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AcutePancreatitisRajeevJain,M.D.December15,2003NormalAnatomy&Physiology•neutralizechyme•digestiveenzymes•hormonesExocrineFunctionpancreaticductcommonbileductampullapancreaticenzymesTAILBODYHEADUNCINATEEnzymeSecretionpancreaticductduodenumacinusmicroscopicviewofpancreaticaciniEnzymeSecretionHormonalCCKgastrinNeuralacetylcholineVIPGRPSecretin(hormonal)H2ObicarbonateDigestiveEnzymesinthePancreaticAcinarCellPROTEOLYTICLIPOLYTICENZYMESENZYMESLipaseTrypsinogenProphospholipaseA2ChymotrypsinogenCarboxylesteraselipaseProelastaseProcarboxypeptidaseANUCLEASESProcarboxypeptidaseBDeoxyribonuclease(DNAse)Ribonuclease(RNAse)AMYOLYTICENZYMESAmylaseOTHERSProcolipaseTrypsininhibitorNormalEnzymeActivationtrypsinogentrypsinchymotrypsinelastasephospholipasecarboxypeptidaseenterokinasechymotrypsinogenproelastaseprophospholipaseprocarboxypeptidaseduodenallumenExocrineStimulation•Themoreproximalthenutrientinfusion…thegreaterthepancreaticstimulation(dogstudies)-stomach–maximalstimulation-duodenum–intermediatestimulation-jejunum–minimal/negligiblestimulation•Elementalformulastendtocauselessstimulationthanstandardintactformulas-intactproteinoligopeptidesfreeaminoacids•Intravenousnutrients(evenlipids)donotappeartostimulatethepancreasProtectiveMeasures•COMPARTMENTALIZATION-digestiveenzymesarecontainedwithinzymogengranulesinacinarcells•REMOTEACTIVATION-digestiveenzymesaresecretedasinactiveproenzymeswithinthepancreas•PROTEASEINHIBITORS–trypsininhibitorissecretedalongwiththeproenzymestosuppressanyprematureenzymeactivation•AUTO“SHUT-OFF”–trypsindestroystrypsininhighconcentrationsAcutePancreatitisDefinition•Acuteinflammatoryprocessinvolvingthepancreas•Usuallypainfulandself-limited•Isolatedeventorarecurringillness•Pancreaticfunctionandmorphologyreturntonormalafter(orbetween)attacksEtOH35%Idiopathic10%Other10%Gallstones45%AcutePancreatitisEtiology•Cholelithiasis•Ethanolabuse•Idiopathic•Medications•Hyperlipidemia•ERCP•Trauma•Pancreasdivisum•Hereditary•Hypercalcemia•Viralinfections-Mumps-Coxsackievirus•End-stagerenalfailure•PenetratingpepticulcerAcutePancreatitisAssociatedConditionsAcutePancreatitisCausativeDrugs•AIDStherapy:didanosine,pentamidine•Anti-inflammatory:sulindac,salicylates•Antimicrobials:metronidazole,sulfonamides,tetracycline,nitrofurantoin•Diuretics:furosemide,thiazides•IBD:sulfasalazine,mesalamine•Immunosuppressives:azathioprine,6-mercaptopurine•Neuropsychiatric:valproicacid•Other:calcium,estrogen,tamoxifen,ACE-IAdjustedORsforPancreatitis2.54.812.442.1051015202530354045Pancreatitis,ORsFemaleNlTBiliSODDifficultcannulationFreemanetal.GastrointestEndosc.‘97.PancreasdivisumHereditaryPancreatitis•Autosomaldominantwith80%phenotypicpenetrance•Recurrentacutepancreatitis,chronicpancreatitis,and50-foldincreasedriskofpancreaticcancer•Mutationincationictrypsinogengene(R122H)•Othergeneticdefects-CFTR-SPINK1failedprotectivemechanismsacinarcellinjuryprematureenzymeactivationAcutePancreatitisPathogenesisautodigestionofpancreatictissuereleaseofenzymesintothecirculationactivationofwhitebloodcellslocalcomplicationslocalvascularinsufficiencyprematureenzymeactivationdistantorganfailureAcutePancreatitisPathogenesis•STAGE1:PancreaticInjury-Edema-Inflammation•STAGE2:LocalEffects-Retroperitonealedema-Ileus•STAGE3:SystemicComplications-Hypotension/shock-Metabolicdisturbances-Sepsis/organfailureSEVERITYMildSevereAcutePancreatitisPathogenesis•Abdominalpain-Epigastric-Radiatestotheback-Worseinsupineposition•Nauseaandvomiting•FeverAcutePancreatitisClinicalPresentationAcutePancreatitisDifferentialDiagnosis•Choledocholithiasis•Perforatedulcer•Mesentericischemia•Intestinalobstruction•Ectopicpregnancy•Symptoms-Abdominalpain•Laboratory-Elevatedamylaseorlipase•3xupperlimitsofnormal•Radiology-AbnormalsonogramorCTAcutePancreatitisDiagnosisCausesofIncreasedPancreaticEnzymesAmylaseLipasePancreatitis↑↑Parotitis↑NormalBiliarystone↑↑Intestinalinjury↑↑Tubo-ovariandisease↑NormalRenalfailure↑↑Macroamylasemia↑NormalAcutePancreatitisDiagnosis•EtOH:history•Gallstones:abnormalLFTs&sonographicevidenceofcholelithiasis•Hyperlipidemia:lipemicserum,Tri1,000•Hypercalcemia:elevatedCa•Trauma:history•Medications:history,temporalassociationAcutePancreatitisClinicalManifestationsPANCREATICPERIPANCREATICSYSTEMICMild:edema,inflammation,fatnecrosisSevere:phlegmon,necrosis,hemorrhage,infection,abscess,fluidcollectionsRetroperitoneum,perirenalspaces,mesocolon,omentum,andmediastinumAdjacentviscera:ileus,obstruction,perforationCardiovascular:hypotensionPulmonary:pleuraleffusions,ARDSRenal:acutetubularnecrosisHematologic:disseminatedintravascularcoag.Metabolic:hypocalcemia,hyperglycemiaAcutePancreatitisTimeCourse01224364860728496hoursfrompainonsetERpresentationcytokinereleaseorganfailurePredictorsofSeverity•Whyaretheyneeded?-appropriatepatienttriage&therapy-compareresultsofstudiesoftheimpactoftherapy•Whenaretheyneeded?-optimally,withinfirst24hours(damagecontrolmustbeginearly)•Whichisbest?SeverityScoringSystems•RansonandGlasgowCriteria(1974)-basedonclinical&laboratoryparameters-scoredinfirst24