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1、ULCERATIVE COLITISDEFINITIONnUlcerative colitis is a chronic disease characterized by inflammation of the mucosa and submucosa of the large intestine.nThe main clinical manifestations include diarrhea,abdominal pain.nThe incidence and prevalence of the disease vary greatly with geographic location.E
2、PIDEMIOLOGYn Rates are highest in northern climates and in well developed areas of the worldn Bimodal age distribution 15-40 and 50-80n Males Femalesn Tends to run in familiesnGenetic factors Approximately 10%20%of patients with ulcerative colitis have first-degree relatives who also have the same d
3、isease.CD:NOD2/CARD15 gene mutation NF-kB ETIOLOGYnImmunological factors Clear evidence exists for the activation of the immune response in ulcerative colitis.Three major hypothesis as to the antigenic triggers in ulcerative colitis have been postulated.Microbial pathogens Dietary antigen or usually
4、 nonpathogenic microbial agent autoimmune theory:One antibody against a 40-KD protein that has been identified as tropomysin.nInflammation Neutrophils,lymphocytes,mast cells,NK Inflammatory cytokines:IL,TNF,IFN-r leukotriene B4(LTB4)superoxide and other reactive oxygen species(ROS)PATHOLOGYnUlcerati
5、ve colitis involves primarily the mucosa of the colon.The inflammation usually begins in the rectum,and may extend proximally in the colon for variable distance.nMacroscopic features of pathologic specimens in ulcerative colitis depend on the severity and duration of the disease.PATHOLOGYnIn chronic
6、 disease,the mucosa loses its normal folds and becomes flat.Inflammatory polyps or pseudopolyps may be present.nIn quiescent ulcerative colitis,the inflammation is less intense than in active disease.The number of crypts is reduced and often branched.CLINICAL FEATURESnSymptoms and signs Diarrhea Abd
7、ominal pain Others:anorexia,nausea,vomiting Signs:generalized tenderness localized tenderness,with“rebound”bowel soundCLINICAL FEATURESnSystemic manifestations Fever Fatigue Weight loss Anemia HypoproteinemiaCLINICAL FEATURESnClinical types Initial attack Chronic relapse Chronic continuance Acute fu
8、lminatenThe degree of severity Mild Moderate SevereMild DiseasenIntermittent rectal bleeding with mucusn Mild diarrhea(4 small stools/day)n Mild crampy abdominal painn Tenesmus and periods of constipationModerate DiseasenFrequent loose,bloody stools (6/day)n Mild anemia not requiring transfusionsn A
9、bdominal pain that is not severen Low grade fevern Usually able to maintain adequate nutritionCOMLICATIONnToxic megacolonnCarcinoma of the rectum and colonnOthers:massive bleeding,perforation,strictureCOMPLICATIONLABORATORY FINDINGSnColonscopy Loss of the fine vascular pattern A geanular appearance
10、Superfical ulcerations Mucopus Postinflammatory polypsCOLONSCOPYCOLONSCOPYCOLONSCOPYCOLONSCOPYCOLONSCOPYLABORATORY FINDINGSnRadiography Collar-button ulcers Nodular/filiform Granularity of mucosa Disappear of the hastral markings RADIOGRAPHYRADIOGRAPHYDIAGNOSISnThe diagnosis of ulcerative colitis is
11、 based on clinical features,laboratory tests,and endoscopic and histologic features.How UC is DiagnosednClinical historynPhysical examinationnLab testsnEndoscopy(Colonoscopy)nX-raynTissue biopsy(Pathology)DIFFERENTIAL DIAGNOSISnInfectious colitisnCrohns diseasenColon cancernIrritable bowel syndromen
12、Ischemic colitisnRadiation colitisnDiverticulitisDIFFERENTIAL DIAGNOSIS ulcerative colitis Crohns diseaseSite Rectum always Any segment of the colon only gastrointestinal tractPattern Continuous SkipDiarrhea Bloody Usually nonbloodyFistula No YesEndoscopic Erythema,friable,Aphthoid ulcers,deepfindin
13、gs superficial ulcerations ulcersHistologic Crypt abscess Granulomas(30%)features TREATMENTnGeneral therapy Nutrition Antidiarrheal medications AntibioticsnDrug therapy Sulfalazine(SASP)5-aminosalicylic(5-ASA)Corticosteroids Immunosuppressive agentsTREATMENTnSurgical treatment Emergent operation Sel
14、ective operationnFuture therapy5-ASAnInduce remissions in mild-moderate UCnMaintain remissions in mild-moderate UCnMaintain remissions in CD after medical treatment Surgical resections5-ASABenefits RisksWell-tolerated Rare allergies/Few side effects side effectsRelatively inexpensive Not helpful in
15、severe diseaseOral or Rectal Not helpfulSafe for all ages&after steroidspregnancyCorticosteroidsnPrednisone,Hydrocortisone,Budesonide,Medrol,Decadron,Cortenema,Cortifoam,ACTHnAdministered by pill,IV or enemanInduce remissions in UCnNo maintenance denefitsCortcosteroidsBenefits RisksInduces remission
16、s No long-term benefitsQuick fix Numerous side effects Inexpensive Cushingoid changes Oral or rectal Hypertension Diabetes Osteoporosis Growth retardationAntibioticsnFlagyl(Metronidazole),Ciprofloxacin,Ampicillin,etc.nIntravenous to treat severe colitis or infections such as abscessAntibioticsBenefi
17、ts Risks Mild-moderate CD Not effective in UC Fistula and peri-anal CD Flagyl Reduce recurrence Neuropathy After surgery(?)Coated tongue Yeast infections Ciprofloxacin Yeast infections Tendon injuryImmune-ModulatorsnLong-term(maintenance)treatments nPrimarily for patients unable to get off Steroidsn
18、Requires continuous monitoring of blood testsImmune-Modulators Imuran&6-MP Benefits RisksSteroid-sparing Can lower blood counts and immunity Long-term Requires long-term Maintenance monitoring Relatively Occaional allergies Inexpensive fever,pancreatitisCyclosporine Benefits RisksEffective in severe
19、 UC Kidney damageEffective in CD?Incresed infectionsWorks rapidly Seizures Hypertension Tumors?UC:Indicatios for SurgerynFailure to control severe attacks or toxic megacolonnAcute complicationsnChronic symptoms despite medical therapynMedication side effects without disease controlnDysplasia or Canc
20、erPROGNOSISnGood for the patients with mild form of ulcerative colitis and long-term remission.Poor for the patients with replase of the acute attack.Worse for the patients with fulminant ulcerative colitis,the presence of complications and more than 60 ages.Colorectal Cancer Risks nCompared to gene
21、ral population -Risk is 20 times higher and -Occurs at lower agenRisk is same for UC according to:-How much of colon is affected How long the disease is present If patient has liver disease(PSC)nRisk may be related to severity/activity of diseasePreventing Colon CancernCompliance with maintenance medicatiions -5-ASA agentsnRegular follow-up and surveillance colonscopiesnColectomy(removal of colon)if:Dysplasia THANK YOU
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