NB2244 74