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Gastrointestinal PathologyDan Lodge-Rigal, MDReading: Big Robbins, Chapter 17, plus Chapter 16 pp 758-762 Wheater: Alimentary chapter Online exercise: Mr. Jones’ Nausea, case 5 on the website and CD. Lab test: CEA, stool for occult blood, H. pylori antibodies, Celiac disease antibodies.Slides: 9, 19, 20, 21, 32, 59, 98, 104, 131, 138, 143, 144, 173, 183, 194, 199, 212, 216, 222Reading: Robbins Basic Pathology 9th edition, Chapter 14 (pp. 551-602)OUTLINEOral Cavityaphthous ulcersinfectionsbenign tumorsleukoplakia and squamous epithelial abnormalitiessquamous cell carcinomaSalivary Glandinflammation and infectionnon neoplastic “tumors”neoplasms: benignneoplasms: malignantEsophaguscongenital: esophageal atresiafunctional disorders: diverticula, webs and rings, achalasia, hiatal herniagastroesophageal varicesinflammation (esophagitis)gastroesophageal reflux disease (GERD) and Barrett esophaguseosinophilic esophagitistumors: benigntumors: malignantStomachcongenital: pyloric stenosisgastritis: mechanismsacute and chronic gastritispeptic ulcer diseasegastric polypsgastric cancerother neoplasms of the stomachLarge and Small Intestinecongenital: Hirschprung diseasediarrheal disease: classificationceliac diseasemicroscopic colitisinfectious gastroenteritis: viralinfectious enterocolitis: bacterialinfectious enterocolitis: parasiticlab testing for diarrheal diseasesinflammatory bowel diseasediverticular diseaseischemic bowel diseasepolyps: non-neoplasticpolyps: adenomascolon cancer (adenocarcinoma)anal cancerNon-epithelial tumors of the GI tractcarcinoidlymphomaAppendixGastrointestinal PathologyDan Lodge-Rigal, MDOral CavityAphthous ulcersInfection:Herpes simplexCandida (thrush)Tumors:427482015875000Benign:FibromaPyogenic granulomaChanges of the squamous epithelium:Hyperplasia (pseudoepitheliomatous hyperplasia)Leukoplakia and Erythroplakia (clinical diagnosis: white patch)Malignant:42748204508500Cancer of the oral cavity (squamous cell carcinoma)Causative factors:1)2)3)Natural history of squamous cell cancers of the oral cavitySalivary GlandsNormal salivary gland structure and functionInflammation of the salivary glands: sialadenitisInfections:1)2)3)40462205334000AutoimmuneNon-neoplastic "tumors":Mucocele and ranulaNeoplasms:General concepts:Size of gland versus risk of malignancyBenign tumorsBenign mixed tumor (pleomorphic adenoma)313182011620500Warthin tumor (adenolymphoma)Malignant tumorsMucoepidermoid carcinomaAdenoid cystic carcinoma LymphomasMetastatic tumorsEsophagusNormal Esophagus:Layers:1)2)3)4)G-E JunctionZ-lineLower esophageal sphincterLower esophageal sphincterlocation:427482016129000regulation of LES tone:Signs and symptoms of esophageal disease:1)2)3)4)Congenital disorders of the esophagus: Atresia and tracheo-esophageal fistula416052011620500Functional (motor) disorders of the esophagus:DiverticulaStenosisEsophageal webs and Schatzki ringAchalasiaprimary versus secondarycancer risk3036570-3365500Hiatal HerniaEsophageal hemorrhageGastro-esophageal varicesPathogenesis:Natural history and treatmentInflammatory disorders of the esophagus (Esophagitis)Non-infectious 1)2)3)Infectious:1)2)Gastroesophageal reflux disease (GERD)Incidence:Causative factors for GERD:1)2)3)4)36417259969500Effects of gastric acid on esophageal mucosa:1)2)Symptoms versus Pathologic changesStrictureBarrett EsophagusDefinition:357822515303500Significance of Barrett esophagus:DysplasiaAdenocarcinomaNatural history and management of Barrett esophagus:Eosinophilic esophagitisTumors of the EsophagusBenign tumors (rare)PapillomaLeiomyomaMalignant tumorsCarcinomas most common.Signs and symptoms of esophageal cancer:1)2)3)4)AdenocarcinomaIncidence:Risk factors:1)2)3)Pathologic findings:Location and gross appearance:Histopathology:Squamous cell carcinomaIncidence:Risk factors:1)2)3)Pathologic findingsLocation and gross appearance:Histopathology:Natural history and treatment of esophageal cancerStaging of esophageal cancers:-8382013081000 diseasemanagement/hematology-StomachAnatomy and histology of the stomach:Regions:297180040640001)2)3)4)Surface epithelium:Gastric glands, cell types1)2) Robbins 6th ed,3)4)Phases of digestion:1)2)3)Factors controlling gastric acid secretion:1)2)3)Factors maintaining gastric mucosal integrity:1)2)3)4)5)Congenital disorder of the stomach:Pyloric stenosisAdults: acquired pyloric stenosisGastritis (acute and chronic) Mechanisms of acute mucosal injury:1143004572000Acute GastritisCommon causes of acute gastritis:1) NSAIDS Mechanism:2)3)4) 5)Pathology:Clinical course:Acute peptic ulceration:Stress ulcersCurling ulcersCushing ulcersChronic GastritisChronic Gastritis associated with Helicobacter PyloriAcquisition and incidence of H. pylori infectionPathogenesis of H. pylori infectionFeatures of H. pylori1)2)3)4)Pathology of H.pylori associated gastritisActive chronic gastritisanatomic distribution of injuryhistopathologyPeptic ulcer diseaseIntestinal metaplasia and dysplasiaComplications of H. pylori infection:Neoplasms:1)2)Diagnosis of H. pylori infection:Antibody testsAntigen testsBiopsyUrea Breath tests (UBT)TreatmentChronic Gastritis associated with Autoimmune disease (pernicious anemia) Less common (10%)Pathogenesis:Antibodies:1)2)Pathologic featuresanatomic distribution of injury"atrophic gastritis"Intestinal metaplasia and dysplasiaPeptic Ulcer DiseaseIncidenceMajor causes of PUD:1)2)44380159715500Other:Pathogenesis of PUD:Relationship of Chronic gastritis to Peptic ulcer diseaseOther associated conditions:Pathologic features:Complications of peptic ulcers:Neoplasms of the StomachPolyps:Hyperplastic polyps and Fundic gland polypsAdenomasGastric CancerIncidence and EpidemiologyHi incidence areas:Recent trendsPathogenesis:Associated factors:Genetics:Infections: H pyloriOther: Pathology:Early vs Advanced35540956604000Intestinal type:Diffuse type: Linitis plastica (leather bottle stomach)Natural history:Metastasis: Staging and Survival: NeoplasmsCarcinoid (neuroendocrine)LymphomaGastrointestinal stromal tumor (GIST)Diseases of Small and Large IntestineNormal gross and microanatomySmall intestine:VilliCell types1)2)3)4)MALTLarge intestine:CryptsCongenital Disorder: "Congenital Megacolon" Hirschprung DiseaseEtiology:Clinical presentation and natural historyDiarrheal Disease:Definition:Classification of diarrhea:SecretoryOsmoticMalabsorptiveExudativeOther: "motility disorders"Celiac DiseaseDefinition and EpidemiologyClinical presentation17145009144000PathogenesisPathologic findings:1)2)3)Diagnosis of Celiac DiseaseAntibody tests:Molecular tests: Treatment Microscopic colitis:Collagenous colitisLymphocytic colitisInfectious EnterocolitisViral gastroenteritisRotavirusNorovirusBacterial EnterocolitisClinical Scenarios:Acute watery diarrheaDysenteryShigella, Campylobacter, non-typhoid salmonella, Shiga-toxin producing E coliFood PoisoningStaph aureus, Clostridium perfringens, Bacillus ceruesTraveler's DiarrheaE coliOther: shigella, salmonella, campylobacter, aeromonas species, non-cholera vibriosNosocomial diarrheaClostridium difficileSpecific Pathogens:Vibrio cholerae2846705-36830000Campylobacter jejunitoxins and invasionextraintestinal complicationsShigella speciesinvasion and type III secretion systemShiga toxinSalmonella (non--typhoid strains)type III secretion system and invasionSalmonella typhi (typhoid fever)lymphatic and hematogenous dissemination331470014478000E coli (4 types)1)2)3)4)Clostridium difficile and pseudomembranous colitisPathogenesis and incidence:Diagnosis:Toxin testsPCR testsTreatmentEpidemic strain: toxin hyperproducer (NAP-1 strain)Parasitic DiseaseGiardia lambliaEntamoeba histolyticaLaboratory tests for Diarrheal Diseases:Tests for malabsorption:Hydrogen breath testsFecal fatFecal osmolarityTests for inflammationFecal leukocytes and lactoferrinC-reactive proteinTests for infectious agentsDetection of toxins and antigens (rapid) (immunoassay)Detection of DNA (PCR) (rapid)Detection of the microorganisms:Stool cultureOva and ParasitesInflammatory Bowel Disease29718001587500Ulcerative Colitis and Crohn DiseaseEpidemiology and Pathogenesis:Genetics:Mucosal immune responses:Epithelial defects:Microbiology:Pathologic features of Inflammatory Bowel DiseaseCommon features:1)2)3)4)Crohn diseaseIncidence and epidemiologyAnatomic distribution:Distinguishing features:1)2)3)4)Clinical course and complications:33147009906000Ulcerative ColitisIncidence and epidemiologyAnatomic distribution: Distinguishing features:1)2)3)Clinical course and complicationsExtraintestinal manifestations of Inflammatory Bowel Disease1)2)3)4)Diverticular diseaseEpidemiology PathogenesisPathologic featuresComplications:1)2)3)Ischemic bowel diseaseNormal vascular supply to intestine and areas at riskPathogenesis (mechanisms)1)2)3)4) Other:Pathologic features:14859009969500 Robbins 6th ed.Tumors of the Small and Large IntestineDifferences in neoplasms of small versus large intestinePolyps:Non-neoplastic polyps:Hyperplastic polypsSessile serrated polypsHamartomatous polyps:1)2)AdenomasPathologic definition:Types of adenomas:gross appearance:1)2)microscopic appearance:1)2)328739538735003)Adenomas as precursors to cancer epidemiological observationspolyposis syndromesFamilial Adenomatous Polyposis (FAP) and the APC geneHereditary Non-polyposis Colon Cancer (HNPCC)Colon Cancer (Adenocarcinoma)EpidemiologyIncidence:Death from colon cancer:Environmental factors:Molecular carcinogenesis:APC/Beta-catenin pathway013525500Microsatellite instability (MSI) pathway 05080000Pathology of colon cancerDistribution of cancersGross and endoscopic appearance:Microscopic features:Natural history:Local growth:Metastasis:25146009144000Prognosis and Staging:-11430016764000 uploads/2011/04/Colon-Cancer-Staging-And-Survival1.jpgTreatment:Screening for colorectal cancer:Fecal occult blood tests:chemical (guaiac-based)immunochemicalsigmoidoscopy and colonoscopyAnal Cancer:EpidemiologyPathologic featuresNatural historyNon-epithelial neoplasms of the GI tract:Carcinoid (well differentiated endocrine carcinoma)Anatomic distribution and behaviorPathologic featuresClinical features: carcinoid syndromeLymphomasAnatomic distributionB cell lymphomaMALT-omasOther B cell lymphomasT cell lymphoma (rare)associations:AppendixAcute appendicitisTumors of the appendixGASTROINTESTINAL PATHOLOGYSTUDY QUESTIONSOral Cavity:1) What is leukoplakia? What causes it?2) What are some risk factors for cancer of the oral cavity?3) What are 3 types of odontogenic cysts? Which one is likely to be clinically aggressive?Salivary GlandWhat condition(s) predisposes to bacterial sialadenitis?Correlate the clinical features of Sjogren syndrome with the pathologic features.What salivary gland abnormalities are associated with HIV infection? What phase of HIV infection are they found in?What is the most common tumor of salivary glands?What are the most likely tumors to metastasize to salivary gland?Tumors of minor salivary glands are more likely to be ?benign/malignant?EsophagusWhat is Plummer-Vinson syndrome? What are 2 types of hiatal hernia? Which is more common? Complications?What are the 3 pathologic changes seen in reflux esophagitis?Name 3 complications of reflux esophagitis.What factors are associated with gastroesophageal reflux (GERD)?What is Barrett’s esophagus? What is it’s clinical significance?List 5 agents/conditions associated with esophagitisWhat percentage of patients die with their first variceal bleed?What are 6 factors associated with development of esophageal cancer?What histologic type of esophageal cancer is most prevalent worldwide?What factors contribute to the overall poor prognosis of patients with esophageal carcinoma?To where does esophageal cancer spread?What is achalasia? What causes it? What is a potential risk associated with achalasia?StomachWhat are the secretory product(s) of parietal cells?, chief cells?, G cells?, EC-like cells?List 4 factors important in gastric mucosal protection.Projectile vomiting in an infant with a palpable “mass” in the epigastrium is characteristic of what disorder?What is the mechanism underlying NSAID-related gastric mucosal injury?What is the difference between a gastric EROSION and ULCER?Define chronic gastritis.List 6 etiologies of chronic gastritis.What are 4 virulence factors produced by Helicobacter pylori. What is their function?List 4 associated gastric/duodenal disorders associated with H. pylori infection.How does autoimmune gastritis differ from environmental (H-pylori associated) gastritis?What metaplastic change is associated with chronic atrophic gastritis?How does autimmune gastritis cause megaloblastic anemia?Which type of chronic gastritis is associated with hyperplasia of G cells and achlorhydria?What is the most common site of peptic ulceration?Peptic gastric ulcers are most often located on the lesser/greater curvature.Malignant gastric ulcers are most often located on the lesser/greater curvature.What histologic zones can be seen in in a chronic peptic ulcer.What are 3 potential complications of peptic ulcers/Name some conditions associated with acute (stress) gastric ulcerations.Of what clinical significance are thickened gastric folds?What is the mortality rate from gastric carcinoma in the US? Where are high incidence areas for gastric cancer?What histologic type of cancer is most commonly found in the stomach?A “polyp” in the stomach is usually one of 3 possible histologic types. What are they? Which one is most closely associated with pare intestinal versus diffuse types of gastric carcinoma with respect to incidence, underlying gastritis, dysplasia, clinical behavior.What are some etiologic factors associated with gastric carcinoma?What is a Krukenberg tumor?What is linitis plastica?What is “early gastric cancer”? How do early and advanced gastric cancer differ as to prognosis?Small and Large IntestineWhat embryonic remnant gives rise to Meckel’s diverticulum? What significance can heterotopic mucosa have in a Meckel’s diverticulum?What is the cause of Hirschprung disease?Distinguish between secretory, osmotic, exudative, and malabsorptive diarrhea. What lab tests might be useful in making this distinction?What is dysentery?What is the most common viral cause of diarrhea?What are 3 mechanisms by which bacteria cause diarrheal illness?What is pseudomembranous colitis? What are 2 causes of pseudomembranous colitis?What is the organism responsible for Whipple’s disease? What is the treatment?List 6 mechanisms for malabsorption. What are examples of each?What is the significance of a positive anti-tissue transaminase antibody test? How does genetic testing help in the diagnosis of celiac disease?What is the basic pathogenesis of celiac disease?How do Crohn disease and Ulcerative Colitis differ as to: distribution of involved bowel, extent of involvement of bowel wall, type of inflammation, complications, malignancy risk?What segment of colon is most at risk for ischemic injury? What are 4 mechanisms of bowel ischemia?What are 3 complications of diverticular disease?What is intussesception? What segment is most commonly involved in young children?What pathologic features characterized a colonic adenoma (adenomatous polyp)What are Peutz-Jeghers polyps?Describe the difference between a sessile and pedunculated polyp.What features of a polyp are significant with regard to risk of carcinoma?What is the significance of carcinoma arising in a polyp? What criteria must be met for polypectomy to be assumed to be adequate therapy?Describe the genetic abnormality in familial adenomatous polyposis coli (APC) and its significance in colon carcinogenesis. What is other evidence for the “adenoma-carcinoma” sequence?How do carcinomas of the right and left colon differ ?What are sites of spread for colonic carcinoma?What are the important components of the staging system for colon cancer?What is the most common site of carcinoid tumors of the GI tract?What is a MALT-oma?How does carcinoma of the anal canal differ from colorectal cancer (adenocarcinoma)? ................
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