DIGEST TIVEDOMAIN O

Esophagus
ispropria:innercircularmm,outer Musculari longitudin nalmmw/myentericplexu us(Auerbach); Embryology:Fromc cranialforegut,existsbyw wk3 Adventitia a gestation mC6T11/12.~25cminad dult. Anatomy:goesfrom 3Narrowings:cricoiidcartilage,aorticarch,diaphragm Wall: eratinizing Mucosa(smooth,gllistening,pinktan)nonke sepitheliallayer(maturesq quamous stratifiedsquamous servecells),laminapropria a(areolar dcellsoverbasalres CT,vascular,leukocy ytes,haspapillaethatgointo epitheliallayer),mu uscularismucosa(mmw/lo ongitudinal orientation); CTw/vessels/lymphatics,le eukocytes, Submucosa:looseC nerves(gangliaofM Meissnersplexus),glandst thatsecrete mucin; Esophagealphase:movement m alongesophagu us(Problems25secondsa afterswallowing,usuallyas ssociated LowerEsophagealrelaxation/entranceinto w/spasm/carcinoma a) stomac ch:(problemsassociatedw/narrowing w at PrimaryPerist talsis:initiatedbyswallow wingUESopens,foodpus shedinbyperistalticwavethatstartedin lowere endofesophagus).LEShasno pharynx(24cm/sec), c UESthencloses.LESopensandthencloses s.Contractionsdontgoto ogastric anatom micalmarkermadeofsmoothmm musculature highpr ressurezoneof24cmbetweenlower o UES:atlevelofcricopharyngeusmm. m Highpressurezone,c correspondstolowerphary yngealmm esopha agusandstomachresulting gfrom group.24cmlength.Resultsfro omtoniccontractions.Itre elaxesduringswallowingr reflex.Its continu uous/toniccontractionsof circular purpose eistopreventairfroment teringtheesophagus.Dys sfx=zenkersdiverticuli,cric copharyngeal smooth hmm.Preventsgastriccontentsfrom achalasia. moving gfromstomachesophagus.Relaxes SecondaryPeristalsis:initiatedwithoutswallowingoranyCNSinp putpropulsivecontractionsare w/swallowtoallowfoodtoenter rthestomach. stimulatedbyesophagealdistention.Im mportantformovingfooda andrefluxedacidtostoma ach.Enteric (tone bygastrin,Ach,5H,PGF2 2a,motilin, nervessenselower l esophagealdistensio onandsignalinterneurons s(atmyentericganglia)tosignalmotor SubP,Histamine,Pancreaticpoly ypeptide;tone neuronstocauselocalcontraction. byN NO,VIP,Co ee,fats,EtOH, TertiaryPerist talsis:abnormaloftense eenw/age.Nonperistaltic,,spastic,uncoordinatedco ontractions progesterone,chocolate,peppermint,gastric occurindistal lesophagus. pressure) Refluxdysplasia d (intestinaltype)Barrettsadenocarc cinoma

Normal:

Swallowing

Oralpharyngealphase:transfe eroffoodfrommouthesophagus e (Problemsupon n swallowingusuallyfromneur romusculardisease) Bite/chew:Startsbefore eswallowingodor/taste/ /sightgenerateafferent impulsestomedullawhi ichsendsimpulsestosaliva arygland,stomach, pancreas o Salivate:flowisANS A regulated(Achparasym mpatheticinputstimulates +smell,chew,tast te,nausea,conditioning,esophageal e distention; sleep,fatigue,deh hydration,fear),canbeaffectedincompositionby ADHandaldostero one.flowratealsoNa+/bicarb/Cl N content, K+content o Salivaishypotonic c,hashighK+.Containsan ntibacterialagents (lysozyme,lactofe errinIgs,fluoride,Ca++,alp phaamylase,lipase). CoordinateSwallowing:CNSvoluntarycontrolto onguecontractshard palate,movesbolusbacksoftpalateisforcedupnasalregurgprevente ed (epiglottisisup).Medul llacontrolsstriatedmmco ontrolofswallowing. Trac cheoesophagealfistula (1:3000) Goe estotrachea/bronchus ha aveothermidline anomalies(espcardiac), Canleadto iration/pneumonia, aspi elec ctrolyte/fluid imbalances Congen nitalDuplication (Foregu ut)Cysts Asxorcompressive. c Saclike,cysticmass,2 mmlaye ers.Adjacentto orintramural.Ddx broncho ogeniccyst (cartilag ge) Atres sia

DiaphragmaticHernia(1:2000) Defectivediaph hragmclosure.Unilateral,most Lposterolateral.Portionofleafisabsent. Abdominalorga ansherniatedinto/fillthe thorax.Lungsare a compressedduring development lethalrespiratoryproblem msif large(especially yleftsided).Lunghypopla asia (bilaterally).He eartdisplacedright.

Webs Upper,thin,sem mi circumferential. Mostlyin 40+agedfemale e. PlummerVinson n syndromeIron deficiency /cheilosis anemia/glossitis/

Rings ,circumferential Lower,thick, A(abovesqu uamocolumnar junctionof stomach)orB(at esophagus/s GEjunction) Submucosalsoft tissueledges scoveredby mucosa

Steno osis
uscularis kenedwallw/atrophiedmu Thick propr ria.Mostareduetosevereinjury& inflam mmationresultinginsubmucosal scarri ing. Canresultfromchronicreflux,irradiation, i ticinjury,scleroderma.Canalsobe caust conge enital.

Congenital anomalies

mplete Incom devel lopme ntthin t cordor blindpouch

Hiat talHernia:Diaphragmcrur rawidelyseparated; wide enedspace.Mostlyinadu ults. Sliding(Axial,95%);stomachslides abovethediaphragm.Bellshaped tationabovediaphragm.Sx S dilat reflu ux,heartburn.Complicatio ons ulce erate,bleed,perforate. Para aesophageal(nonaxial):st tomach port tionbulges,wedgesintowidened w spac ce.Canstrangulate,obstru uct.

DiverticulaOutpo ouchesofGItract Epiphrenic diverticulum justaboveLES nocturnal fluidregurg Traction T diverticulum: d not n amotility disorder d midpoint, no n sx.Inflammation (TB, ( histoplasmosis) Pulsion P diverticulum: dysmotility d Zenkers diverticulum d just aboveUESDysphagia, egurg,neckmass. re Aspiration A pneumonia p

Lacerations(MalloryWe eiss) MalloryWeisslongitudin naltearsatGEjunction,cardiaHxofsevere/prolon nged vomiting/retchingRisk kw/acutealcoholintoxicat tion,Hiatalherniapredispo oses. Theorythatmmdoesno otrelax.Refluxinggastricc contentsoverwhelmthega astricinlet contraction.Causesmas ssivedilation,tearing(Injuryfrombelow) Grosslinearlacerations atemucosa.Usuallysuperf ficial.Microscopic s,mmtocmlong;penetra traumatichemorrhage andacutetissueinflamma ation. atemesis Sx:UpperGIbleed,hema Rx:generallydontrequiiresurgery,healingtendst toberapid/complete. ome=distalesophagealtra ansmuralrupturew/media astinitisafter Ddx:Boerhaevessyndro vomiting

Obstruction, MotorDysfx

Vari ices Tort tuousdilatedsubmucosalveins. v Bulgeintodistaleso ophageallumen.Collateralchannels betw weensystemicandportalveins. v Prol longed,severeportalHTN(cirrhosisdevelopin90% %ofcirrhosispts,hepatic schistosomiasisis2ndmostcom mmoncauseworldwide). matemesis).Complications4050%mortalityin1st time. Asxuntilrupture(massivehem %rebleedin1yr.Somemortalityperepisode.Ballo oontamponadeorscleroth herapy 50% usua allyused(dontspontaneo ouslysubside).Canseehep paticencephalopathy Candetectw/hepaticvenogra am

Achalasia FxobstructionofLES(doe esntrelax)hastone,a aperistalsis.Proxesophaguspainlesslydilates.Canb befromdamaged myentericplexus,lowVIP P Causes:Primarilyunknow wn.Likelyrelatedtodysfxo ofinhibitoryneuronsw/NO O,VIPindistalesophagus.Secondarycauses (rare)surgery,infiltrativ vedisease,Chagas(T.cruziiidestroysmyentericple exus) Sx:progressiveDysphagia a,nocturnalregurg,wtloss s.Wallhypertrophiesthen nthinsasesophagusprogr ressivelydilates. Mucosaisnormalinflamed,ulcerated,fibroticas sdiseaseprogresses. Complicationspulsiondiverticula d (epiphrenic),squ uamouscellcarcinoma(5% %),infection,aspiration,ca andidaesophagitis Rxlaparoscopicmyotom my+balloondilatation.Bo otoxinjections.

EsophagusPat thology,continued
Refl luxgastritis(GERD): BarrettEsophagus Infectious/Ch hemicalEsophagitis contentsinto intestinalmetapla asiadistalpaletan refluxofgastricjuices/c Irritant ts:corrosivechemicals,pills,hotliquids, loweresophagus.Patho ogenesisfactors squamousepithel liumisreplacedby heavys smoking. M Morphology:columnarintestinal thatexposuretogast triccontents. metaplastic(velv vetyred)intestinal Infectio ous:candida,HSV,CMV(nuclear t typeepithelium.Admixedgoblet Contributingfactors antireflux epithelium.Aresponsetoprolonged inclusio ons) c cellsrequiredtomakedx.Caution reflux.~10sxGERDptshavethis. mechanisms.LESton ne, Iatroge enic:cytotoxicchemotx,radiation,blood endoscopicabnormalitya also Riskfactorforade intraabdomainalpressure.Eatingahigh enocarcinoma. vesselinjury n neededfordx.Complicatio ons fatmealcancontributebycausingCCK Sx:mostage4060, 6 GERDsxw/local Eosinophilic:numerouseosinoph hilsin u ulcer,stricture,adenocarcinoma. release(whichgastricemptying, ulceration/bleedin ng/stricture liumespeciallynearthesurface.Sx epithel LEStone) Dysplasiaprecede esadenocarcinoma. adultD Dysphagia,foodimpaction. Sx:Dysphagia,heartbur rn,regurgorsour Cytologicatypia(n nuclear Infants s/childrenhavefeedingdifficulties, fluid,hematemesis,melena(maybe characteristicsla argenuclei, GERDl likesx.Noresposetolowdoseproton ck) cytoplasm,mitoses)+architectural mistakenforheartattac pumpi inhibitors,noacidrefluxon ntesting.Hx SR(transientLESrelaxation n)occurs TLES atypia.Lowgrade Gross:hyperemia echangeslesssevere ofatop py(allergies,asthma,blood deosinophilia). independentlyofswallowing,may m beassociated ialinflammatory thanhighgradech hangesinwhich Microscopic:epitheli Txav voidfoodallergens,corticosteroids.Ddx astricdistention,neutrallymediated.HaveLES w/ga cellsespeciallyeosinoph hils,neutrophils; architecturalatyp piaisgreatest. reflux x, relax xation for 5 30 seconds. N ormal physiological elongationofpapillae(t toupper1/3 Architecturalchan ngesofdysplasia= Intram mucosalcarcinomaglands sbreachthe even ntswallowlotsofairbelch, b preventsgastric epitheliumnormalisto t lower);basal nuclearcrowding, ,stratification,gland baseme entmembranebutdonotinvadeinto bloating.Triggeredbygastricdistention, d pharyngeal cellhyperplasia(>20%of o epithelium inglandformation,nobasement submucosa mechanicalstimulationwhichcauseavagalreflux. normalis1015%) h. membranebreach Esop phagealcarcinomaaden nocarcinoma: Squamouscellca arcinoma: incid dence,especiallyin= Chronices sophagitiscausescellturnover. Risk k:w/documenteddysp plasia.Alsotobacco,obesity,radiationtx. Gross:70% %inupper2/330%inlow wer1/3.Squamousdyspla asia Grossearlyflatpatchesmasses m infiltrate,ulcerat te.MostariseinBarrettsesophagusatGEjunction. Earlywhit teplaque,beginsasanintraepithelialneoplasia.Lat tergeta Microscopic=intestinaltype.Mucinproducing,glandfo orming.Adjacentdysplasia a.Glandformationandmucin massthat invades,encircles,constric cts.Mayulcerateordiffus sely prod ductionidentifyamalignan ncyasanadenocarcinoma.welldifferentiatedhavemore,poorly infiltratew wall. diffe erentiatedhaveless. Microscop picmostaremoderatelyt towelldifferentiated.Ker ratin Path hogenesis:Refluxbarre ettsdysplasia(criticalst tep)adenocarcinoma.Stepwise S accumulationof production n,lackofglands/mucinide entifyamalignancyasasqu uamous gene eticandepigeneticchange es.Duetochronicdamage etocellsandDNA.Metapl lasiacellproliferation, , cellcarcino oma. Dysp plasia%cyclingcellslossofcellcyclecontrol. . Sx:Classic callyhasinsidiousgradualt tumorgrowthlateDysph hagia obstructio on.Dietchangeofsolidsto oliquids.Extremewtloss.Usually tumorswhensx,oftenmet tastatic. verylaget Complicatiionsdebilitation,ulceration(hemorrhage/sepsis,fo ood aspiration ifcancertracheoesophage ealfistulaforms. MaleHot ttea,carcinogens(otherco ountries);smoking/alcohol(here)

Esophagitis
Inflammation ofesophageal mucosa In5%ofadult population, morein northernIran, partsofChina

Neoplasms

Stomach
NormalStomach: Allgastricsurfac cecoveredbyfoveolarglands.Deepglandstypevaries byregion;deepglandmucusmadeincard diaandpylorusisdifferentfrom mucusmadeinf foveolarglandsthatprotectsmucosafromaciddiges stion. Saccularvolum me=12001500mL,butcandistendto3000mL+. Mucouscells:in ncardia,antralregionsec cretemucus,pepsinogenII I. StimulatedbyAch,Prostaglandins Parietalcells:in nfundus,bodyveryeosin nophilic.HaveanH/KATPa ase. SecreteIFtobin ndVitB12forabsorptionin nileum,gastricacid. Chiefcells:Secreteproenzymespepsinoge enI/II(activatedtopepsinin pH<2).Verybas sophilic. Endocrine/enter roendocrinecellstriangu ularshape, o Gcellsinantrum(makegastrin); o enterochr romaffinlikecells:makehistamine, h bindH2recepto orsto causea acidproduction. o Dcells:m makesomatostatin(inhibits sGcellsecretionofgastrin and parietalce ellsecretionofacid).SecretionofinhibitedbyAch. o Xcells:makeendothelin MucosalProtectivemechanisms: Epithelialcellss secretebicarb(sopHisneu utralnexttoepithelium),quickly q replaceepithelia alcellsviarestitution,high hbloodflowremovesacidand a restoresbicarb, PGsfavormucus/bicar rbproduction;inhibitparie etalcellacidsecretion,imp prove mucosalbloodflow. SecretionofAcid d: Cephalicphase: p initiatedbytaste/sight/smell/chewing/swallowingoffood(vagalmediat tion).Accountsfor3040% %ofacid secretion.StimuliactivateCNS,activatevagalefferentnnwhichstimulateneuronsinEN NStoreleaseAchorGRP(g gastrin releasingpeptide). p InhibitedbySNS S.Acidislowinitiallyfollow wingamealbecausethisre esponsetakestime. Gastricph hase:stimulationofstretch hreceptorsgastrinreleas sepromotedbyluminalaa as,vagalmediation.Accou untsfor 50%ofacidsecretion.Gastricdiste entionactivatesmechanore eceptorstoinitiatelocal/v vagovagalreflexes.Gcells sdirectly activatedbypeptidesaswell.Inhibi itedifgastricacidfallsbelo ow3(somatostatinrelease edunderacidconditions) Intestinalphase:foodenterssmallintestine i 10%ofacidsecretion.Stimulatedbycircu ulatingaasandaasinintes stinal lumen.Pa athwaynotreallyknown.Inhibitedbyacid,fat,hype ertonicsolutions. Allsignals sleadto:Activationofprot tonpump o Ach hfromvagalafferentsstimulateM3cholinergicrecep ptors(activatesPIpathway y,bringCa++intocell,activ vateH2 pum mp) o Gas strin(stimulatesCCKbwhic chactivatesPIpathwaytobringCa++intocell,activa atesH2pump)somatosta atin inhi ibitsgastrinrelease o Hist tamineworkssynergisticallyw/Ach/Gastrintoreleas seH2(stimulatesH2recept ptors,activatesadenylatec cyclase, cAM MPthisisthemostimportantfactor)PGE/Iinhibi ithistamineeffectsbybloc ckingcAMPviaGiactiva ation

Ittakes9.1kcaltosecrete1molofHCl

Antralmucosa

Fundicmucosa

Gastricmotility: Proximalstomach:storage/retentionoffood o Gastricrela axation:receptiverelaxation/accommodationoccursasmealenters.Vagalfibers(viaVIP, ,NO), secretin,GI IPregulates.Thefundusrelaxe eswithaswallow.Avagotomy ywouldcauseaninhibitionofbeing b able torelaxyou urstomachupontakinginame eal! Distalstomach:grinding/mixingfoodhasslowwaves w (BER)andperistalsis o Gastriccon ntraction:pacemakercellsbetw ween2mmlayers.BERstartin ngreatercurvatureofstomach handoccur throughout tGItractkeyinregulatingwh henacontractioncanoccur.ABERisintrinsicrhythmicalfluct tuationin restingmem mbranepotentialofGIsmoothmmcells.SlowwavesstartininterstitialcellsofCajalandar realways presentth heydictatewhencontractionscanoccurandarentalteredby yhormones/nts.Instomach,BER= B 3/min (12/minind duodenum,9/mininileum,3/6 6incolon).Mmcontractionisinitiatedbyspikesrelatedto intracellularCa++andoccuronlyduringth heplateauofslowwaves.Inte ensity/frequency/durationofsp pikes determines samplitudeanddurationofmm mcontraction Eo osinophilicgastritis:idiopathic ceosinophils in nfiltratestomachwall(especiallyantrum, py ylorus).Txsteroid. Allergicgatroenteropathy:inkid dsdiarrhea, vo omiting,growthfailure,eosinophilsinbiopsy of fantrum. Ly ymphocyticgastritis:Tcells(CD D8)inbodyof st tomachcausesabdominalpain,anorexia, na ausea,vomiting.~60%assocw/celiac w di isease. GranulomatousGastritis:intram mucosal ep pithelioidgranulomasfromCro ohns, sa arcoidosis,infection,systemicvasculitis, v or re eactiontoforeignmaterial. Acute: Acutemuc cosalinflammatoryprocess(tra ansient). Seeneutro ophils(epithelium),congestion, , edema,ero osion,hemorrhage. Outcometransient(healsorfatal).May y progressto oacuteulcers. Pathogene esismultiplesynergisticfactor rs. Associated dw/heavyNSAIDuse,alcohol(t tendsto causehematemesis),smoking,severe physiologic cstress. Sx:asxorvariable v epigastricpain,N/V.Bleeding, B hemeteme esis,melena(maybefatal).Ris skof progressiontodeepulcers. Peristalsis:initia ated/regulatedbyinterstitialce ellsofCajalinmidportionofgr reatercurvatureofthestomach.Mm contractionsocc curwhenspikepotentialsappe earduringdepolarizingphaseo ofBER.Probabilityofcontractionbyvagal readingofslow stimulation.The ereisuniformBERfrequencyingastricmotorcells,butapha aselagoccursfromdelayedspr waves ndingoffood. Antralsystole:P Pyloricsphincterpartiallyclose esduringperistalticwaveandr retropulsioncausesmixing/grin Liquidspassthro oughpyloricsphincterandent tertheintestine,butfoodcant tpassthrough. enosiscanaffect Pyloricsphincte er:regulatesentranceintointe estinefromstomachbyparticle esize.Gastriculcers,pyloricste this. Migratingmoto orcomplex:migratesfromstom machtoterminalileum.Occursevery90minutesintheinterdigestiveperiod. o Excitatory:Ach(viaCa),Su ubP(via rma,muscular Sweepsoutthe GItract.Canhaveemptyingaftervagotomy,w/diabeticg gastroparesis.Alsoinscleroder Ca).Inhibitory:VIP(via cAMP), dystrophy.e emptyingcanhappenw/gastrec ctomy(dumpingsyndrome)VIPduetofoodinduodenum, NO(viacAMP) enterogastricre eflex. Chronic:Theprese enceofchronicmucosalinflam mmatorychangesleadingevent tuallytomucosalatrophyandi intestinalmetaplasia(usuallyw withouterosion). Seelymphocytes,plasmacells(laminapropria),neutrophils n (epithelium).Intes stinalmetaplasia/atrophy(from mdamagerepair). Outcomenottransient.Mayprogresspeptic culcercarcinoma,lymphoma. PathogenesisHpylori,NSAIDs. Individualsrespon nsedeterminesriskacid(a antralgastri s)pepticulcera ation.acid(pangastri s) atrophymalignancy. H.pyloriGramneg. n Flagellahavemotilityinmucus.Adhesinsadhereto surfaceoffoveolarmucuscells.Notinfociofint testinalmetaplasia.Adaptedt to s). Autoimmunegastritis schronicatrophicpangastritis(rare<10%chronicgastritis lethalgastricacidurease(ureaNH4+CO2 2),buffersnearbyacid.Express ss sparietal CD4mediateddestructionofparietalcells.D Diffusedamagetobody/fundus toxins(CagA).Ant trumiscommoninfectionsite, ,besttobiopsyearlysee (oxyntic)cellshypochlorhydria/achlorhydria agastrinproducingcellsinantrum erythematousmucosa.Later,coarse/thickenedrugalfolds,evennodular.Late est hypergastrinem miaECLcellhyperplasia riskofcarcinoidtumor. atrophy.Micros scopic(biopsy)seeorganisms sONfoveolarsurfaceandneck k cells,IF. Intrinsicfact tor:B12deficiencyriskperniciousanemia.Absagainstparietal p cellMUCUS.Canbeseenw/H/E,Giemsa,silverstains.Neutrophils(epithelial) ) stritis00 Chronicpangastritismucosalatrophyw/intestinalmetaplasia.Chronicpangas andplasmacells(laminapropria).lymphocytesandaggregregatesw/germi nal astri span body/fundusareinvol lvedparietalcellmass(atrop phy),acid.Hpyloriantralga centers(inducedMALT). M Noninvasivetestdetec ction=ammoniuminbreath, bacteriainfeces,abs a inserum

Gastritis
Inflammatory responseto mucosaldamage bygastric secretions following disruptionof protective mechanisms

Gastroenteritis

Viral:secretorywaterydiarrhea.Stomach(n/v),smallintestineinvolved.Shortened/spruelikevilli.Lymphocytesinlaminapropria.Brushborderlost,vacuolesinsurfaceepithelium.Cryptshypertrophied

Stomach,Cont tinued
Gastriccongenitalano omalies Heterotropictis ssuerestsgastricsmallpatchinintestines,especiallyMeckelsdiverticulum.Bleedingfrompepticulcerationofadjacentmucos sa(canmakeforconfusing g dxsincethistissueisinab bnormallocation) Pyloricstenosis:muscularispropriahypertrophy+edema+inflamm mation.M>F;infamilies,23wkoldinfants.Projectilenonbiliousvomiting.PEfirm,ovoidpyloricm mass.Txsurgicalmmsplit tting.Inadultscanbeacqu uiredwithcancer,seconda aryfibrosis. Acu utegastriculcers: PepticUlcers astritis. samecausesasacutega Deepchroniclesionsmostlyassocw/H.pylor riinducedhyperchlorhydricchronicgastritis.100%of o CriticallyillICUptsstr ressulcers PepticUlcer duodenalulcersH.py ylori,70%gastric(antral)ulcers u Hpylori(butonly1020%ofthoseinfectedw/H H Happenwithseverephy ysiologic Disease pyloridevelopulcers) ).Resultfrommucosalbre each(+exposuretoacid/pepticjuices);cofactors stressshock,sepsis,burns,trauma (chronicNSAIDuse,smoking, s highdosecorticosteroids,psychologicstres ss).w/ZES(highgastrin (Curlingsulcer)inpro oximal secretionbytumorca ausesacidity) duodenum. 98%induodenumorstomach(4:1). urgery,tumor intracranialinjury,su o Duodenalinanterior a wall,nearpylorus. (Cushingsulcer)esop phagus, o Gastricinless sercurve,antral,nearbody. stomach,duodenum. o Size<2cm.if<0.3cm,shallow;>0.6cmdeep.Single80%.Roun nded,sharpedges.Wall Morphology:multipleabrupt esmooth/clean,withblood dvessels(sometimes straight.Marginlevelw/mucosa.Base lesionssmall,<1cm;circular. c thrombosed).Theyhaveapunchedout tappearance. Normaladjacentmucos sa.Superficial Microscopicmorphology: erosionsorfullthicknes ssulcerations. o Acute:surfacenecroticdebrisneutrophilinfiltrate Black/brownbasedueto t acid o Chronic:deepgranulationtissue,deepe estscarandthickBVsadjacent a chronicgastritisis s digestionofblood.Noscarringor almostalwayspresent.Ulcerdepthvarie essuperficialtodeeppen netrationintowallor thickenedbloodvesselinulcerbase. subjacenttissuesperforationcanhapp pen. merosionerosiondoesn ntbreachmuscularismuco osa. Ulcerdifferentfrom Completelyhealindays sweeksif Clinicalfeatures:mid ddleaged/olderadult.Epig gastricburningpainseve eralhourspostmeal,worse NSAIDs:suppressmucosal m Pgsynthesis,aspir rindirectlyirritates causeisremoved. atnight,betterw/eat ting/alkali.N/V,belching/bloating,wtloss,microcyticanemia(irondeficiency) ), Cigarettes:impairhealing/blood h flow Tx:14%needtransfusion.Correct evidenceofbleeding/ /perforation.Perforatingulcers u mayradiatetoback, ,LUQ,chest CRF,hyperparathyr roidism:moreulcersbeca usehypercalcemiastimula atesgastrin underlyingconditionsto otx.Bestto Tx:eradicateHpylori i,acideffects.Surgerymay m beneededforbleedin ng/perforationlesions production.Nogen neticlinkstoPUD. useprophylaxistoprevent. HypertrophicGastropathy: Gastricdilation: :fromgastricoutletobstru uctionorfunctional Gastricvaric ces: Conditionsw/gia antcerebriformrugalfoldsepithelialhyperplasia a,noinflammation.Mimics atonyofstomac ch/intestines(paralyticileu us).Canleadtogatric Happenw/portalHTN(but carcinomaandlymphoma. rupture.(canha appeninnewbornduringl abor,w/severe lessthaneso ophageal vomiting,cardio oresuscitation,afterlotsof fcarbonatedbeverage varices.).Mostwithin23 Variants: intake. cmofGEjun nction,rarely acidsecre on nriskpep culcer.reallyhighhyperplasiaofparietalcellsZollingerEl llison occurwithou utesophageal Syndrome:duet togastrinriskw/MENI(gastrinsecretedbynon n Bcelltumorofpancrea as) Phytobezoars plantmaterialconcretion inthestomachthat varices(soyoucanavoid acidsecre on nnoriskulcer;sec cretedmucus.ReallyhighhyperplasiaofFOVEOLARcells. cantbedigested d gerousbiopsy doingadang Lotsofmucus+deepglandatrophy.Happ pensw/Menetrierdisease: :M>F,30s50s.duetoexc cess onthese. TGFa.Protein/wtloss,diarrhea,riskof fadenocarcinoma. Trichobezoars hairballs Hyperplasticpolyps(75%): Fundicglandpolyps s(prevalence): Adenomas(~10%of fpolyps): G Gastric Hyperplasia,su urfacecells.Antrum,chron nicgastritis.Multiple,mos st Fundus,cysticglands.Singleormultiple.F,pr rotonpumpinhibitors. Neoplasm,intestinal lcells.Antrum,chronicgastritis.Single;<2cm.Sessileorw/stalk. Polyps n) <1cm.Sessileorw/stalk Seenw/FAP(familialadenomatouspolyposis) AllhaveDYSPLASIA( (>2cm).~30%harborcarc cinoma.Seenw/FAP(colon homa A Adenocarcinoma GIST(G Gastrointestinalstromaltu umor) Kaposissarcoma,MALTlymph nsiteof Canpenetratethroug ghwalltoserosa.Theyme etastasizetoregionalthendistantlymphnodes.Virc chowssupraclavicularsen ntinellymph T Tumorofinterstitialcellso ofCajal(which Stomachismostcommon nodeisoften1stsignofmalignancy.AlsoSister rMaryJosephnoduleofperiumbilical p regionsignofmetastaticcarcinoma(> >50%ofcases c controlGIperistalsis).50% %ofthesetumors extranodallymphomas.Mostare areGIcancers) a areinstomach. MALTlymphomas.Stomacharise Canextendtoadjacentorgansduodenum,pa ancreas. A Age:peak60yrs,M>F. whereMALTisinducedby b pro Widespreadtumorse eedingcanoccuronperitonealsurfaces M Mostlysolitary,canbemul ltiple.Protrude lymphomatousinfection.AllareB Tumors: Distantmetastases:liver,lung,ovary,Krukenbe ergtumor(signetringcellcarcinomabilateralova aries) in ntolumenorserosa.Cuts surfaceistan celltype. Gastric n nowhirlingsmoothmm,he emorrhage Mostareassociatedw/chronic In ntestinaltype:(likecoloncancer) c Diffuse D type: carcinoma c common. gastritis(Hpylori). Histologyglandform mation,mucin.Growth/invasionbulkytumor,inva adesalongbroad poorlydifferentiatedsingle especiallyhigh M Microscopic:elongated,thinspindlecells Ifnotassociatedw/Hpylorithencan front.Predominatesinhighgeographicalriskareas.Developsfromprecu ursorlesions,M>F. dyscohesivecells(signetring). inJapan,Chile, o orplumpepithelioidcells(ormixture). begenetranslocationt(11,18), Mostinantrum,onle essercurvature.Grosspat ttern:focallesion.Exophyt ticmassorulcer,flat Growth/invasiondi iffusely CostaRica, seNFkB P Prognosislocation/size/m mitoticindex t(1,14),t(14,18).Allcaus (early). infiltrating.Noprecu ursorlesion. Colombia, ell p predictaggressive.Gastric conesareless activation(promotesBce Risk:Hpylori,diet,cu ulinaryprocesses,lowSEst tatus,smoking NogeographicalriskM=F.Gross China,Portugal, oticscure50% a aggressivethansmallintes stine. growth/survival).Antibio Genetics:FAP,othermutationsofcoloncancerassociated pattern:entirestoma ach.Cells Russia,Bulgaria, vancedor R Recurrence/metastasisisu unusualif<5cm lesslikelyiftumorisadv permeatewallinsidio ouslyinsingle moreinlower + raremitoses,butlikelyif>10cm+lotsof aggressive. fileorsmallclusters.Thickwall, SEgroups.M>F m mitoses. Morphologythickenedmucosalfolds flattenedrugalfolds.Desmoplastic (2:1) G Genetics:95%cKIT+(CD11 17).70%are andcentralraggedulcer.Initially responseresultsinRIGID R WALL C CD34+thatshowdifferen ntiatefrom involvesmucosaandsubmucosathen (leatherbottlestom machlinitis le eiomyoma destroyswallstructures.Microscopic plastic) 8 85%havecKITorPDGFRA Abothactivate lymphocytesdenselyinfiltratelamina Riskw/chronicpangastritis m. T TKsignalingpathwaytopr romotecell propria+glandepithelium (multifocalatrophyw/intestinal w p proliferationandinhibitap poptosis Lymphoepitheliallesiongland metaplasia),adenom mas. T Tx:imatinib(TKinhibitor usein destructionbyabnormallymphocytes. Genetics:lossofEca adherinfx, u unresectable,recurrent,metastatic Cellmarkers:CD19/20+ CDH1mutation d disease) Youllloseperistaltic ate fxobstructionperfora

Small/LargeIn ntestinePatholog gy
Gas strin Act tion:H+secre onbyparietalcells,S mulates gro owthofgastricmucosa Stim muli:Gcellsofantrumsecreteinresponsetoameal phenylalanine,tryptophan,stomachdistention,vagal stim mulationmediatedbyGRP. Inh hibition:H+instomachlum men,somatostatin GIHormones Pep psinogen/Pepsin Sec cretedbychiefcells toh hydrolyzeproteins top peptones. Stim muli:Gastrin,Ach, sec cretin Cleavedtopepsinat pH< <2 HistamineAction n:directlygastricH+ secretionStimuli i:Mastcellsofgastric mucosarelease VIP Action:relaxesGIsmo oothmm(LES), pancreaticbicarbs secretion,inhibits gastricH+secretion. Stimuli:Releasedfrom mneuronsin mucosa/smoothmm ofGItract GRP(Bombesin) Actio on:gastrinreleasefrom m Gcells Stim muli:Vagusnnthat innergateGcellsreleaseit Enkephalins Action:StimulateGIsm moothmm contraction(LES,pyloric,ileocecal sphincters),inhibitintestinal secretionoffluid/elec ctrolytes

CCK GIP Somatostatin Secretin Action:Contractionof o gallbladder,relaxationof o Action:insulin Action:inhibits Action:WorkstoH+in nlumenofsmall SphincterofOddi,Pa ancreaticenzymesecretion n, release,inhibitsH+ releaseofallGI intestinepancreaticbicarbsecretion, helpsbicarbsecretion nfrompancreas,growthof o secretionbygastric hormones, growthofexocrinepan ncreas,s mulates exocrinepancreas, gastricemptying(more parietalcells inhibitsH+ water/bicarbexcretionfr romliver,bile timetodigestthefat ts) Stimuli:Duodenum, secretion production,inhibitsH+se ecretionbygastric Stimuli:Icellsofduodenum/jejunumrelease jejunumreleasein Stimuli:H+in parietalcells whentherearesmall lpeptides/AAs,FA, responsetoFA,AA, lumen Stimuli:Scellsofduoden numreleasewhen monoglyceridesNOTtriglycerides(theydont ORALglucoseload Inhibition:Vagal H+/FAinduodenallumen n crossintestinalcellmembranes) m . stimulation Sensorynn:cell c bodiesinnodosegangl lia(vagalafferents)andspinal(DRG)ganglia.Convey ysensoryinfotoCNS (chemo/noci/ /mechanoreceptors)Meissnerssubmucosalplexus scontrolssecretion/blood flow Entericnn:Uselocalreflexestorelayin nfointheGItract.Myente ericplexus(Auerbachsplex xuscontrolsmotility) Locatedbetw weenlongitudinalandcircu ularmmlayers. Excitatory:Ach(intracellularCa++ C tocausecontraction). Inhibito ory:NO(smoothmmcG GMP),VIP(smoothmmcAMP) c Parasympatheticnnexciteente ericnn Sympat theticnninhibitentericnn n Enteroendocrinecells: Enterochromaffincellsinmucosa asensorydetectors,relea ase5HTactat5HT3rece eptorstocause excitation/activationofmotorreflexes. Motilin ninitiatesMMC Parasympath heticnn:Usuallyexcitatory yonGItract.Vagusnnand dpelvicnnAchisnt,stim mulatesmotility.

Sympatheticnn:UsuallyinhibitoryonGI G tract.Fibersoriginatebe etweenT8L2.Postganglio onicnninceliac/superior mesentericga angliaandinferiormesentericgangliaNEisnt,inhibitsmotilityandsphinc ctertone **BothPNSand a SNSsalivation. MigratingMoto orComplex Localintestinalmotility: o gastrointestinalmotility,severalhours Localcontract tionsexposeintestinalcont tentto Cyclicpatternof afterameal.Cy yclefrequency=7580min n.Actsasa enzymesandabsorptive a surface.Tonic housekeepertosweepstomachandcle eanupsmall contractionsseparate s boluses.Peristals sis intestineafterdigestive d phase.3phases: propelsintestinalcontractionsovershor rt Phase1:little/nocontractileactivity(10minute distances duration) ) Phase2:intermittent/irregularcontractileactivity (60minduration) d Phase3:strong,slowlypropagating g,startin antrumand a gototerminalileum.Preceded P byrise inplasma amotilin(initiatesMMCin antrum/d duodenalregion) Ifthisisntwork kingwell,canhaveintestin nalovergrowth insmallintestin ne.

Ileoce ecalreflex: contro olsmovementfromsmallintestine colo onandpreventsrefluxofc content backin ntosmallintestine Rectosphin nctericreflex,defecation: Movementofcoloniccontentsintorectumdistends axationof it,initiatesr reflexcontractionsandrela ncterhas internalana alsphincter(externalsphin ppropriate) voluntaryco ontrolandrelaxeswhenap

Gastricemptying: coordinationofantralcontractionand pyloric/duodenalrelax xationhastohappen together.Reflexcontr ractionofantrumis mediatedbyAch,refle exrelaxationof pylorus/duodenumism mediatedbyNO. Sometimesdiabeticsh havedeficitsinNO containingnn,sotheyhavedelayedgastric emptying.Evenduring gfastingcontractionsever ry 90minutesclearoutst tomach(motilinmediates) )

Segme entingcontractions:lowfrequency, propellcontentslowlytoallowe enhanced water absorption Massm movements:13timesada ay, contra actionsstopandthereisst trong waveo ofpropulsivecontraction. Gastro ocolonicreflex:feedingstimulates coloni cmotility(mayinvolveext trinsic nerves sofPNSaswellasCCK)

Small/LargeIn ntestinePatholog gy
Smallintestine: 6mlengthduodenum m (1st25cm retroperitoneal),jejunum (inperitonealcavity, transitionstocolonat ileocecalvalve). Mucosa:Villicryp ptheight4:1. Duodenum mhas submucosa alBrunner glands(sec cretebicarb, glycoproteins, ppesinogen nIIlike pyloricmucusglands) Columnarabsorptive a cells(dense ebrush bordermic crovilli, terminalweb) w Goblet cells(secre etemucin) Endocrinecells Panethcells:eosi inophilic, secreteantimicro obialproteins (defensins) Largeint testine(colon):1.5m retroper ritonealinascending anddesc cendingportions (accesso orybloodsupplyfrom posterio orabdominalwall). Function ntoreclaimluminal water/electrolytes. Mucosa:hasnovilli,few wer microvilli,gobletcells,,isflat. Hasstraighttubularcryp pts thatextendtomuscular ris mucosa.Regenerateswell w (allisrenewedevery46 dayssorepairswellbu ut alsoverysensitiveto radiation/chemo) Cecumascendin ng: suppliedbySMA Transverse descendingsigm moid: suppliedbyIM Rectum:Sigmoid dcolontransitions torectumaround dS3.Upper suppliedbysupe eriorhemorrhoidal branchofIMA.L Lowersupplied byhemorrhoidall branchofinternal iliacorinternalp pudendal. Peristalsis s anterogradeand retrograde emixesfood,helps nutrientab bsorption. Mediated byintrinsic Meissnerp plexus(baseof submucosa a),extrinsic Auerbachp plexus(between innercircu umferetial/outer longitudina almm) Colon Absorb:Water,NaCl(butmosthastobedoneinsmallintestineoritsoverwhelmed) Secrete:Bicarb,K+(d diarrhealeadstometabolicacidosis,hypokalemia) DOESNTabsorbcarbs,fats,orproteins

Normal

Duodenum: Hypertonicfluidenters s,becomesisotonic(some ewater secretedintolumen) Absorb:Divalentions,Fe,watersolublevitamins s

Jejunum m Absorb: :water/electrolytes(much hlikeproximal tubuleinkidney)

Ileum Absorb:water,Na+,Cl,K+,BILE B SALTS,IF/B12 Sec crete:bicarb

Lip pids: Dig gestion: Gastriclipase(chiefcells)secretedwhenstimvia aAch,gastrinoptimalatpH26. Activeinstomachandduodenum.Hydrolyzespo osition3ofTGtomakeFA A/DG Antralsystoleformsemulsion Absorption: Acid+secretinfromScell+bicarbfrompan ncreaticductpH(6.5) FACCK(duodenalendocrine e cells)enzyme essecretedfromacinar cells/gallbladdercontracts/Oddirelaxes. Bileacidsemulsifyfatsso olubleinwateratintestina alpH,nopassiveabsorptionin bili iarytract,limitedpassiveabsorption a insmallintestin ne.Ifamidatedresistant tto hyd drolysisviapancreaticenzy ymes,passiveuptake. Pancreaticlipaseshydrolyz zelipidstosmallerforms(F FA,monoglyceridesinact tivatedby gastricpH).OptimumpH=89or67ifw/bilesalts..pH<4inactivateslipase.Lipases are eboundtobilesaltsviaCO OLIPASE. Sol lubilizedinmicellesviabile eacids.Micellesformw/b bilesaltsinintestinallumen n, FA/ /monolycerides/cholestero olcandiffuseintocell,ree esterificationincellto trig glycerides/phospholipids.Chylomicronsformincell (requiresapoprotein)andare tra ansferredtolymph. Sho ort/mediumchainFATGsdont d requiremicelleform mationandlymphatictransportcan use eshort/medchainFAtotreatsteatorrheacausedby y fatmalabsorption. Fatsolublevitamins: ADEKrequireadequate lipidabsorptionsoany diseasethataffectsbile absorptionwillaffect these(VitAnight blindness,VitD osteomalacia,VitE hemolyticanemia,VitK PTT).Pancreatic lipasesremoveesters fromA/E.Thelipases removeestersfromA/E. Theyareincorporated dinto micelles,takeninvia passive diffusionorcarrierme ediated transport,andpackag gedinto chylomicronstocircu late. B12: Madeonl lybymicroorgs, suppliedb byanimalproducts Role:coenzymeforconversionof homocyst teinemethionine, methylma alonylCoAsuccinyl CoA. Sxofdef:megaloblasticanemia, neuropsy ychabnormalities(but youhaveyearsofstored) PepsinreleasesCobalaminfrom food(Gas strinaction) Cobalaminbindssalivary/gasticR proteinsi instomach

Car rbs: MO ONOsaccharidesabsorbedinsmall inte estineviaNa+dependentcotransport c (SG GLT1glucose,galactose),facilitated f diff fusion(fructose)

Proteins: Pepsinogen:activatedbygastricH+ +topepsin Pepsinworks w bestatpH13,denat turedif>5. Pancreati icproteases(endopeptidas sestrypsin, chymotry ypsin,elastase;exopeptida ases carboxypeptidaseA/B)activatedby b enterokinase Brushbor rdermembranepeptidases(aminopeptidase N,endopeptidases,carboxypeptida ases,dipeptidases) 4intracel llularpeptidasesdigestabs sorbed di/tripept tides Notneededforproteindigestion,but b helps. AAsabsorbedinsmallintestineviaNa+dependent cotranspo ort Di/Tripep ptidesabsorbedinsmallint testineviaH+ dependen ntcotransport

Pre egnancy:length/massofintestine, lengthofvilli,numberofvilli,and glusocseabsorption Old deragedeclineinglucose etransport, less sresponsivetodietarycha anges Pan ncreaticamylasehydroly yzesthe alpha14linkageofamylose/ /amylopectin

Chymosin ninneonateshelpsw/effectivedigestionof milkprotein

rokendown CobalaminRcomplexbr bypancreaticprotease,binds cobalaminbindsIF oakeinCblIF Carrierindistalileumto complex oredinliver AbsorbedCobalaminsto

Electrolytes: NaC Cl: Smallintestine:entersvianaglucosecotransport t,NaAAcotransport, NaH+exchange Colon:passivediffusion n,stimulatedbyaldosteron ne PumpedoutofthecellagainstECMgradientbyNa N Kpump(basolateral) K: Dietaryabsorbedinsmall s intestineviapassivediffusion d (paracellular). Activelysecretedincol lon(stimulatedbyaldoster rone).indiarrhea becauseofflowratede ependentmechanism.Sodiarrheacanleadto hypokalemia. Cl:AccompaniesNa+absorpt tionpassivediffusion(paracellular),Na+/Cl cot transport,ClHCO3exchang ge Secretedintolumenvia achannelsregulatedbycA AMP,Nafollowsvibrio upregulatesthis.

Small/LargeIn ntestinePatholog gy
Gas stroscisis Ompalocele Heterotopia H Malrota ation Dupli ication Atresiaw/obstructio on Abd dominalwalldoesntform intestinesdontretur rntoabdominal nor rmally.9Xmoreonrtside. cavityafterphysiolog gicherniation. pancreatic p or bowelfa ailstorotate atresia=failedforma ation.Faileddevelopment torvascularinsult Abd dominalorgansprotrude Abdominalcontentsprotrudethrough smallorlargebowelsaccular gastric, g properly ybefore/during infarctresorption.InvolveSB,rarelycolon.Duodenum= thro oughdefect.Umbilical enlargedumbilicalrin ng. orelo ongatedcysticstructures, anywhere a in returnof o intestinesto jejunum=ileum.Sin ngleormultiple(~10%).To otalabsenceorstring cor rdNOTpartofdefect. Coveredbyamnionsac. s Intestinesalways along gsideorincorporatedin intestines,12 abdominalcavityin likesegment.Includesimperforatemucosaldiaphragm/imperforate NO Oamnioncovering(bathed MALROTATED. wall cm c nodule weeks512+ anus.birdsbeaksi ign ina amnioticfluid). Additionalanomaliescardiac50%, NO Oadditionalanomalies. neuraltube40.High hmortality. HirschsprungsDiseaseCon ngenitalAganglionicMega acolon MeckelD Diverticulum AcquiredMegacolonoc ccursatany Mig grationarrest/prematuredeathofneuralcrestcells sthat Shortseg gmentform(moreinMALE ES)rectum+sigmoid Failedin nvolutionofvitellineduct(normally age. dev velopintocolonicneurona alplexuses.Ganglioncells sareabsent colon connects sguttoyolksac).Ariseon nanti Chagasdisease(los ssofganglia, int theaffecteddistalsegment t(MeissnersandAuerbach hsplexus). Longseg gment(moreinFEMALES)rectum+entirecolon mesente ericsurface. estroyedentericpllexuses). Me echunclearRETmutation nsinvolvedinallfamilialca asesand Dx:muco osalbiopsyabsentganglioncellsindistal Ruleof2 2s:In2%ofpopulation,2 length,within Mechanicalbowel obstruction som mesporadic.Variablepene etrance,M>F. segment.HE/immunohisotchemAChE A stains.10%of 2ftofile eocecalvalve,2Xmorecom mmoninmales. (tumor,inflammato orystricture) Unaffectedsegment:is i dilatedproximaltoobstr ruction, caseshav veTrisomy21. Ifsx,willbebyage2.Truedivertic culum(all Toxicinflammation n(IBD normalganglia,wallini itiallyhypertrophiesthendilates, d thins, Clinical:Present P inneonatalperiodfailuretopass layersof fbowelwallpresent).50% %contain UC>CD),Cdiff. distends,mayreupture e(cecum). meconium.Progressestoobstructiveconstipation.May heteroto opictissuepancreaticorgastric(bleed). Visceralmyopathy Dis stalsegmentisNOTinnerv vatedcontacted,hasnoganglion g haveabd dominaldistention. Mostasx x,incidental. Functionalpsychos somatic cell ls.Nocoordinatedcontrac ctionsfunctionalobstruc ction.Always Complica ationssuperimposedente erocolitis, Canbeco omeintussucepted,incarcerate, disorder invo olvesrectum fluid/elec ctrolytedisturbances,perf foration/peritonitis perforat te(causingbleeding) AfterantibiotictxusuallyfromtoxinsofClostridiumdifficile(butcan c happenanytimethereisseveremucosalinjuryas sinischemiccolitis,volvulus,necrotizinginfections).Acutecolitisw/anadherentlayerof Pse eudomembranousColitis inflammatoryce ells/debrisoversitesofmu ucosalinjury. Dxconfirmedby yseeingCdifftoxininstoo ol.Relapsein25%. Waterydiarrhea a(nowtloss),patchesofbandlike b collagendeposits directlyunderthesurfaceepithelium.Middleaged,,olderwomen. Col llagenousColitis Normalradiolog gic/endoscopicstudies,lym mphocytesinepithelium+mixedinflammationinlam minapropria. Chronicwaterydiarrhea(nowtloss)w/int traepitheliallymphocytes.AffectsM=F,associatedw/autoimmune w diseases(c celiacsprue,thyroiditis,art thritis,autoimmunegastrit tis). Lym mphocyticcolitis Normalradiolog gic/endoscopicstudies,lym mphocytesinepithelium+mixedinflammationinlam minapropria. AIDS:50% %getdiarrhealillness,malabsorptivesymptom.Probablyduetocoexistentinf fections,butproposeddire ectAIDSenteropathy Transplan ntation:pretransplantconditioninginjuressmallinte estinalmucosa.AcuteGVH HDcausessevereabrupto onsetwaterydiarrhea.Foc calcryptcellAPOPTOSISse een.Followsallogenicbonemarrow transplan ntskinandGItractaremostaffected.DonotTcells sattackagsonrecipientep pithelialcells. Mis scellaneousIntestinal DrugInducedInjury:Focalulceratio onwhenpilladherestomu ucosaandreleasesconten ntslocally(canhappenine esophagusw/dryswallows) ),enterocolitisoftenassoc cw/NSAIDs. Infl lammatoryDisorders Radiation nEnterocolitis:anorexia,cramps, c malabsorptivediar rrheafromacutemucosalinjury; i finallmatorycolitis maybeseenw/chronicradiationenteritis/colitis.M Mayhaveischemicfibrosis/stricture Neutrope enicColitis(Typhilitis):acu utedestructionofmucosaofcecalregionseeninneu utropenicpts.Impairedm mucosalimmunity+compro omisedbloodflowdamage Diversion nColitis:divertedstreamthroughiliumdeprivesFFAsupply.Fixedw/restoredfecalflowthroughcolon,e enemasw/shortchainFA. . SolitaryRectal R UlcerSyndrome:rec ctalbleeding,mucusfromanus,andsuperficialulcer rationofanteriorrectalwa all CeliacDisease LesionSBmucosais sflattenedvillusblunting ng,atrophy.Hyperplasticc crypts, Sensitivitytoglutenprot tein(wheat,oats,barley,rye). r Chronicdisease Dx:An ntigliadinIgA,Antitissue lymphocytesindama agedsurfaceepithelium(va acuoles).Laminapropriah has omysial(very impairednutrientabsorp ption.Sx/lesionimprovew/grain w withdrawalfrom transg glutaminaseIgA,antiendo lymphocytes,plasmacells,eosinophils,ms,m mastcells.Damageisgreat terproximally mination, diet specif fic),improvew/glutenelim (duodenum). s,butsprue Biopsy yidentifyclassicfeatures ges.Hxof Epi:MainlyinCaucasians(geneticpredispositionMHCIIDQ2orDQ8 likech hangesseeninotherchang Sx:GImalabsorption n,fatigue,wtloss,irondef ficiency.Chronicdiarrhea(steatorrhea). st isaclue. go ctwins,1 degreerelat tives.F>M,2060yo). immu unedisease,lymphocyticcolitis c haplotype;inmonozyg Thegreaterthelengt thofdiseasedbowel,thew worsethesx.Latentdiseas seifonlyhave Abo oveceliac,belownormal serology,silentifnosx. s testinal Pathogenesis:Tcellsaccu umulateinmucosa(CD8in nepithelium,CD4inlamina a Risk:Tcelllymphoma,smallint Infantsfailure etothrive,irritability/mm m wasting quamouscell propria).Gliadininduces sepithelialcellstosecrete eIL15activatesCD8, adeno ocarcinoma,esophagealsq Olderchildren: :shortstature,pubertyde lay,abdominalpain,N/V,constipation, damagescells,riskoflymphoma.tTGdeamimidatesgliadin(peptidesbind d carcin noma.Suspectrefractorysprue s behavioral/sinproblems seinspiteof toDQ2orDQ8HLArecep ptorsonagpresentingcells s.CD4recognize or. ca ancerifwtandGisxaris Extraintestinal:Dermatitisherpetiformiis,jointproblems,seizures s,apthrous mucosaldamage,BcellsantitTG,antiendomysiu um,antigliadin. dietre estriction. stomatitis,oste eopenia ARISK Tro opicalSprue Malabsorptionsyndrome eofpeoplelivingin/visiting gthetropics.Sx:onsetday ysafteracutediarrhealinfection.Bacterialovergrow wth.Rx:broadspectruma antibiotics,maypersistforyears.NOLYMPHOMA (Po ostinfectious) Morphology:likeceliacexceptlesionalsoin nvolvesdistalsmallintestin ne(megaloblasticanemiaislikelyduetoB12lack Wh hippleDisease alsx), Cause:Tropherymawhip ppelii(G+actinomycete)ca ausesraresystemicdisease eorgproliferate/accumu ulateinanytissue(ms). Caucasian,M>>F. Sx x:malabsorption,diarrhea,wt.Arthropathy(initia ve Pathogenesis:Nohostim mmunereaction,pathogenesisnotclear.GIsmallin ntestinelaminapropria+mesenteric m lymphnodes lymphatic ly ymphadenopathy+skinhyperpigmentation.Mayhav hesesx,you obstructionmalabsorp ption.(especiallyfat) po olyarthritis,psych/cardiacabnormalities.(butwithth Morphololgy:smallintes stinemucosalsurfaceissh haggywallthick/edemat tous.Villiblunted,foamymsinlaminapropriafille edw/PAS+,diastase w wouldprobablythinkofMA ACorTB) resistantgranules.Lysosomesarestuffedw/partlydigestedrodshapedbacilli.Cancauseenlargedme esentericlymphnodes,thic ckenedcardiac Dx x:PAS+foamymsinthesmallintestinalmucosa valves Rx x:antibioticsw/promptres sponse Dis saccharidase(Lactase)Deficiency Abetalipoproteinemia A Infants:congenitalenzy ymedeficiencyAR,raremutationoflactaseenco odinggene Presentsininfancy(rareinb bornerrorofmetabolism) erprotein (malabsorptionatmilkfeedingexplosive,frothy ywaterystools,abdominaldistention,correct Absorptive A cellsunabletosynthesize s ortransporttrig glyceriderichlipoproteins(AR,raremutationofmicr rosomaltriglyceridetransfe w/milkremoval) MTP). M Cellsareunabletoassembleorexportchylom icrons.Triglyceridesarest toredtheninabsorptivece ells.Appearasfat+cellvacuolesincells. olublevitamin Adultsacquireddeficiency. Alllipoproteinsthatcontain c apolipoproteinBw willbemissing,nochylomic crons,VLDL,LDL.EssentialFAnotabsorpbed.Fatso Wh hy?lactoseisincompletelydigested.Osmoticdiarr rhearesults.Bacteriaferm mentunabsorbed deficiencies,lipidmembranedefects(RBCacan nthocytesspurcells). sug garsleadingtoH2produ uc on(breathtestdetects s).Nohistologicalchanges s. Sx:seenininfancyfailure f tothrive,diarrhea, steatorrhea

Congenital anomalies

Malabsorption Syndromes:
Clinicallysimilar, mayneedbiopsy, effectsarebody wide

Small/LargeIn ntestinePatholog gy CrohnsDisease D

Ove erallEtiology Strongimmuneresponses againstnormalflora(to oomuch Tcellactivationortoolittle controlbyregulatoryT lymphocytes) Defectsinepithelialbarrierfx 15%have1stdegreerelatives affected(9%risk) Butetiologyreallyunkn nown. Linktoimprovedhygienic conditions? Carcinomarisk:highestw/810 yrscolitis,especiallyifhave pancolitis.w/active e (neutrophil)disease,dy ysplasia, primarysclerosingchol langitis. Overall,morecommon nin females,frequentlyons setin earlyteens/20s Where:ANYPARTofalimentarytract, Smallint+rt tcolonsuggestsCD>UC. Lesionsskiparound,involveanus,spar re rectum. Histo:TRANS SMURALlymphocytes, plasmacells, ,lymphoidaggregates. NoncaseatingGranulomas(30%). Cobblestone emucosa.Lumennarrowed d, fibrosingstrictures/obstruction.Sharpl ly demarcatedlesions,fat wrapping/cre eeping. Cause:Idiop pathic.NOD2assoc?(may triggerNFkB).11%pANCA+,ASCA (antisacchar romycescerevisiaeab) Sx:Apthousulcersearly,laterdeep linearulcersthatpenetratewallsand cancausead dhesions,fistulas,sinus tractstoadh herentviscus,outsideskin, blindcavities s.Canhaveperforation, perianalabsc cesses. Tx:Surgeryto t fixadhesions,butnot curativesinc celesionsskip Sx:milddiarrhea,fev ver, abdominalpaininRL LQ. Fluid/electrolyteimb balance+ wtloss/malnutrition n.Anemia (maybebloodlossif fcolon involved) Assocw/SMOKING Complication ns:Canhave uveitis,sacroiliitis, ankylosingsp pondylitis, migratorypolyarthritis, erythemanod dosum, riskGIcarcino oma(56X). Strictures,ob bstruction mayrequireresection r Complica ations:Toxic megacolo on(greatest dilationa atcecum, canbeco ome gangreno ous), developin ngcolon cancerm morelikely thanCD Sx:bloody y,stringymucoid diarrhea,SERIOUSbleeding. LLQpain/ /crampsrelieved w/defecation. Fluid/elec ctrolyteimbalance.

U UlcerativeColitis s
W Where:COLONONLY,spareanus,involve rectum.LesionsCONTINUOUS. Histo:limitedtomucosa,submucosared, ble eeding,granular,friable.Early E crypt ab bscessesexpand,coalesce.Formbroad areasofulceration(canbeextensive e from ch hronicmucosalinflammatio on/damage). Ps seudopolypsarecreatedfromislandsof remainingregeneratingmuc cosa.Ulcers canform,merge,stopatmm m.WallisNOT thick,serosanormal. He ealing/regenerationcanlea adtogland dis stortion,atrophy,submuco osalfibrosis. Dy ysplasiamaydevelopovertime. Ca ause:Idiopathic.75%pANCA+ As ssocw/QUITTINGsmoking Tx x:SURGERYhelpssincelesionsare co ontinuous

Idiopathic Inflammatory BowelDisease

IBS

Rom meCriteria:Recurrentabd dominalpainordiscomfort t3dayspermonthinlast3monthsassociatedw/2+ofthese: Improvesw/defecation n,Onsetassociatedw/chan ngeinstoolfrequency,Ons setassociatedw/changein nformofstool

Isch hemicBowel Dis sease

Vascular Disorders

Sxtha atareredflags Unintendedwtloss,fever r,severechronicdiarrhea/ /constipation,onsetaftera age50,FamilyHxIBD/GIca ancer,celiac disease;PastHxofcolore ectalcancer,RelevantPEfindingssuggestGIdisease,Anemia,elevatedESR,Hig ghTSH No ormalVascularsupply3majorarterialtrunks:Celia acartery,SMA,IMA. Sx:mos stprobablyhaveunderlyin ngcondition Watershed(borderzo ones)atgreatestriskofischemiafromhypoperfusion natsplenicflexure(border r 2phases: thatpredisposesthem SMA+IMA),Rectosigm moidalcolon(borderIMA+pudendal/iliacaa). Initialhypoxic cinjury(vascularcomprom mise).Ischemic erosclerosis; E ElderlyCVproblems,athe Mesentericveinthrom mbosisalsocausesvascular rcompromise. necrosis:nost stainingorcelldetail.Muco osalsloughing, hesion, M Mechanicalocclusionadh Le esions:dependontheinsult: shagginess. h herniation;Hypercoagulablestate; Transmural:fullthickn nessw/suddenacuteocclu usion,majormesentericarteries/veins,serosacan Reperfusioniinjury:bloodflowrestored dtohypoxic ery,shock, T Trauma,procedures,surge becomenecrotictoo(if ( inflammationextends,causes c peritonitis).Arterialsharpdemarcation. tissuecause esthemostinjury.ROS,ne eutrophils, d dehydration,vasoconstrictivedrugs, Venousgradualtran nsition.Necrosisdusky/d dull,rubbery.Hemorrhage(red/purple).Venousonly y inflammatory y mediators,activateHIF1,NFkB,etc.See v vasculitidies(polyarthritisnodosum, n edema.Laterseepu us.Canleadtoacuteabdo omenboardlikerigidity,(SEELECTURETOFILLIN) vascularcong gestion,hemorrhage er H HenochSchonlein,Wegene Mural/mucosalinfarc ctionsacuteorchronichy ypoperfusion.Ischemiaca aninvolveANYlevelofGI g granulomatosis) tractfromstomachtoanus.Patchy,segmental(mostly)orcontinuous.Va ariablethickness Ischemicstricture:v vascularunderperfusion/hyperperfusion. O Onceyouhaveoneevent,youcan involvementwithoutserosal s involvement.Cansee s samesortofchangesas a listedintransmural. Mucosalorsu ubmucosalinflammation,u ulceration a alwaysextendittotransmuralwith Seebloodinthelume en healingw/fibr rosis.Getobstructingstric cture. a anotherepisode Watershedzo onesaremostlikelysites.Clueisprior episodeofblo oodydiarrhea. Ddxw/IBDor infection(microscopicclueisinnearby mucosafew wersmaller/atrophicglands s+fibrosis fromnouri shment,especiallynearth hesurface)

Diverticular Disease

Ang giodysplasia Hemorrhoids Vas scular,nonneoplasticlesion.Malformeddilatedsm mallvenousbloodvesselsandcapillaries.Mostince ecum,rtcolon.Maybe Variciesofan nal/perianalvenoushemorrhoidalplexuses. mu ultiple.Spanmucosasubmucosa.Ectaticnestsofthinwalled,tortuousBV.Coveredbythinnedmuco osa.Tendtobleed Secondarype rsistentvenouspressur restrainingatstoolw/co onstipation,venousstasisof o pregnancy, chr ronic,intermittent;occult,anemia;acute,massivemight m notbedetectableby ycolonoscopy.Inpts>60yo. y portalHTNr rare.Inferior(externalple exus),superior(internalple exus).Rareinpts<30. Pat thogenesis:Mechanicalfac ctors(mmcontractionand dwalldistentiondeepve esselocclusionsuperficialvesseldilation Thinwalled,d dilatedsubmucosalvessels s.Protrudeexposedtotraumaandcanthrombose,ulcerate, recurrentvenousoutflowobs struction),degenerative(m mostlyinpeople>50yr=vessel v weakenedovertime e),congenitalpredispositio on fissure,bleed,,strangulate,infarct (see enw/otheranomalies).Ce ecum(rtcolonhasgreat testdiameter/walltension n,sothiswhereweseemo ostofthese). Div verticula:acquiredoutpouc ching~50%inwesternadults>60yrs.Mucosaonlynomm.MostlyinLcolon(0.51cm).Areasofph hysiologicalwallweakness Mostcases:asx,discoveredincidentally.20% %haveintermittentcramps,discomfort, (wh hereBV,nervespenetratebetweentaeniaecoli).+high h luminalpressure.Exaggeratedperistalsis(mmhypertrophied, h lowfiberdietstoolbulk).See distention,sensatio onofnotemptyingrectum m.Constipation,diarrhea.Minimal out tpouchedmucosaw/fibros sis,NOmuscularis. r.Cancause bloodloss(rarelym massive).Mostwillregress sifearlyindietaryfiber Div verticulitis:initiatedbyobs struction(fecalith)thatmig ghtleadtoperforation.Inflammationextendstoadj jacentmucosa,pericolicfa at,maycausefibrosis, obstructionrequiringsurgery. stri icturedlumen,obstruction n(requiressurgery).Mimic cscarcinoma.Infectioncanleadtoformationofabsc cessorsinustract,peritonitis.

Small/LargeIn ntestinePatholog gy
Her rnias We eakness/defectofperitonealcavitywall,mostly ant teriorlyinguinal/femoralcanals,umbilicus,surgical scars,LigamentofTrietz. Ser rosalinedherniasacprotru udesintothedefect,then visc ceralsegmentsfollow.Sm mallbowel>largebowel> om mentum. Com mplications Incarceration(permanententrapment) entrapmentpressureim mpairsvenoustissue drainagestasis,edematissueswelling. visceralbulkcausespermanenttrapping. Bowelobstruction(obs structivesx) Strangulation(compro omiseofmesentericaa supplyandvenousdrai inage).Mayleadto infarction Adhesions(#1in nUS) Fibrousbandsbe etweenareasof inflammation(fr romprior surgery,endome etriosis, infection).From mbowelto bowel,bowelto owall.Bowel loopscanslidethroughand becomestrangulated
Directherniamedialtoinferiorepigastricvesselswhen w abdominalcontentsgo othroughexternalinguinalring g. Adultonset,entersthr roughHesselbachtriangle(wea ak pointinabdominalwallfascia) Indirecthernialatera altoinferiorepigastricvesselswhen w abdominalcontentsgo othroughdeepinguinalring.Covered C byinternalspermaticfascia, f congenitalonset

Intestinal Obstruction
Sxvomiting, constipation,abd pain/distension

Intuss susception Intest tinalsegmenttelescopesintoimmediatelydistal segme ent.Mesentericvasculars supplypulledalongand canle eadtoinfarction. Infant tsnoanatomicdefectp pointoftractionmight beinf flammation.Mayreducew w/bariumenema Adults spointoftractionismas ss/tumortxissurgery

Volvulus Completetwistingofbow welloop arounditsmesentericvas scular attachmentbase.Leadstoobstruction andinfarction. Adultsoccursinsigmoid dcolon Childrenassocw/malro otaionseen insmallintestine

Polyps:
epithelialmasses thatprotrude fromthemucosa

Nonneoplastic(NOmalignan ntpotential)abnormalmaturation, m architecture Hamartomouspolyps:focalmalformationsoflaminapropriaandglands.Donthavemalignantpot tentialontheirown(but riskifseenw/adenomas s) Hyp perplasticpolyps:usuallyfound f incidentally,atolder r In nflammatory Juvenilepolyp: Hamartomasmay age e.Grosssmallmucosalprotrusions. p Multipleor polyps: 13cm,pt<5yo.Rou und,smooth, beinman nyorgans riskofcarcinoma(GI,pancreas,breast,lung, sing gle(<0.5cm).Microscopic cabnormalmaturation. PuetzJeghe ersPolyp: Ly ymphoid lobulated,stalked.Cystically (GI,muco ocut). gonads,urinogenital).Int testinalhamartonas+ Del layedsheddingofmaturecells. c Accumulationofold, , arborizingnetwork n ofglands, Cronkhite (n normalvariant dilatedglands.Nomalig m riskofcarcinoma adenomas can lead to ade enocarcinoma. not tneocells.Nomalignantpotential. p Leadstocell laminaprop pria,smoothmm,CT. Canada: bumps potential. (breast,follicular f cro owding,infoldinginmaturesurfaceglands.Ddx Ifmultiple,alwaysasyndrome. GIhamartomas, in ntramucosal Single sporad dic cases. thyroid, w/s sessileserratedadenomas(dontwanttomissthese). Occurthrou ughoutGItract. ectodermal ly ymphoid 80%inrectumpresent endomet trial) Wh hiteglandsonsurfaceONLY Y. Alwaysinsm mallintestine.Riskof abnormalities, nodules) w/bleedingretention intussuscep ptions.Maybein nocancerrisk polyps. stomachan ndcolon.Pigment (anotherpolyp Multiplepart tofjuvenile seenmucoc cutaneously syndrome) polyposissyndrome (periorificia alskin,buccalmucosa, Rectal/colonhamartomas+ palmsofha ands,genitalskin). adenomasmay yleadto adenocarcinom ma. Neo oplastic(precursorstocar rcinoma).Newcellproliferationanddysplasia. Villousadenom ma:large(10cm),sessile e,shaggiersurface,13cmabove Ma alignantpotential:dependsonsize: Adenomatouspolyp: ntmembrane adjacentmucosa.Intramucosalcarcinom ma:glandsbreachbasemen <1cmrisk,>4cm risk. DARKglands swithtoomanynucleion butdontinvad demmucosae Highgradedysplasiaof ftenfoundinvillous surface.Epithelialneoplasms. Ex:Sessi ileserratedadenoma:whi itemucincontainingglandsfromdeep (shaggy)areas. Gland,cellproliferation p w/dysplasia. cryptsto osurface,NOnuclearchanges.Lookslikelargehyperplasticpolyp. Anyadenomatouspoly yprequiresCOMPLETE Precursorstoinvasive yHNPCCofrt Associatedw/mismatchrepairmut tationintumors(especially removalpotentiallyharbor h carcinoma! adenocarcinoma. colon) o Pedunculatedpolypectomymightbe pedun nculated(w/stalk)or adequate.Decidetoresectfurther sessile e(nostalkvelvety Adenoma:Sx:asx(usua ally). dependingonsta alkinvasion,blood surfac celooksraspberrylike). Mayhaveanemia,occu ult vesselinvolveme ent,andinvasionnear Tubula aradenoma:small, bleeding.Largevillous polyps resectionmargin n. pedun nculated,smoothsurface Surveillanceiskeytodet tect maycauserectalbleed ing, o Sessileglandsinvade i submucosano Villou s large, shaggy surface, beforemalignanttransfo ormation! mucushypersecretion stalktoactasbu uffer.Polypectomy sessile e w/protein/K+loss. mightnotbeeno ough. Attenu uated FAP: <100 FAP(FamilialAdenom matous Inrightcollon, polyps.Presentslaterinlife Polyposis) HNPCC(HereditaryNonpo olyposis mucinous/ /signetringcell (50yo) ),50%cancer. Adenomatouspolypos siscoli(APC ColorectalCancer) type,poor rlydifferentiated. MUTYH Hgenemutationin gene)mutation. riskcolorectal+extraintes nal Tumorlym mphocyte <10%.DNAmismatch 1002500polyps.Anytypeof carcinomas.NopolyposisBUThave Oth herthingsthatGiveElevate edRiskofColonCancer infiltrates. adenomatypicalad denocarcinoma. repair.Mayhavesessile polypsofanytype.Carcin nomasat Juvenilepolyposis(pres sent<5yo) edadenomas Colon,otherGitractsi ites.Presentsin serrate earlieragethansporadictumors Fam milialSyndromes PeutzJegher(present~ ~15yo) MULTIPLE coloncancers mucino ousadenocarcinoma. teens,100%progresstocancerby (throughmicrosatelliteins stability 30.Prophylacticcolec ctomy. pathwayfrommutationsinDNA Turcotsyndrom me(CNS MISMATCHREPAIRGENES S) tumors), Precursorlesion=se essile Gardnersyndro ome(bone, seratedadenomas,presents desmoidstumor rs,dental <40yo. abnormalities)

Small/LargeIn ntestinePatholog gy
#1malignancyisadenocarcinoma a.Mostcolorectalcancers sdevelopsporadically. Mostarise a inpolyps.Peakage60 6 80.Youngeragethink kulcerativecolitisor syndrome. Risk: w/fiber,refinedCH HO/fat,transittime,antioxidantactivity, bilesaltcontact.w/ASA,NSAIDSbyinhibitingCOX2neededforPGE2that promotescellproliferationafterinjury,coloncancerrisk k.COX2inhibitorusedas FAPpro ophylaxis! Gross:mostaresingle,maydirec ctlyextendtoadjacentstru uctures(lymphnodes,liver r, lungs,bones, b brain). Proximal, P rtcolon(oftenexophytic,bulky.Tendnottocauseobstructionsee e fatigue, f weakness,irondef ficiencyanemia); Distal, D left(napkinringencircle, e constrictulcerated,infiltrativetendto cause c obstructionbleedingmelena,bowelhabitch hanges) Prognosis: P dependsondep pthofinvasion.Worseifin nmuscularispropria. Lymph L nodeinvolvementalso a worse.Intestines/colo ondrainviaportalveinto liver.Distalrectumandan nusareNOTdrainedviaportalcirculation. Samehistology h generallywhethe errtorleftcolon.Welldifferentiatedglandsto undiffe erentiatedpossible.Mucin ninglands,cells.Intheinterstium(aidstumor dissect tionthroughwall).Invasioncausesastrongdesmopl lasticstromalreactionthat t causeshardnessofthewall Pathogenesis: APC/Bcatenin npathway:localizedepithe elialproliferation smalladenoma asinvasivecancers.Du uetolossofAPC gene(tumorsu uppressorgene,gatekeepe erforBcatenin mutationsofAPC A in80%ofsporadicca) o KRASmost m frequentlyactivated oncogenein adenom matous/colonca.Mutated in<10%adenomas <1cmsiz ze,in~50%adenomas>1c cm,~50%of carcenomas. o Tumorsuppressors: s SMAD:lacko ofSMAD4GI tumors,SMAD2,APC,p53(in708 80%ofcoloncancers sugges stedlateincoloncarcinoge enesis) o Telomer rase:stabilizeschromosom meactivityin colonca a. Microsatelliteinstabilitypathway:Gene eticlesionsinDNA mismatchrepa airgenes.Doesnthavecle earlyidentifiable morphologicco orrelates.MSH2,MLHSDN NAmismatchrepair genesallowhig ghmutationrates.TGFB,, BAXtumor suppressorsinactivated.BRAFoncogene eactivated. Generallyslowprogressing,screeningshouldp preventmostcases!!! St tagingofColorectalCance er

Col lorectal Ade enocarcinoma

AnalCanalCarcinom ma Carcinomasresemblenativeepithelium/mixtu ures: Upper:Normallyhascolumnarglandular rectalepithelium.GetsADENOCARCINOMA Middle:Norma allyhastransitionalepithe elium.GetsPureBASALOID D(frombasaltransitionalc celllayer) Lower:Normallyhasstratifiedsquamous sepithelium.GetsSQUAM MOUSCELLCARCINOMA.P PureisHPVrelated(w/condyloma accuminatapre ecursorsowartsfirst)

Tumors

Car rcinoidtumors Neu uroendocrinetumorsarisefrommucosalendocrine ecells.Resemblecarcinom masbutmayshowlessagg gressivebehavior. Pre edominantsiteGItract/lu ung.MostcommonGIsite esappendixandsmallint testine.GIcolon,rectum m,pancreas, stomach,biliarytree,liver.Se ecretebioactivesubstance es,maycausecarcinoidsyn ndrome.Appearspaleyellow.Difficultto pre edictmalignantbehavior.Depend D onsiteoforigin(ra arelymetastasizefromapp pendix,rectum,usuallydofromsmall inte estine).Aggressivegrowth hhighdepthofpenetration;especiallybeyondmus scularispropria. Gross:Solitary(inappe endix,colon,rectum),mult ticentre(insmallintestine,stomach).Muralorsubm mucosal,haveintact overlyingmucosa.Cutsurfaceissolid,yellow.In nvasioncauseswallfirmnes ss,smallbowelkinking(causingobstruction). <2cmsizeinmostsize,tendtobelarger(3cm)in ncolon. Microscopy:neurosecr retorygranules(densecore e).Monotonouscellsinne ests,islands,trabeculae,ac cini.Nucleiare uniform,blandround/oval,w/stippledchrom matin.Scant,amphophiliccytoplasm. c Seedensecore egranulesonEM. StainschromograninA, A synaptophysin,neuronspecific s enolase Clinicallyasx.Maybe esxifkinkedsmallintestin ne(bowelobstruction),pain/wtloss/bleeding(espla argecarcinoidsof colon),carcinoidsyndro ome(<10%casesduetopresenceofactivesecretory yproductsinsystemicbloo od))5HT, histamine,bradykinin,kallikrinin.Willbeabletodetecthigh5HIAAinurin ne(becauseithasbeendeg gradedtothis metabolitebytheliver)However,ifintheRECTU UM,theydontusuallysecr rete5HT(sourinary5HIAA Awillbelow) Syndromefeaturesarerelatedto5HTdeliveredto t systemicbloodsignofmetastasisbecauseitavoidsinactivationin theliver.GIlocalizedtumorsshouldnthavethes sesx.Seeblood/urine5HT.Skinflushing,bronchoconstriction, cramping,D/N/V,Right tsidedvalvularheartdisea ase(causesdeathin50% endocardialfibrosis). Bestprognosisinnon nmetastatictumorsofapp pendix,rectum.Deathdue etowidespreaddisease,liv verfailure,carcinoid heartdisease,bowelob bstruction/perforation,ble eeding

Ga astrointestinalLymphoma a ,enteropathy IntestinalTcelllym mphoma:Spruelikeillness, associated.Arisesinsmallintestineadults30 3 40yrs,Hx ognosispoor ofmalabsorptionsy yndromefor1020yrs.Pro (11%5yrsurvival). sbutmost MALTlymphoma:c canariseinPeyerspatches ch.Different ariseinareasw/out tmaleinducedinstomac searly, fromnodallymphom masactlikefocaltumors ct.ExpressB resectable.Relapse ecanbeconfinedtoGItrac cellmarkers(CD19,20)butNOTthose(CD5,10) 1 expressed st innodallymphomas s.Chemotxmaybecome1 tx. ypical o Earlylesion:lyphoepitheliallesionaty lymphocytesinfiltratemucosa.Glandsareeffacedor destroyed.Ly ymphoidtissueexpands.Monoclonality M indicatesmalignancy.

GItractisMOSTCOMMON SITEofextranodal ly ymphomas. Lymphomamorpholo ogy:variablediffuse mucosal/muralinfilat trationw/thickening.Can n havepolypoidprotrud dinglesion,fungating ulceratedmass,disse minatedserosalnodules. Sx:canhaveobstruct tion,perforation.Can destroymmpropriaa andcausemotilityproblem ms (therebycausingseco ondaryobstruction).Duet to lackofstromalsuppo ort,largetumorsmay perforate(especially afterchemotumorbul lk) Bcell(95%) o mostcommon areMALTlymphomas#1 1 siteisstomach..Manya/wchronicHpylo ori gastritiscured dbyantibiotics.Othersa/ /w cytogenetictra nslocations.Bothactivate e NFkB(Bcell survival/prolifera on) nd o 2 mostcomm monDiffuseLargeBcell lymphoma(EBV V+)immunodeficiency associated:tran nsplantpts,HIV,Burkitts lymphoma(Afr rican/endemic,sporadic, HIV)

ytes Laterlesion: mixofmalignantlymphocy expands,repl laces,destroyslargeareasoftissue.

SmallIntestine Tum mors Uncommon U tumorsite,mo ostlybenign. o Epithelial:Adenomas(25%)AmpullaofVater r(3060yo,similarto colonicadenomas);Hamartomatouspolyps;In nflammatory,lymphoid polyps. o Mesenchymal:GIST(gastrointestinalstromaltumorsbenignor malignantbehavior);lipomas;neuromatoustu umors;angiomas Malignant: o Adenocarcinomamostlyinduoden num.Age4070.Encirclin ngorexophytictumors.Ob bstructingsxcramping,N/V, N wtloss. Jaundice(ampullary ( tumors),occult tbloodloss.Pointoftracti ionforbowel(canrarelycauseintussusceptions).Most M are FAP,HNPCC, sporadicw/no w predisposingconditio ons.Riskw/chronicinflam mmation(Crohns,Celiac).L Lesscommonlyinherited(F PeutzJegher) o Carcinoidtumors;lymphomas;sarco omas

Appendix
Normal N
67cmlength,anchoredbymesentericexte ensionfromileum.Nokn nownfx.Richlymphoidtis ssueinmucosa/submucos sa(formsgerminalfollicles s,lymphoidpulpinyoungpeople). Progressiveatrop phyovertime. Mostcommonacuteabdominalsurgicalcondition Psoassign:e extendingrightlegathipm makespsoasmmcontractorhavingptraisingthighagainst a your 5080%due etoobstruction(fecalith).Canalsobeduetogallstone, handifthiismovementispainful,ind dicatesappendicitis tumor,ballofworms.Suppurativeinf flammation,edema. Rovsingssig gn:paininRLQwhenpressdowninLLQifappendicitis Ptisteen/youngadult,anyage,M>F.Lifetimerisk7%. Obturators sign:Rhypogastricpainwh henlegrotatedinternallya athipifappendixisinflame ed Morphologytheprogression: Cutaneoush hyperesthesia:localizedpa aininall/partofRLQonth heskinofthearea o Early yacuteappendicitis:dull,granular g redmembrane Thing gsthatmimicit: fibrin nopurulentreactionoverse erosa o Mesentericlymphadenitissecondarytoenterocolit tiscausedbyYersiniaoravirus v o Acute esuppurativeappendicitis s:abscessformswithinthe ewall, o Systemicviralinfection,a acutesalpingitis,ectopicpr regnancy,mittelschmerz,cystic c fibrosis, ulcerations,fociofsuppurativenecrosisinthemucosa Meckeldiverticulitis. o Acute egangrenousappendicitis s:largeareasofhemorrhag gicgreen Dx:m mustfindneutrophilsinmuscularispropriatodxacuteappendicitis.(butcanalsoseethis ulcerationofmucosa,greenbla ackgangrenousnecrosisth hrough w/alim mentarytractinfections soevidenceofmuscularwa allinflammationneededfo ordx).20 thewall w serosa.Leadstorup pture,suppurativeperiton nitis. 25%F FPdxestimatedbutthou ughtthatdiscomfortofexp ploratorysurgeryisworththe t 2% Sx:Periumb bilicalpaintoRLQ.N/V, ,abdominaltenderness.Mild M fever, morbiidity/mortalityassociatedw/perforationandcomplicationsthrombosisofpo ortalvenous WBCelevat tedto5,00020,000. draina age,liverabscess,bacteremia. Carcinoidtu umor(mostcommon),usu uallydiscoveredincidentallyduringsurgery/whenexa aminingresectedappendix x.Indistaltip(23cm bulbousswelling). Adenocarcinoid(gobletcell):typicalcarcinoid c patternw/mucinvacuolecontainingcells. Mucocele:dilated d appendixfilledw/m mucin.Canbecausedbymucinous m adenocarcinoma a Pseudomyx xomaPeritonei:abdomenisfilledw/semisolidmucin nfromcontinuedcellularp proliferation/mucinsecreti ionfrommucocele.Can holdinchec ckw/debulkingprocedure esbuteventuallyislikelyfatal. Generallyfromruptureoffiscusorerosion e throughaviscus.Causes C appendicitis,rupt turedpepticulcer,cholecy ystitis,diverticulitis,strangu ulatedbowel,acutesalpingitis, abdomina altrauma,peritonealdialys sis. Organisms s:justaboutanythingEcoli, c a/bhemolyticstrep,St taphaureus,enterococci, G,Clostridiumperfringen ns.Cangetgonococcus/Ch hlamydiafromgynecologicinfections Morpholo ogy: 24hourspostinitiation,perit tonealsurfacelosesitsgra ay/glisteningquality.Accum mulateserous/turbidfluid d. Late er>creamy/suppurativefluid, f maybecomethick,plastic,inspissated May yhealspontaneouslyorw/ /tx:Possibleresults: o Exudatesresolvesw/no ofibrosis, o Residualwalledoffabsc cessespersistandmaybefociforfutureinfection, o Exudatesmayorganizeandformadhesions) Fibrousov vergrowthofretroperitone ealtissues,mayinvolvethe emesentery.Causeobscu ure(mayberelatedtometh hysergideergotderivativeformigraine,surgeryhx,radiationtx). Possiblyautoimmune/systemicorigin. Sortofananalogofdesmoidtumor. . wing Cancomefromlymphaticchannels,pinchedoffentericdiverticulaoffdevelopingforegu ut/hindgut,fromurogenita alridge/derivatives,fromw walledoffinfections/follow pancreatit tis,malignantorigin.Canseem s tobeabdominalmas ssesandcausedxconfusio on

Acute A Appendicitis

Tumors T

Peritoneum
Inflammation:P Peritonitismaybefromba acterial
invasionorchemicalirritation. Mostcommon: o sterileper ritonitis(leakedbile/pancr reatic enzymes), o Perforated/rupturedbiliarysystem(usually w/bacteri ialsuperinfection), o Acutehem morrhagicpancreatitis(freefat, chalkywh hiteprecipitates,bacteria permeatin ngbowelwall), o Surgery(f foreignmatterleadtoreac ctions), o Gynecolog gicalconditions(endometr riosis, ruptureddermoidcysts) Tumors PeritonealIn nfection

Sclerosing Retroperiton nitis MesentericCysts C

Virtu uallyallmalignant Primary:Rare o Mesotheliomas:from f mesothelium.Verypoorprognosis.Associatedw/asbestosexposurein80%.Oftenneedimmunoh histochemicalstainstodiffe ferentiatefromadenocarci inoma o Desmoplasticsma allroundcelltumor:rare,fromperitoneum.Unknow wnpathogenesis.Mayberelated r toEwingsarcoma,rhabdoidmyosarcoma,pr rimitiveneuroectodermalt tumor.T(11;22),(p13;q12) )translocationEWSWT1fusion Secondary:prettycomm moncanhavemetastaticseeding,penetrationintoserosalmembrane

Liver/BiliaryTract
Surgica alfunctionalorganization: :8segmentscaudatelob beissegmentI,therestmo ovefromLRacrosstheli iver(eachhasindependen ntvascular/biliarypedicle,venous v drainag ge).Bloodsupply:25%of fCOviaportalveinandhepaticarteryviahilum.Wt t:14001600gm BasicMicroscopic M Morphologyof o theLiver: Hepatocyte: H bathedinsinu usoidalblood(mixtureofportal p andarterialblood),d drainsthroughfenestrationsinhepaticveins.Canm make~500biochemicalrxns s,can synthesize s 150proteins! Bile B System:BilecanalliculiCanalsofHerringBile B Ducts(intraandextrah hepatic) Space S ofDisse:containsfa atcontaining/VitArichstellatecells.Plasmaderived d,drainsintothelymphatic csystem. Kupffer K cell:partofRESsy ystem,onendothelialcellside. s Liver L acini:Zone1(nearpo ortaltriad)=bestbloodsup pply,Zone3(nearhepatic vein) Normally N theliversurface appearsamahoganybrow wn Norma alLiverFunctions Uses, U supplies,storesalot t: o Energymetabolism: :Glucoseconsumption(gly ycolysis)production(GNG) )/Bloodsugarcontrol;Glyc cogensynthesis,FAsynthesis:energystorage;FAoxidation,TCA cycle,ATPProductio on o Substrateinterconversion,clearance:Bilirubin nconjugation,clearance;C Cholesterolsynthesis,TGsynthesis;ExportVLDL,preHDL;uptakechylomicronremnants, r LDL, HDL;BileAcidSynthesis:solubilizationandupt takeoffat/fatsolublevitam mins;Aminoacidsynthesis s,interconversion,deamin nation,ammoniafixation;Drug, D toxin detoxification,andclearance; c Damagedcells,bacteria, b clearance o Proteinsynthesis(90%ofallplasmaproteinsinbody):Albumin,clotting gfactors,bindingproteins s,aLP Liverzo ones Periportal: P aroundthepor rtaltriad(1)highlyoxygenatedbloodflowsfromhe epaticartery/portalvein,travelstocentralvein. Sinusoids: S (2)midzonal Vein/central: V aroundcentr ralvein(3)willbeatriskofinjuryviatoxins,mo ostproblemsfromlowerpe erfusionofblood Disorganization D ofthissyst temwillimpairfxofliver

LiverFunctionTests(t thetrueonesarebilirubin,PTT,Albumin,Ammoniathesearedirectlymeasur ringthefunctionofthelive er) Aminotransferases: AlkalinePhos sphatase: GammaGlutamyl Albuminisan Prothrom mbintime Ammonia: metabolized AST(SGOT)inm manyorgans,synthesizedin nhepatocytecytosoland inman nytissues,especiallybone,liverAPfromcanalicular Transpeptidase(GG GTP): indicatorofliverfx(~ allcoag gulation byliverhigh h insevere es,cirrhosis), mitochondria membr rane,bileductepithelium. occursinmanytissu ues(BUT 10g/dayis factorsm madeby dysfx(Reye ALT(SGPT)ismo orespecifictoliver,synthe esizedincytosolonly Hallma arkdisproportionate(toAS ST/ALT)APriseincholestas sis NOTINBONE).Indu ucibleby synthesizedand liver,exc ceptfactor portalsystemic reecthepatocyteinjury/leakage,poorcorrelationw/histologicaldamageor duetosecre on,notreten on n.Riselagsa eracute ETOHandotherdru ugs,mayrise secreted,w/T=20 8.Goodindicator shunting prognosis obstruction,sincemustbesynthe esized,falllagsafterrelief 2.5Xupperlimitofn normal>AP. days. formoni itoring 50100Xupperlimitofnormalinacutehepatitis,especiallyinfulmin nant ofobst tructionsinceT=1wk.AP A cannotdifferentiate Usedtoassessacute eETOH Hypoalbu uminemiaalso acuteliverfailure BUNincirrhosis c hepatitis,ischem mia,acutebileductobstruc ction betwee enintrahepaticandextrah hepaticcholestasis.Maybe e intake(butnotvery y reliable). fromextr rahepatic becauseofshort eflectshepatic 25Xupperlimit tofnormalinETOHliverdi iseaseandmostotherchro onicliver highw/normalbilirubin(focalles sionsgranulomata, Cholestasisstrongly y suggestedif factors(lo owintake T. Bilirubinre diseases tumors s),Morereflectsbilirubinexcretion e thanAPsynthesis s. APandGGTPareele evated.As and/or lossrenal, clearance/excretion UsuallyAST/ALT T<1;inETOHhepatitisofte en>2;pyridoxine,oftendeficientin Cholestasislikelyifnormalamino otransferases.AP23X withAP,cannotdiffe ferentiate gut). also. alcoholism,isco ofactorforboth,ASThashigher h affinityforitthanALT,thus upperlimitofnormal+highamin notransferasesisnon intrafromextrahepa atic ALT=ra o specific c. cholestasis. Test Resultw/hepatocell lularinjury Resultw/cholestasis s/infiltration Constructionalapraxia:lo ossofspatialplanning(cloc ckdrawingabnormality) canindicatemildencepha alopathy Bilirubin 130XULN 130XULN Lactuloseusedw/elevat tedprotein ALT/AST 5100XULN 15XULN AP/GGTP 110XULN 130XULN MELD(ModelforEndSta ageLiverDisease) Albumin insubacute/chronic Usuallynormal o Predictsmort talityin3monthsbasedon nserumbilirubin,creatinin ne,PT(INR).ascorefrom m040where40indicatesthe t ptwill Prothrombintime inseveredisease,nofallaftervitK Oftenhigh,correcte edafterparenteralVit certainlydie,102027%willdie,and d<10indicatesonly4%will). supplementation K cationrate) o Alsopredictsoperativerisk(MELD>8in ndicatesatleast44%comp plicationrate;MELD<8ind dicates10%orlesscomplic UltrasoundorCTsca an Normalbiliarytractifextrahepaticobstructio on Dilatedbileducts o MayreplaceChildsclassification. ERCP Normal Dilatedductsifextrahepaticobstruction ImportantinDx: o GGTP,alkalin nephosphatasewithoutot therabnormalitiespointto omorefocalproblem PtHx:Modeofonset,knownliverdisease,assoc ciatedsx/diseases,exposur rehx(travel,alcoholintake einUSblood o Enzymeeleva ationsthemselvesarentgo oodatpredictinghowseve ereliverproblemsare/will lbecome transfusionbefore199 92HepC,sharedneedles s/bodyfluids),drugs(dietarysupplements),recent upperGIsurgery,GI o Nogoodtestbeyondbiopsytotellcirrh hosisvsnoncirrhoticconditions,noreliableimaging bleed(hematemesis,m melenaesophagealvarice esseenw/cirrhosis).

Liver/BiliaryTract
Deg generationandIntracellul laraccumulation Necrosis sandapoptosis:Canbedu uetoanysignificantinsult. Fibrosis(Cirrhosis):Respo onsetoinflammationordi irecttoxicinsult.Generally yirreversible, Hepatocytesswellfrom mtoxicorimmunologicacc cumulation Zo onaldistribution:Ischemicanddrugscausecentrilob bular,Eclampsiacauses butrecentevidenceindic catessometimesreversible e.Subdividesliverintonod dulesof Triglyceridefatdroplet tsmayaccumulateinhepatocytes ce entrilobularandmidzonal,Butmostinjuriesareacros ssallzones(periportal, proliferatinghepatocytes ssurroundedbyscartissue e.DeathofhepatocytesECM Patternsof (Steatosis)canbemic crovascular(asseeninpre egnancy,fatty midzonal,centrilobular) deposition,vascularreorg ganizationtothedetrimen ntofreperfusionofhepatocytes Injury liver,valproicacidtoxic city)ormacrovascular(NAFLDnon Inflammation:Influxofacut teorchronicinflammatory ycells(Hepatitisex Collagenisdepositedinto ospaceofDisselosefen nestrations,shuntingthrou ughscar alcoholicfattyliverdise easeincreasinglycommonmetabolic ge enerallycauseselevateden nzymes) venouspressure.Thisisa allduetoactivationofstel llatecells(becomemyofibr roblasts, syndrome) Re egeneration:Aslongasstr ructuralarchitecturestaysintact,generallyis Kupffercellshelpmaketh hishappenbyreleasingchemokineslikePDGF,TNF). Copperorironmayacc cumulateinhepatocytes co ompleteevenwithmassive eresectionornecrosis Cau uses:after8090%lossofcapacity. c Concurrentstres ssmayprecipitatefailure(G GIbleeding,systemicinfec ction,heart Clinicalfeat tures:lowalbuminemia,lo owclottingfactors(coagulopathy).bilirubinemia(jaundice)+ammonemia+ failure,majorsurgery) estrogenem mia+portalbloodshun ng(varices/bleeding,feto orhepa cus).Pa entsareatriskofotherorgansystemfailure Causesofacuteliverfa ailure: (Generallythere t arefewmorphologic ctissueabnormalitiesinth heseorgans) o Massivenecrosis s:Drugs/toxins(38%acetaminopheninUS,Carbonte etrachloride,mushrooms,Hepatitis Disturbancesinconsciousness( (encephalopathy)CNS/neuromuscularsystems ammonia,possiblyedem macanrange A/B) frommildconfusiontocoma,a asterixis o Noovertnecrosi ishepatocytedysfxw/no onnecroticcells:Reyessyn ndrome,fattyliverofpregn nancy, Renalfailure(hepatorenalsynd drome)kidneyshaveo outputBUNandCrea atinine,hyperosmolarw/lo owNa+.Rapid HepaticFailure tetracycline onset toflowurineoutput.Poo orprognosisw/thisonset(2 2wksifrapidonset,6wks sifinsidiousonset) CausesofChronicLiverfailure:Progressivechron nicliverdisease(mostcom mmoncauseofliverfailure)via Respi iratoryfailure(hepatopulm monarysyndrome)lungshavehypoxemia+intrapu ulmonaryvasculardilatatio onmostlydue cirrhosis(alcohol60% %,hepatitis10%,biliary10%,cryptogenic15%). toventilationperfusionmismat tch. o PEsignsjaundic ce(maynotseeuntilbilirubin>3mg/dL,maymissw/out w UVlightsource),spider Jaund dice,hypoalbuminemia(as scites,edema),hypoglycem mia,portalHTN(ascites,sp plenomegaly,caputmedusa, telangiectasis,pa almarerythema(duetoloc calvasodilation),whitenails,gynecomastia,atrophic ctestes, hemo orrhoids),coagulopathiesf fromclottingfactorproduction hepatomegaly(m maybeabsentincirrhosis) Fetor rhepaticusbodyodorth hatismusty/sweet/sourdu uetomercaptanformation nviabacterialactiononGImethionine Diff fuseprogressivechangesbridgingfibrosis(scarring g),Parenchymal Hepatocytedeathstimulatesnodularregene erationofsurviving nod dules(regeneration),architectural(BV)reorganizatio on hepatocytes(macr ronodulesseveralcmormicronodules m <3mm) Cau uses:alcoholabuse,nonalcoholicfattyliverdisease, ,viralhepatitis,biliary Reorganizationofentirevasculararchitectureofliver:collagen(typeII, dise eases,hemochromatosis/h hemosiderosis II)depositedinspa aceofDisse,formsconnect tingfibrousseptaethat Pat thogenesis: distortsthelobule. .Centralveinportaltra acts,portalportaltract. Cirrhosis Stellatecellactivationcausesprogressivefibrosiscellproliferation, Bloodshuntedaro oundparenchymaunder rperfusion.Obliterationof f reallyextracellularmatrix m secretion,reallycollagen c synthesis. portalareabiliarychannels c jaundice.Sinu usoidalendothelialcell Phenotypechangesli ipocytetomyofibroblastw/contractile w fenestrationsarelo ostalso(SpaceofDissebecomesacapillarylike properties;vascularresistanceportalHTNduetocytokines channelnosolute eexchangesbetweencells sandplasma,secretion of producedbymanydifferentcells:Kupffer,inflam mmatory,epithelial, albumin,clottingfa actorscellfxlabssho owalbuminand hepatic,bileductalso oECMdisruption,directto oxineffect prothrombintime) ) PortalHypertension Cholesta asis Impairedbilesecretionbycells(dysf sfx)orflowthroughbilechannels(obstruction). Extrahepatic(usuallysurgica alsolution):stonesinbileduct,tumorswithin/comp pressingbileduct Causes:resistancet tobloodowthroughtheportalvein: Intr rahepatic(usuallynotsur rgicalsolution):alcoholicliverdisease,primarybiliar rycirrhosis,viralhepatitis,meds Prehepatic:por rtalveinthrombosis,massi ivesplenomegaly Results: Posthepatic:rig ghtsidedCHF,constrictivepericarditis,hepaticveinobstruction o Live ercellinjury(alkalineph hosphataseandGGTP) o Intrahepa atic:cirrhosis(mostcases),severediffuse(fattyliver,schistosomiasis,sarcoido osis) Bilir rubinaccumulationinseru um(totalbilirubin),jaun ndice,icterus o Incirrhos sisresistancetoportalbloodflowinsinusoids;more m bloodflowintoporta al Pruritis(possiblyfrombileaciidsinskin) venoussy ystemfromeffectofhepaticfailureonsplanchnicart teries(dilatedduetoaction nofNO) Cho olesteroldepositioninskin n,tendons(xanthomas) o Complicat tions:Ascites(accumulatio onofserousperitonealflui id),portosystemicshunts Fatmalabsorption(Lowabsor rptionofADEK) (esophage ealvarices,bleeding),cong gestivesplenomegaly(hype ersplenism,cytopenias),he epatic Mo orphology:Whetherobstru uctiveornonobstructive,bilepigmentaccumulatesinparenchyma.Dropletsin encephalo opathy(bloodammonia a) hep patocytesappearfeathery y.Bileplugsincanalicularspaces.Kupffercells,apo optoticcells Sx:splenomegaly,ascites,caputmedusa,hemorrhoids,pedaledema a sregenerate Inobstructive, o bileductdisten ntion+reactivechangeinportaltractsductularproliferation(reactioncells asduct d cellsandhelptodetox xsomeofthebreakdownproductsofbileinthespaces)edema,neutrophils BileSaltsandabso orption: Cholicacid,chenodeoxycholicacidact a ashighlyeffective detergentstosolubizelipidsingutlum menandsolubilizingwater r insolublelip pidsfromhepatocytesinto obile 1020%dec conjugatedinintestineviabacteria,butfecallossis matchedby ydenovosynthesis(0.5g/d day). Fecallossofsterolsinbilesaltsandre esidualfreecholesterolisthe t onlyeffectiv vewayforeliminationofexcess e cholesterolfromthe e body 95%reabso orbedinileum,returnedvia aportalbloodandreused.

Causesoflowbile e Hepatobiliarydisease(secretion),Precipitated P bileacidsinLO OW pH,bacteria alovergrowth(deconjugateacids),malabsorption(ile eal disease)

Liver/BiliaryTract
BilirubinMetabolism: Inmacrophages s(spleen):Heme(Hemeoxygenase)biliverdin(b biliverdinreductase) bilirubin(UCB) Blood:lipidsolu uble,hydrophobicUCBtrav velsinbloodattachedinalbumin.Cannotbe excretedinurine e Hepatocytestak keupUCB,conjugateUCB+glucuronideviaUDPGTinSERCB(water soluble) Canaliculi:CBisexcretedintocanaliculivia aorganicaniontransporte er(MRP2)inbilevia biliarytractinto ogut Gut:Intestinalb bacteriadeconjugateCBcolorlessurobilinogenurobilin(orange), o MostUBp passedinfeces. o ~20%rea absorbed,90%ofthisremo ovedbyliverandreexcretedinbile,remainder passedinurine Normally,>80%serumbilirubinisunconju ugated o HighUCBtotalbilirubinrarely>5mg/dL m (normalliverfx),neonataljaundice commone estcauseofelevatedUCB o GilbertsD Disease(AD?)ismostcommonadulttypeofUCB(~5 5%),mostlyreduced UDPGTac ctivity.M>F,onsetinteens s,w/stressorfas ng,be enigncourse o CriglerNa ajjarTypeI(AR):geneticla ackofUGT1A1,Fatalwitho outtransplant o CriglerNa ajjarTypeII(AD):Nonfatal,reducedactivityofUGT1 1A1reallyyellowskin butPheno obarbitaltxcanimprovebi ilirubinglucuronidation(hy ypertrophies hepatocellularER) o DubinJoh hnson(AR):hereditarydef fectinMRP2canalicularpr roteinthattransports bilirubing glucuronides,relatedorgan nicanionsintobile.Darkly ypigmentedliver. o Rotor(AR R):asxhyperCB,livernotpigmented.Jaundicew/nosx. Normal(nojaundice): Blood:CB<20%,liverenzymes normal(AST,ALT,ALP,GGT) Stool:Normal(hasUBG G) Urine:HasUBG,NOCB B(never anormalfindinginurin ne becausedoesnthavecontact c w/bloodinitsmetabolism) Prehepaticjau undice:overproductionof bilirubinand/o orliveruptake.(Causes s Extravascularhemolyticanemiaothercauses w/outurine eUBGGilbert,CriglerNa ajjar, Physiologicjau undiceofnewborn) Blood: UB,AST,CB<20% Stool:Dark D (UBG) Urine: UBG,noCB

Jaundice

Infections Viral(Seebug chartformore info)

Autoimmune

Hepaticjaund dice:hepatocellular,intrahepatic Neonatal:hepaticbiliru ubinglucuronyl Posth hepatic:obstructive(extrahepatic)cholestasis. cholestasis.(C Causesviralhepatitis,alc coholichepatitis transferaselowatbirth.Normalrbc uctisblockedsobilirubinc Biledu cantgotointestine anythingtha atcausesdamageofcellsthemselves). t s(w/HbF). breakdownoffetalrbcs (cause esdruginducedslowedf flow,biliarycirrhosis, Cellsdamaged dandcantconjugatebiliru ubin. Accumulatebilirubinaffectsbasal Dubin nJohnson,Rotors,Gallston ne,PancreaticCain Blood:AST<ALT,ALP,GGT,CB B(2050%) ganglia,causeskernicte erus(toxic ofpancreas). heado ALCOHO OLIChepatitishasAST>ALTW/alcohol, encephalopathy).Biliru ubinbecomes AS,ALT,ALP,GGT Blood:HIGHCB(>50%), youget ttoASTed morepolarw/UVlightbecomes Stool:SUPERPALE(CBcantgetthere),claylike Stool:~NormalUGB,pale/claylik kestool watersolubleandcanbe b excreted Urine:Dark(CB) Urine:Dark D (UB,CB) withoutconjugation. Blo oodborneinfections:syste emicorarisinginabdomen nTB,malaria,amebiasis,staphylococcal,salmonello oses,Candida pidonsetof Viralsystemicinfection:EBV,CMV(neonates,lowimm munity),Yellowfever,Herpe esvirus,adenovirus,rubella,enteroviruses Fulminan ntacutehepatitis:rareH HBV>HAV>HCV.Massiveto osubmassivenecrosis,rap Viralhepatotropicinfection: HAV(food,waterfecaloral), o HBV(parenteral,secretions,perinatal),HCV(pa arenteral,secretions),HDV V(only failure(w within2wksofonset).Fulminantusuallycausedby ydrugs,toxins. osis.Chronic w/H HBV),HEV(waterfecaloral) o Chronich hepatitis:mostHCV>fewH HBV,HDVw/HBV.Mayormaynotprogresstocirrho Clin nicopathologicsyndromes safterhepatitisexposure: usuallyca ausedbyalcohol,virus(no otHAV),NAFLD,toxins,bili iarydisease,HH,Wilsons,A1AT A Acuteinfectionw/reco overy(happensw/allhepatotropicviruses)asx(ser rologicevidenceonly)orsx x o Lo obuleshaveapoptosis,steatosis.Macrophageaggr regates. o Hepaticfailure(e encephalopathy)2wksfro omsxonset.Nostigmataof o chronicdiseaseviralhe epatitisonlycause12%ofcases. o Po ortaltracthasMAINDAMA AGE(lymphocytes,plasma acells). ecrosis. Drug/chemicalto oxicitycause52%(acetaminophencauses50%).Aut toimmune(15%),miscellan neous(mycotoxins,ischem mia, o Ch hronicactivehepatitsinfl lammationatinterfacezonesarebridgedbyne st massivemetasta ases,venousobstruction,fattyliverofpregnancy). Irr reversibledamage(fibrosis s)1 portal,thenperipor rtalzonesarebridgedbyfibrosis. o Necrosisentire eliverorrandomareas.Gr rossliverappearsreducedsize,limp/red,wrinkledca apsule.Cutsurfaceisdusk ky,red, Carrierst tate:HCV>HBV mushy.Microscopically,losecelldetail.Parenchymalcollapse.Pr reservedportalareas.Inptswhodienoinflammat tion. HIVinfec ction:HCV>HBV Survivalmassiv vephagocytosis;postnecr roticcirrhosis:scars+regen neratedlivercellnodules. HBV:DN Avirushasgroundglasscytoplasmandsanded nuclei o LobuleshaveMA AINDAMAGEdamaged/in ndisarray.Theyareinjured(ballooned,apoptosis,se everenecrosis/collapse, HCV:Ste eatosis(focalinlobules),lymphocyteaggregates Kupffercelllipofuscinpigment);responsetoinfection(macrophageaggregates,lymphocytes,plasmacells),Dysfx(chole estasis, Acutevs s ChronicActiveHepatitis Lobulesindisarrayinju ury,inflammation,dysfxinacute.In steatosis). chronica activeseeportalperiport talareainterfaceinflamma ation/necrosis. o Portaltracthassome s inflammation(lymph hocytes,plasmacells,cho olestasisductularrxn) Aut toimmunehepatitis:abno ormalTcellregulation(CD4 4,CD8cellsmediateinjury).Geneticpredisposition, See gammaglobulinswithNO Oserumevidenceofviralh hepa s. env vironmentaltrigger(viralin nfection,drugs,herbs). Types sdeterminedbyspecificse erumautoabs.Usuallyno oantimitochondrial(PBC). Occursinsettingofoth herautoimmunediseases(celiac ( disease,UC,RA,SLE E,SS. US type1ismorecommon(a age10elderly).InEuropeType2ismorecommon(p pediatric) Respondstosteroids,immunosuppression. Morp phology:Classichistology anystageofchronichepatitis+plasmacellclusters satinterfacearea,()bileductinjury. F>M(8:2),W>B,risk kinNorthernEuropeans. Many ymanifestacutely,amypr resentw/fulminantcourse.Ifsevere~40%diein6m mow/outtx,cirrhosis/livertransplant.

Liver/BiliaryTract
Endstagecirrhosis. Irreversible(?)changes. Bridgingfibrosis(central portalzones,thenportal portalzones). Regenerativenodules (micromix+ macronodules;ETOHif ischemicnecrosisbroad d scars(Laennecscirrhosis) ), Endstage(shrunken, brown),Vascular reorganization(endstage nonspecifichistology. Mallorybodiesarerare now) AlcoholicLiverDisea ase Nonalc coholicfattyliverdisease: :Steatosisw/minorinflammation;steatohepatitis(NASH).Histo Pathogenesis:activecelldamagehepa atocellular andcha angessimilartoalcoholicli iverdisease damage(ballo ooningandnecrosis);Mallo orybodies N NASH(nonalcoholicsteato ohepatitis)adxofexclusi ionhighserumaminotransferases, (cytokeratinbundles b incytoplasm),Neutrophils G GGTP.Alcoholintake<20g g/day,labtestsnegativefo orHBV/HCV,negativeFestudies, arounddamag gedhepatocytes,earlydelicatefibrosis n negativeautoimmunesero ology.M=Friskfactorsar reobesity/metabolicsyndr rome. aroundcentra alvein(chickenwirefibrosis s),Steatosis C Componentshyperinsulin nemia,obesity,dyslipidem mia,hyperlipidemia,HTN,type2DM. aroundcentra alveininitially(alwayspres sentinNASH). M Mostcommoncauseofchr ronicliverdiseaseinUS.~ ~30%ofAmericansaffected d(70%of Macrovesicula arlipidincells(centrilobula ar). o obeseindividuals) 2hithypothesis:fataccumulation+oxid dativestress. C Canstopprogressionofste eatosis,butNOTreversible einNASH. o Inmoststeatosiscases,ptsareasx.Dxisoften C CanprogresstoAdvancedf fibrosis(3040%ofpts),cir rrhosis(1020%ofpts),hepatocellular incident tal,duetofindingliverenzymes. e c carcinoma(?Biggerinthepastbecauseliverdiseasewasdiscoveredlater) ALTAST T~1.52Xnormal;ALT>AS(reverse ( of 4findin ngsnonspecificfindingsth hattogethershowNASH/A Alcoholicliverdisease: ETOHhepatitis).AdvancedNASH/ /cirrhosis H Hepatocytedamage(swelling/necrosis) w/norm malliverenzymescanoccur.Causeof M Mallorybodies(cytokeratinfilamentsindamagedce ells) mostca asesofcryptogeniccirrho osis. N Neutrophilsatdamagedce ells o Sympto omaticfatigue,malaise,or o vaguedull F Fibrosis:perivenularearly( (chickenwireatcentralve ein) RUQab bdominaldiscomfort. + Steatosistriglycerideaccumulation(microvesicula arfat,initiallycentrilobular rthendiffuse). Wilso onDisease A A1antitrypsindeficiency Labs:Ele evatedliverenzymes,hepa atomegaly, Patho ogenesis:Defectiveexcret tionofcopperinto AbnormallylowserumlevelsA1AT(AR). cirrhosis.Elevatedbilirubin,transa aminases.EKG bile.Copperaccumulatesinliv ver>brain,eye,other A1ATproducedbyli iver,fxasproteaseinhibito orofelastase, QRS,Twavea ened/inverted. .Assoc organ ns.Toxictissuedamageis duetocopper cathepsinG,proteina ase3releasedbyneutroph hilsatsitesof w/hypot thyroidism(fromfibrosis,development d of cataly yzedROS.WNDgeneisAT TP7B,encodesan inflammation. antithyro oidabs).1/31/2havearth hropathy ATPaseenablingcoppertransp portacrossthe Deficiencylungtissuedestructionemphys sema. (resemblesosteoarthritis). canal licularmembrane.Mutatio oncapacityto Cirrhosisdevelopsthr roughaseparatemechanis sm!Most Causes:FamilialForm:ARinheritan nceofHFEgene incor rporatecopperintocerulop plasmin commonnormalgeno otypePiMM.Commonestsignificant (C282Y,H63D), H onsetage4050,lo owhepcidin ceruloplasmin.Lessceruloplas minmeansless deficiencyvariantP PiZZ.WithPiZZgenotypeA1ATlevels levels.Hepcidin H circulatinghorm monesynthesized copperexcretedbile(thebo odysmaincopper es(PiZM)have ~10%normal;riskfordisease.Heterozygote inliver,regulated r byironstores/inflammation eliminationmechanism).>300 differentmutations, intermediateA1ATle evels. actsonferroportin f toinhibitirontransport. notallcauseWND. Ep pi:Mostcommonlydxped diatricgeneticliverdisease ecansee Se econdaryCauses:Thalassem mia, sh hortlyafterbirth Sid deroblasticanemia,Chronicliverdisease Cause e:MostWND(AR):compo oundheterozygotes Pa athogenesis:100%ofPiZZ Zgenotypes(normalPiMprotein (H HCV,HBV,Steatohepatitis,Alcohol A assoc 2mutated m alleles,eachw/diff fferentmutation. m migratesfromERGolgia apparatus)PiZvariantpolypeptideis liv verdisease),multipletransfusionsseen ab bnormallyfolded.PolymerizesandaccumulatesinlivercellRER. moreinmales(becausewom menmenstruate) Sx:pr resentsafterage5.When nnonceruloplasmin O Only1015%PiZZdevelopc clinicalliverdisease(?Othergeneticand boun ndcopperspillsoverfromllivercirculation, en nvironmentalfactorshep patocyteinjurycausedby Dx:highlevelsofserumiron,ferrit tin;exclusionof other rorgansaredamaged.Bra ain,cornea,kidney, tionofNFkB au utophagocyticresponse,m mitochondrialdysfx,activat secondarycausesofironoverload, ,liverbiopsyif joints s,bones,parathyroidgland ds.Highurinary aseresistant). pa athway).Hyalineglobules sincytoplasm(PAS+,diasta indicated d(showinghepatocytessta ainingdarkw/ copperexcretion(screeningtes st).Brain d/adolescent Neonatalcholestasishepa atitiscirrhosis.Childhood Prussian blue).Importanttoscreen nfamily involv vementofbasalgangliap putamenhas he epatitiscirrhosis.Adultcirrhosisdefinitelyseen. member rsforhighserumiron,ferri itin(?transferrin atrop phy/cavitation, leading to n neuropsychiatric Sx x:canvaryallthewayfrom mhepatitis(cholestasis)tocirrhosis saturatio on>60%M,50%F).Heterozygotesusually manifestations.KaiserFleische erringsinmost (n needlivertransplant).Emp physema(avoidsmokingrecruits havelow wofreallyloworgandamagenormallife cases sgreen/browncopperde epositsin Zadults+/ ne eutrophilstolung).Hepat tocellularcancer(23%PiZZ expectan ncyiftx/dxprecirrhosis. Desce emetsmembraneincorne eallimbusbyslit ci irrhosis. Tx:usuallyregulartherapeuticphle ebotomy, M Morphology:hyalineglobul lesincytoplasm(PAS+,diastase chelation nw/deferoxaminenotusuallydone lampexam(supportsWNDdx).. re esistant).Onlydistinctivef featuresteatosisisclueinneonates. Morp phology:livermorphology y isnotspecific. Steat tosis,acute/chronichepatit tis,macronodular cirrho osis.Massivenecrosisisra are.Rhodanine stain showshightissuecopper (nonspecific) PAS+ Dx:ti issuecopperlevel>250um m/gmdrywt. Tx:livert transplantation. gue,then Sx:F>M(6:1),2080yrs,peak4050 0yrs.Onsetpruritis,fatig taofcirrhosis. xanthoma as,xanthelasma.Latejaun ndice(liverfailure),stigmat Labs:anti imitochondrialabs(~95%) ).Earlyserumalkalinephosphatase, p GGMTandcholesterol.Lateh hyperbilirubinemia. Tx:livert transplant ephosphatase Sx:70%h havehxulcerativecolitis.A Asxpersistentalkaline ourseismany levels.Sx xprogressivepruritis,fati iguejaundice.Diseaseco kof years(51 17).Lateseveredisease,st tigmataofcirrhosis,risk cholangio ocarcinoma.Duetochronicinflammation.Alsoriskof o chronic pancreatitis,hepatocellularcarcinoma. CaroliDisease:Dilatedlargerducts ofintrahepaticbiliarytreeAR

Drug/Toxin Induced Disease:

exposureto toxin/therapeut icagentshould alwaysbe includedinDdx ofliverdisease

Gros sssoft,greasy,yellowliver. .Wtis40006000gm. Alcoholicscanreverseitwithabstinence. a Continued ETOH Huseriskofinjuryand dbrosisthatmay leadtocirrhosis(1020%). Hem mochromatosis

Metabolic LiverDisease

Path hogenesis: Lostregulationofdietary yFeabsorption.0.51.9gm m/yradded, presentsafter~20gmac ccumulate.Sxatage4060 0yrs(sxlater inF).Fetoxictotissues(generatesROS)lipidpe eroxidation, stimulatesstellatecellsto t collagen.**Hemosiderin deposition,Cirrhosis,Pa ancreaticFibrosis** Feaccumulatesinmostly yparenchymalorgansliv ver(+20gm, normal~0.5gm),pancre eas,skin(melanin+hem mosiderin), >heart(brown,enlarged),>endocrineglands(fx x),>joints (acutesynovitis,pseudog gout),Hypogonadism(test tes). Hereditary(AR)geneticdefect d ofFeabsorption(HHtotal bodyFecontentregulate edthroughabsorption,not texcretion hepcidinproteinprevent tsironreleasefromintestinalcellsto plasmadeficiencycaus sesFeoverloadotherpro oteins regulatehepidinlevels.Genemutationslackof fhepcidin expressionHH.HFEgene g C282Ymostcommo oninadultsa channelthatisinsmallin ntcryptcellskeyinFeab bsorption, NorthernEuropeanCauc casians11%areheterozy ygotes,only 20%penetranceinhomo ozygous,M:F6:1,Secondlesscommon gene=H63Dhistidinetoaspartateatposition#6 63)AR;or duetointake(mostlyfromparenteraltransfusio ons). Sx:U Usuallyasxatdx.CausesBronze diabetesGlycos suria (diab betesviadepositioninBce ellstoinsulinproduc on nanddirectly impa airedinsulinsensitivity),br ronzeskinpigmentation(gray/brown patch hes,canbeseeninmouthprobablysecondaryto mela anin/irondepositionaroun ndsweatglands),cirrhosis.fatigue, atypicalarthritis,hepatomegaly,arrhythmias,cardiomyo opathy, impo otence,(infection).Deathcirrhosis,cardiacdisease e, hepa atocellularcancer.200X riskofhepatocellularcarc cinoma

Prim maryBiliary Cirrh hosis

Intrahepatic BiliaryTract Disease

Prim mary Scler rosing Cholangitis

Pathogenes sis:Intrahepaticbileductdestruction d (mediumsized).Chronic,progressivenon n suppurativeportalinfla ammation,scarring.Insidiiousonset, nosxforyears.Leadstocirrhosis,live erfailure,death.riskofhepatocellularcarcinoma.Autoimmunee ology?Ab A antimitochondrialIgM M,others. Assocw/oth herautoimmunecondition ns.DonebySTELLATECELL LS Morphology y:portaltractsareinflame ed(floridductlesion)lym mphocytes,plasmacells,+/eosinophils,Ductdestruc ction+/granulomatousre eaction. Eventualint trahepaticobstructiontoflow f ofbile.Upstreambile b stasisleadstohepatocy yteinjurycirrhosis.Obse ervegreen,micronodulars smallerliver. Pathogenes sis:Processaffectingbothintraandextrahepaticbile educts.Inflammationw/o obliterativesclerosisofsom mesegments.Dilationof f intervening nonscleroticsegments.Classicbead dedpatterninradiograph hiccontraststudies.M>F(2:1), ( 2040yrs.Maybeim mmunemediatedgutactiivatedT cellsorbact terialiver.crossreactw/bileductags.Absan ntismoothmm,antinucle ear,atypicalpANCA,rheum matoidfactor. Morphology y:affectedductslympho ocyticinflammation=chola angitis.Concentricperiduc ctalstromalfibrosis=sclerosis.Resultsinprogressiv ve stricture/ob bstructiontobileflow.Bile eductseventuallyatropyand a disappearreplacedbysolidcordlikescar.Interveningnonscleroticduct tsdilated, inflamedbile b stasisleadstohepatoc cyteinjury.Endstageisno onspecificbiliarycirrhosis. . VonMyenb burgComplexes: closeto/wit thinportaltracts, smallclustersofdilatedbile ductembed ddedin fibrous/hyalinizedstroma. Fromresidu ualembryonicbile ductremnantsSporadic Poly ycysticLiverDisease: Mult tiplecysticlesionslined bycu uboidalflattenedbiliary epith helium,containstraw coloredfluid,F>MAD, asso ocw/ADPKD CongenitalHepa aticFibrosis: portaltractshave ecollagenous tissue,separatelliveroddly persistentmalfor rmed embryonicbiliary ytreefibroses overtimeAR,a assocw/ARPKD

Anom maliesof theB Biliary Tree e (inclu uding livercysts)

Liver/BiliaryTract
Congenital

Ala agillesyndrome Imp pairedbloodflowto live er

Circulatory Disorders

Imp pairedbloodflow thro oughliver

Syndromic S paucityofbileducts d theductsarentpre esent.DuetomutationofJagged1onChromosome20p Centrilobular C necrosis(Lsi idedheartfailure,shock)hepaticarterycompromi ise,portalveinobstruction n,intra/extrahepatic thrombosis.Centrilobularhypoperfusion/hypoxiaischemicnecrosis.Seees sophagealvarices,splenom megaly,INTESTINAL congestion c Combination: C Sinusoidocclusion(sicklecellanemia,DIC), D systemiccirculatorycompromise, c cirrhosis.See eascites,esophageal varices, v hepatomegaly,elev vatedtransaminases. centrilobularhemorr rhagicnecrosis==thisisth hegrossmottledliverwithNUTMEGappearance.Redtissueiscongested (centrilobular),paletissue t isviable(periportal) ).Microscopically,seecongestednecroticcentrilobu ularareas,viable periportalareas. PeliosisHepatis:ster roid,oralcontraceptiveusemayleadtosinusoidaldi ilation.Usuallyasx,butmayhavepotentiallyfatal intraabdominalhem morrhageorhepaticfailure e.Lesionsgoawayaftertxstopped. Chronic C passivecongestion n(Rsidedheartfailure)centrilobularcongestion,hepatocyte h atrophy.Hepaticveinthrombosisin Budd B Chiarisyndrome.See easciteshepatosplenomeg galy,abdominalpain,eleva atedtransaminases,jaundice AcuteFattyLiverofP Pregnancy IntrahepaticCholestasisof fPregnancy Womanin3rdtrimeste er Sxfromhepaticfailure re(bleeding,N/V,jaundice, ,coma).2040% P Pruritisonsetin3rdtrimest terfollowedby havepreeclampsiaw/ /this. d darkeningurine,lightstool ls,jaundice Dx:confirmmicrovesiicularsteatosisw/Sudanblackstain.Difficultto G Generallybenign,butmom matriskfor distinguishfromhepa atitis. g gallstones,malabsorption,someof f fetaldistress,stillbirths,prematurity Tx:terminatethepre egnancy MetastaticNeo oplasms morecom mmonthanprimarytumo ors Multiple breast,lung,colon,panc creasaremostcommon origin Anycanc cer,especiallyfromorgans sdrainedthroughportalve ein toliver Classic multiplesmallernodulesi inenlargedliver.Often clinically silent.Ifsingleorfew,no odulesmightberesectable. Hepatoblastoma(pedi iatric) Mostcommonchildhood c liver tumor(~80%,bu utrare).Most casesininfants~1 ~ yr.riskif prematurew/low wwt.M>F (2:1),W>B(5:1). . malformations s,nocirrhosis. Solitary,solid/ta antumor.Well circumscribed,bulging. b Asx abdominalmass s. Smallroundimm mature hepatocytesincords c 2patternspur reepithelialcells ormixedepithelial+ mesenchymaltis ssues(cartilage, bone,striatedmm), m teratoma like.Genetics mutationsin WntBcateninsignaling s pathway. Arisefromapluripotentstem cell,mimicsnorm malfetalliver development. ReallyhighAFPlevels. Mayhavefocalhematopoiesis h likenormalfetal lliver. Completeresect tion+chemotx ==80%5yrsurv vival. Angio osarcoma (thoro otrastassociatedw/ riskof fangiosarcoma,HCC, cholan ngiocarcinoma;PVC, arsen ic) Rare,3rdmostcommon primarylivertumor. Riskw/exposureto PVC,arsenic,thorotrast. Lowgradeproliferation n ofmalignantatypical, plumpendothelialcells thatformvascular spaces. Highgrade cellularity,solid, abnormalmitoses, spindled.Endothelial originhas+stainsfor Factor8,CD31. Cholangiosarcoma (PSC,chronicinflamm mation/infection) Malignancyofbileductepithelium(adenocarcinoma). 90%ariseinex xtrahepaticbileducts.UShas otarisein incidenceofint trahepatictumors.Dono cirrhosis. Riskfactors(mostcasesarewithout):clonorchis sinensisinfection,thorotrastexposure,congenital intrahepaticdu uctdilation,HCVinfection common MixofCCA+HCCpossibleduetooriginfrom f precursorcell. Invadingductscausedesmoplasticstromalresponse, hard/grittywhitetumors

Hep paticvenousoutflow obs struction

Pre eeclampsia,Eclampsia 710%ofpregnanciesHTN,proteinuria,peripheraledema,coagulationabnorma alities,sometimes asp pectsofDIC. Hepatic Ecc clampsiawhenassociated dw/hyperreflexiaandconv vulsions Disease HEL LLPsyndrome:hemolysis,elevatedliverenzymes,low wplatelets w/Pregnancy Live er:periportalsinusoidscon ntainfibrinw/hemorrhageintospaceofDisse(getpe eriportal hep patocellularcoagulativene ecrosis).Cangethepatiche ematomaanddissectionof o bloodunder Glis ssonscapsule(mayruptur re) Livercelladenoma(be enign): Mostinyoungfe emales,assocw/longterm museoforalcontraceptive es.Alsomen,assocw/anabolicsteroids. Glycogenstorag gedisease Mostsolitary(80%).Oftenbeneathlivercapsule.530cmdiameter, d welldemarcated d.Tan, yellow/greenfro ombile. Microscopic:pro oliferatinghepaticytesinsheetsandcords,oftenlooklikenormalcells.NObile eductsorportal triads.Largeblo oodvessels. Dangerssubca apsularrupture,bleeding,especially e inpregnancy.Rarelycontainortransformto hepatocellularc carcinoma.OftenmisdxasHCC. Malignant Hepa atocellularcarcinoma/HCC C(HBV/HCV,ETOH,HH) Hepatocellularlamellarvariant(no Neoplasms Mostcommonprimarylivercancerworldwide.M>F M (2:1). cirrhosis) Mostcasesgloballyarerelated r tochronicHBVinfe ection. Fibrola amellarvariant:5%ofall Otherfactorschronicalcoholism, a nonalcoholicfatty f liver HCC.20 2 40yo,M=F.NO disease,chronicHCVinfe ectionw/cirrhosis,aflatoxi in.Also setting gofchronicliverdisease hereditaryhemochroma atosis,A1ATdeficiency,glycogen (noHB BV,cirrhosis)prognosis storagedisease,heredita arytyrosinemia.Cirrhosisalso better. .Large,hardtumor playsavariablerole.Chronichepatitiscyclesof f transec ctedbythickfibrous death/regenerationaccumulation a ofDNAmutations. bands (collagenlamellae). Classiconelargetumo orw/manysatellitetumors(or Welldifferentiated multiple/diffuse)allcauseanenlargedliver.Pale e,green hepato ocytes.Eosinophilic, frombile.Invadehepati icbloodvessels(especially yveins). abunda antcytoplasm Proliferatinghepatocytes.Welldifferentiated (mitoch hondria),prominent anaplastic(doesntlooklikeliver). nucleoli Clinicalfeatures:sxrelat tedtochronichepatitis,cir rrhosis. Vagueupperabdominalpain,malaise,fatigue,wt. Senseoffullness,mass.Liverenlarged,palpable nodularity,distinctfromcirrhosis.Jaundice,fever, , esophagealorGIbleedin ng. LabsserumAFP(10 00Xnormal)butCEAnot .(AFPis alsoingermcelltumo ors,rarelyw/cirrhosis,hepa atitis, posttraumaticregenera ation)

TheBiliaryTra act

1Lsecretedperday;Hasacapacityof50mL.Gallbladdernot re equiredforbiliaryfx. H Hasnomuscularismucosae eorsubmucosaonlyhasamucosa lin ningw/asinglelayerofcolumnarcells,afibromuscularlayer,a la ayerofsubserosalfatw/arteries,veins,lymphatics,nn, n and paraganglia,andperitonealcoveringexceptwheregallbladder embeddedintheliver

Normal

Congenital Anomalies Above:a

Majoranomaliesarera are Gallbladderabsent,duplication, d bilobed,folded dfundus(Phrygiancap),ab berrantlocations(510%) Bileducts:mayhaveag genesisofallorpart(withotheranomaliesinspleen/ /heart/GItracttheonesidedstructures),atresia a(fetalperinatal) P Phrygiancapfrominfolded dfundus

Ch holesterolstones (80%ofthosefoundinwes st,industrializedcountries)

Pigment(bilirubin n)stones
predominantforminno onwestern countries

Cholelithiasis

Cholecystitis
Acuteorchronic, acutecanbe superimposedon chronic.Nearly alwaysoccur w/gallstones. InUS,oneofthe mostcommon indicationsfor abdominal surgery. Epidemiologic distribution closelyparallels thatofgallstones

Disordersof Extrahepatic Ducts

indevelopingcountries,Asia.unconjugated dbilirubinin Mo orphology: Mucushypersecretio on(scaffoldingandcement tallowssustained bile.Mixtureofabnormalinsolublecalciumsalts sofUB Contain50100%chole esterol(100%cholesterolare a rare).Radiolucent,yellow.Mosthave crystaltrapping,aggr regation,growth) w/inorganiccalciumsa alts.Infectionofbiliarytractcauses mixedcomponents.Ca anberadioopaque(1020 0%)addgray,white,black kcolors. Clinical C features: releaseofmicrobialBg glucuronidaseswhichhydr rolyzebilirubin Singleormultiple.Mm m(gravel)tocm.Rounded, ,barrelshaped,orfaceted d(formedintight 75%areasxforyrs/d decades.14%peryrdeve lopsx(riskw/ me). glucuronidesandun nconjugatedbilirubiningallbladder apposition) Mainsxbiliarypain n.Thisissevere,usuallyin RUQ.Constantor Blackgallstones:forminsterilebile,gallbladderindicate Ris skfactors:4simultaneousdefects: intermittent(colicky y)relatedtoobstructiono ofbileexcretion.Also Supersaturatedbile( cholesterolsecretionbyliver)Conditionsthatchangebile relatedtogallbladderinflammation(cholecystiitis). chronicintravascular rhemolysistoomuchthe erefor compositionchole esterolconcentration(ag ge,female,femalesexhor rmoneslike Complications chasbypass conjugationandprecipou ut,severeilealdiseasesuc estrogen/progesterone e,contraceptives,pregnancy,weightobesity,rapidwtloss;D19Hgene o Obstructionbile b ducts(obstructivecho olestasis),pancreatic surgery).Radioopaque,many<1.5cm,crumble,speculated, variantproteininvolv vedincholesterolsecretion nhyperlipidemiasyndrom mes),bilesalts ducts(pancrea atitis).Smallstones/grave elhaverisk.Large molded. (inbornerrorsofbileacidmetabolism) stoneshave riskbuterodeintoandob bstructthesmallbowel Browngallstones:form mininfectedducts(bacteriaor Gallbladderstasis(free echolesteroltoxictowall;nucleationintocrystals) )riskw/acquired (gallstoneileu us) umsoaps parasites)theyarerad diolucentmadeofcalciu hormonal,nervedisord ders(spinalcordinjury),starvation(prolongedtotalparenteral p nutrition) o Empyema,per rforation,fistulae,inflamm mationofbiliarytree sthis).Soft, (glucuronidaseunconjugatesbilirubinandforms Acceleratednucleation n(proantinucleatingpr roteins,calciumsaltmicrop precipitates) o riskofgallbladdercarcinoma soapy,greasy Acu uteCalculousCholecystitis s(inthepresenceofstone es): AcuteAcalculousChole ecystitis: ChronicCholec cystitis: Chemicalirrita ation(NOTbacterialinfe ection)inflammation Ischemia/poorperfusion(NOTcausedby Likelyar resultofgallstones+lowle evelacuteinflammation.L Longterm,somereportantecedent gallstones)cyst ticarteryisanendarteryithas %ofcases). attacks. Sxsimilarasacutecholecy ystitis.Gallstonesroleno otclear(butpresentin90% resultingfromobstruc ctedgallbladder90%nec ckorcysticduct nocollaterals. riskofgangreneand Samerisk kfactors.Obstructionisntnecessary.Similarsx/mo orphologycalculi. obstruction.Bilelecith hinsarehydrolyzedbymuc cosalenzymes.Atoxic perforation.Tendtohappeninseverelyill 1/3ofca aseshavemicroorganisms(E.coli,enterococci) form(detergent)candisruptmucuslayertissu ueexposedtoirritating hospitalizedpt(+ +additionalriskfactorsse evere erecases, Morphollogy:Lymphocytes,plasma acells,macrophagesfrommucosatoserosa.Inseve bilesaltscanbecomeinflamed. trauma,burns,se epsis/infection,hypotensio on MuraltissueswellingPGreleaseinflammat tiondysmotility ion. fibrotic/t thickwalls.Rokitansk kyAshoffsinuses benignreactiveproliferati w/multisystemorgan o failure,DM, furthertissueswellingmucosalbloodow(riskofnecrosis, Epitheliu umpouchesdown,insinuat testhroughwall.Mimicsa adenocarcinoma. hyperalimentatio on). perforation) ;stones Grossmo orphology:mucosanotulc cerated,tanwhite.Lumen nclear,mucoid,greenbile; Insidiousonsetofsx(obscuredbyserious Clinicalfeatures:progr ressiveRUQorepigastricpain.Mildlyfebrile, usuallyp present.Wallthick,opaq que,graywhite.Serosa:sm mooth/adhesions. precipitating con dition, often sx not gallbla dder anorexia,tachycardia,sweating,nausea/vomiting gabdominal porcela in(calcified)gallbladderriskofassociatedcarc cinoma related,dxneeds sindexofsuspiciontoavoid tenderness.MildlyWBCs, W mildlyserumalkalinephosphatase Hydrops psofgallbladderclearfluidfillslumen(longtermc completeobstruction) mortality!) (obstruction).Hxofpr reviousepisodeislikely. bilirubinandjaundice Clinicalfe features:similartoacutecholecystitisbutrecurrent,indolent.Fattyfoodintolerance. Morphology:Acu uteinflammatoryrxn ONLYw/commonbileduct d obstruction.Bacteria alcontaminationand Complica ations:bacterialsuperinfection,perforationabsce ess,ruptureperitonitis, (neutrophils,vasc cularcongestion,edema infectionmaydeveloplater.Maybeasurgicalem mergency(orptmay cholecyst tentericfistula,aggravatio onofpreexistingillness grosslyenlarged,tenselumenhasbloody ybile havemildsxthatresolv vebutrecur) pus,stones;mucosaishyperemic/red,wall thick/edematous s,serosahaspus/fibrinexu udates) IndifferentialDx xofacalculousvscalculous, therearenospec cificdifferences Cho oledocholithiasis:stonesinthebiliaryducts(generallyCBD) AcuteCholangitis:Bact terialinfectionofbileducts s Westcholesterolston nesformingallbladder(ste erile),traveltoducts Duetoobstructio ontobileflow.Stone(cho oledocholithiasis)ismostco ommoncause.Bacteriaas scendthroughsphincterof fOddi.Tendtobecausedbyenteric s.Ascending Asiahighincidenceof o brownstoneformationin nducts(infected) gramnegaerobe es(Ecoli,Klebsiella,Clostrid dium+bacteroides,Entero obacter,Interococcus).Ot thercausescatheters,pa ancreatitis,otherinfections Ptsareasxorhavesxdue d to: cholangitis:infec ctionintrahepaticducts. o Obstruction(bile echolestasis,pancreatitis) Sx:Feverandchills,abdominalpain,jaundice(classicsxtriad). o Infection(acutecholangitis,liverabscessor o cirrhosis) Morphology:Muralneutrophilsmovetowa ardinfectioninductlumen n. o Concurrentacutecalculouscholecystitis Suppurativeacut techolangitismostsevereform.Purulentbilefills/ /distendsducts.Sepsisism mainclinicalfeature.

TheBiliaryTra act
Com mplete/partialobstruction nofextrahepaticbiliarytre eelumenby3monthsof o Effectsofintrahepaticcholestasis sinliverbiopsy(2/3cases s)Parenchyma age e (cholest tasis),bileductules(prolif feration/regeneration),Po ortalareas Perinatalform:80%.(mostcommon)bornw/n normalbiliarytree, (edema a/fibrosis). destroyedafterbirth.Theoryamultihitprocessisresponsibleforinjury. . o Paucity yofbileducts(1/3cases) Geneticpredisposition,autoimmunity.Viralinfectionofbiliaryepithelium Clinicalfeatures:Ne eonatalform:slightF>M,Asian/African>Caucasian A in nUS.Normalwt/stools (reovirus,rotavirus,CM MV) initiallyacholic.Bilirubin~612mg/dL(no ormally<1.0mg/dLby1mo onth).Moderately Fetalform:20%.Abno ormalintrauterinedevelop pmentoflaterality.Other aminotransferases(cellinjury)andalkalinephosphatase(obstruc on) ).Cirrhosisbyage36 anomaliesofonesided dorgansassociated. month(secondarybiliarycirrhosis),deathbyage a 2yrs.Txlivertranspllantationforcure Morphology:inflamma ation+fibrosisofextrahepaticductsleadsto (surgicalresecetion/ /bypassifptproximalbileduct d branchesBUTbacteriialcontaminationand stricture.Onceductshave h narrowedlumen,the engetintrahepatic diseaseprogressionafter) cholestasisperiduct tuleinflammationseco ondarybiliarycirrhosis. Choledochalcyst:cong genitaldilationofthecomm monbileduct.Mostptspresentbeforeage10,F>M M(34:1).Ptshavejaundice e,recurrentbiliarycolilike eabdominalpain.RUQma ass.Complicationsstone eformation,stenosis,strict ture, pancreatitis,secondary ybiliarycirrhosis,riskof fbileductcarcinoma(inolderpts) Tumors: Ade enomas:similartoelsewhe ereinGItract Infla ammatoryPolyps:inflamed dmucosalprojections Ade enomyosisofgallbladderbenignintramuralglandsw/stroma w inahyperplastic cmuscularis.Canmimic carc cinoma. o Gallbladdercarcinoma Car rcinomaof Uncommon,F>M,older. Gallbladder Pathogenesisirritation,traumachron nicinflammation. Stones/west,infection/Asia Sitesfundus/n neck. Adenocarcinom ma(invasive)mostinfiltrateintoliver,exophyticmasses. Insidiousgrowth(incidentaldx,almostne everpreop,atdxmosthav veinvadedliverviabile ducts,lymphno odes) Asx,RUQpain,anorexia, a N/V,wtloss.50%havejaundice. Unc common,M>F,older Irrit tation,traumachronicin nflammation. Due etostones,parasiteinfecti ion. Car rcinomaof Prim marysclerosingcholangitis. Ext trahepatic Ulce erativecolitis,choledochalcyst Bile eDucts Ade enocarcinoma(invasive)most m infiltrate,ductalsm mall,obstructing/firmgraynodulesofwall;fibrousStr romalrxntoinvasion.Pap pillary. Klat tskintumoratjunctionof fR/Lhepaticducts,slowgrowing,rarelymetastasize e(thisparticularvarianthasabetterprognosis) Sxpainlessjaundice.HIGHserumalkphos,higham minotransferases,HIGHdire ectbilirubin,hepatomegaly y(50%),palpablegallbladd der(25%) Needlethrustfromper rcutaneousliverbiopsy/tra anshepaticcholangiograph hy Bileleakageintoperito oneumcancausebileperitonitis(inflammationinper ritealcavity) Chemotxagentsinfuse edintohepaticarterycancause c druginjuryofbiliarytree Biliarystrictureafteroperativetrauma(seenw/la aparoscopiccholecystectomy)10%associatedw/pancreatitis,externaltraum ma Stricturesofcommonbile b ductproximaltocystic cduct=usuallymalignant.

BiliaryAtresia

Choledochal Cysts

Tumors

Iatrogenic Injuryto BiliaryTree

Pancreas
Emb bryology:madefromfusionof fdorsalandventraloutpouchin ngsof fore egut(wk7) Sec cretin:stimulatesreceptorsthatactivateadenylatecyclasean ndinitiate bica arbsecretioninductcells,ScellsinduodenumstimulatedbyH+(max secretionatpH3),luminalFA CCK K:promotesdischargeofdigest tiveproenzymesbyacinarcells s,stimulated byF FA,peptides,AAs Proenzyesreleased:(activatedbybrushborderenteropeptidase ein duo odenumlumen,activatedtryps sindoesthistoo)Trypsinogen n, Chy ymotrypsinogen,Procarboxype eptidase,Proelastase,Allikreino ogen, ProphospholipaseA/B.Thereisatrypsininhibitorinthezymoge engranule soe enzymesarentactivatedinthe ere. Adv vantagesofmaintainingintraluminalpHatnearlyneutralvalu ues Preventsacidpepsindama agetoduodenalmucosa ProvidesfunctionalpHforpancreaticandbrushborderenzymes e solubilityofbileacidsan ndFA Sec cretionsofthePancreasandth heirfxs Assecretoryrates r change,the electrolyteco ompositionof pancreaticsecretionchanges:Low flowrate(Na+ +/Clpredominate, LowK/HCO3);highflowrate (bicarb,Na+predominate, p low Cl/K+) Cys sticFibrosis:CFTRis def fective,preventsClrecycling ductsecretionresultingin thic cksecretionandplugging. Itsthemostcommonlethal gen neticdisorderofCaucasians. Inabilitytorecyclechloride req quiredforbicarbsecretion. CFptshavesecretionof pan ncreaticenzymesand pan ncreaticinsufficiency (me echanismunknown).Causes maldigestion,malabsorptionof nut trients(onlyoccurswhen 90% %ofpancreasfxislost). Pancreaticsecretion: Cephalicphase:sigh ht/smell/eatingAcinarcell stimulatedtoreleas sesecretionsbyAch,VIP(Ach potentiatesactiono ofsecretin.) Gastricphase:stom machdistension,amino acids/peptidesingu utlumenstimulate mechanoreceptors causevagovagalreflexeffer rent vagalfiberscauseg gastrinreleasefromGcells(whichact asendocrineonpan ncreaticacinarcellsecretion) Intestinalphase:th hemostimportantphaseiniti iated byentryofgastricc chimeintointestinallumen chemoreceptorsdu uodenum(Scells)detectacid,r release secretin(stimulates sbicarbsecretionbyductcells. .I cellsdetectfat,rele easeCCK(actonacinarcellsecretion ofenzymes).CCKth houghttoactivatevagovagalr reflex

Normal

Ac cinarcells:secrete dig gestiveenzymes. Sti imulatedbyCCK, Se ecretionrate0.2 0.3 3mL/min

Enzym mes:secretedinzymogenform mandstored inzym mogengranules. Bicar rb:secetedbyductcellsviaCl/HCO3 excha anger(apical)drivedependsonduct lumin nalCllevels;luminalmembran neCFTRCl channeliskey(regulatedbycAMPdependent d kinas se). Ectopic (usuallyinsmallintestine/stomachwall)~1 1cm nodule,inpylorusitmayleadtoinflammation n, edema,obstruc ction.Apotentialsiteofisletc cell neoplasms. Canleadtoant tisusscesptioninMeckels diverticulum.

Pancreaticdivisum m Failedfusionofdu uctsystemsdorsal +ventralprimordial.Smallductof Santorinidrainsmostofpancreas. Canleadtochronicpancreatitis 310%haveit

Age enesis Congenital Anomalies inadvertentduct traumaduring surgery/endoscop ycanleadto pancreatitis Usu uallyassociated w/w widespreadsevere mal lformations inco ompatiblew/life IPF1 1iscritical

Conge enitalCysts anoma alousducts.Canbeinpancrea asalone(sporadic)orcoexist w/kidn ney/livercysts(ADPolycysticKidneyDisease,VHLdisease w/brain/renal/retinalvascularneoplasms) Micros scopiccystslarge(5cm).Th hinfibrouscapsule.Singlecell epithe eliallining,mucoid/serousfluid.

Annular Ventralprimordiumfuses nd w/head.Formsringin2 partof duodenumresultsinduodenal d obstruction Sx:gastricdistention,vo omiting

Acutepancreatitis:Revers siblediffuseinflammatorycond dition.Pancreaticsubstanceisdestroyed.Activation+releas seofproteolyticpancreaticenz zymes. Causes:IntheWest80%o ofcasesassocw/alcoholism(M M>F),(65%UScases),biliary tractdisease(F>M,gallsto onesin3560%).Tissuechange eswilldetermineclinical featuresmildedema/int terstitialinflammationtosever rehemorrhage/parenchymal necrosis. Sx:abdominalpain(mildtosevere),constant/intense toupperback.Alsoano orexia,N/V.HIGHserum amylase24hrs,thenlipase ein7296hrs.Glycosuriain 10%ofcases(endocrinetissuedestruction). Hypocalcemia,calciumsoa apsprecipitateinnecroticfat. Toxicenzymes,cytokines,inflammatorymediators circulationsystemicinfl lammatoryresponseshock (vascularcollapse) Pathogenesis:pancreaticautodigestion a byinappropriate elyactivated proenzymesproducedbyacinar a cells.Triggeringevent trypsinogen trypsin.Trypsinactivat tesproenzymes(prophospholip pases membranes,proelastasebloodvessels,prekallikrein clotting: damage),lipase,amylaseare a secretedinactivatedform (levelsare

Chronicpanc creatitis:Parenchymaldestruct tion,inflammation,fibrosispermanent. F). Irreversible inglandfx.Fibrogeniccytok kinespredominate(TGFB,PDGF Cause:multipleattacksofacute pancreatitis( (?),longterm damage(alco oholabuse,duct obstructiontrauma,calculi, divisum,tum mor,CF;hereditary pancreatitisPRSS1,SPINK1) Morphology:hard,dilatedducts +intraductalcalcifications. Parenchymalfibrosis,lostacini (number/s size) Sx:p painprecipitatedbydemandsuchas ETOH/eating;sphincterofOdditone opia ates/otherdrugs);canbesilent(firstsignis insuf fficiencyexocrineproblemsleadingto msleadingto mala absorption,endocrineproblem DM) );recurrentjaundice,stones,maldigestion m

elevatedinserum)

Inherited(trypsinautoinactivation(PRSS1cationictr rypsinogengenegermline mutationincleavagesite,AD,childhoodonset;SPINK1serineproteaseinhibitor Kazaltype1inactivation nmutation,AR) pillarytumor: Pse eudocysts(Nonneoplastic=us suallyunilocular) Solidpseudopap Serouscystadenoma MucinousCystadenoma Intrad ductalpapillarymucinousneo oplasm rls/youngwomen 75% %ofallpancreaticcysts.Walledoffareaof Inadolescentgir Cysts: czones,filled pan ncreaticnecrosishemorrhagic cnecrotictissue solidandcystic Nonneoplastic +en nzymes.Solitary(230cm).On n/in/near w/hemorrhagicdebris,papillary usually heets.B pan ncreas.Walloffibrous+granulationtissue.No projectionsorsh unilocular. epit theliallining.Duetoacutepan ncreatitis(~6wks catenon/APCpathwayaltered. Neoplasticusually Benign glycogen rich low w cuboidal cells Mostly in women. Can be be enign or malig. Arise pos sttrauma)orinthesettingofchronic c ETOH Cystw w/mucus,canbebenignormalig.More multilocular surroundingsmallcystsw/clear w strawcoloredfluid. inbody/tail,painless,slowgr rowing.Contain pan ncreatitis.Sometimesresolveand a disappear, inME EN,headofpancreas. 2Xmoreinwomenin70s s.Nonspecificsx mucin.Lookforinvasiontos seeifmalig mos stcanbeeliminatedbysurgica aldrainage Pancreat ticDuctalAdenocarcinoma Morphology:60 0%ariseinheadofpancreas.20% 2 inentiregland,15%body, 5%tail.Hard,stellategray/wh hitemass(desmoplasticstroma alresponse).Poorly Solidtum mors,ariseinductcells.Progressfromnonneoplasticepitheliumintraepithelialneoplasia(PanIN) defined.Inhead dobstructcommonbileductjaundice).Inbody/tailissillentuntillate.Caninvadeearlyintoextrapancreatictissues,adjacent orinvasiv vecarcinoma.Precursorsepi ithelialtelomereshorteningma aypredisposetoaccumulationof organs/nerves/r regionallymphnodes.Canmet tastasizetoliver,lung,bones. Overall5yrsurvivalis<5%!Fo ormmalignantductstructuresveryHARD(abortive, Pancreatic chromoso omalmutations.Activationofoncogenes(KRASin>90%ofca ases),inactivationoftumorsup ppressor irregular,small). .Anaplasticcuboidalcolumnarcells.Secretemucin.Desmo oplasticStromalresponse.Per rineuralinvasion++.Lymphati icandbloodvessel st Carcinoma genes(p1 1695%,SMAD4BRCA2p53).Accumulationismoreimport tantthantheexactsequence. Cause: invasion.Clinic calfeatures:silent,sxappeartoolate.Painis1 sx(perineur ralinvasionlink).Wtloss,anor rexia,malaise,weakness.Obst tructivejaundice(head). notwellu understood.Age6080yo,M> >F(2:1),Blacks>whites,Jewish hslightrisk.Smoking2Xrisk, r Not Migratorythrom mbophlebitis(Trousseausignof fmalignancy)in10%thrombo osesform,resolve,reappearin ndifferentsitestumorrelease eofnecrotictissue, sureabou utdiet,alcohol,DM,chronicpa ancreatitis.Hereditarypancrea atitis(PRSS1,SPINK1risk50X X).Puetz othersubstance es.Dx:endoscopicultrasound,CTimaging.Tumormarkersca anmonitor(butnotdetect/scre een)diseaseCEA,CA199ag.Prognosis:poor Jehger=>100Xrisk,inheritedcancersy yndromes(BRCA2AshkenaziJews, J p16CDKN2Agene) becauseoflatedx, d <20%areresectableatdx.

Morphology:mildinterstit tialform(BVleakage edema,lipasesperipancreaticfatnecrosis white/yellow,chalky);seve erenecrotizingform (Proteasesparenchyma alnecrosis,BVdestruction hemorrhage).Acuteinflam mmatoryresponsetotissue destructionaddstodamag ge!Cansometimeshave somecalcification/soponif ficationbutitsmoreofan accumulationthanhardca alcifications.

Rx:pancreaticrest(food d,fluidrestriction,supportivet tx).Mostpts s st recoverfully,~5%diein1 wk(shock).Sequelae~50% %get bacterialsuperinfection(G GIGorgs),pseudocystweeks slater,sterile abscess)

Dx:r requiresahighdegreeofsuspicion.During attac ckshaveserumamylase.Gallstone nephosphatase. obst tructioncanleadtohighalkalin on CT/U USshowspancreaticcalcificatio (PAT THOGNOMONIC).Malabsorption(wtloss, hypo oalbuminemicedema). Prog gnosis:50%mortalityover2025 2 yrs;pancreatic insuf fficiency,severechronicpain,10% 1 develop pseu udocyst

DrugsList t
Drug Sulfasalazine Mesalamine Olsalazine Propranolol NonselectiveNSAIDa (Ketorolac) COX2NSAIDs (celecoxib) Bismuthsubsalicyla ate (Peptobismol) Tetracycline Amoxicillin Metronidazole Ciarithromycin Vancomycin Ciprofloxacin Loperamide(Imodium) Diphenoxylate Alosetron Clonidine Nortriptiline Desipramine Amitryptiline Erythromycin Bethanechol Domperidone Metoclopramide Neostigmine Methylnaltrexone Alvimopan Interferon Ribavirin Lamivudine
Antivirals Prokinetics:Someuse espostsurgical ileus,delayedgastricemptying associatedw/diabetic cneuropathies, GERD,functionalcons stipation(IBS) Antidiarrhealdrugs/a antivisceral hypersensitivitydrug gs:Diarrhearesults frompropulsion,enhancedH2O& electrolytesecretion,orboth.Caused byinfectiousagents,inflammatory boweldisease,thyroiddisordersordrug effects.DiarrheaisaSx,notadz. Therefore,treatunde erlyingcause&use thesedrugssparingly AdrenergicAntagonis st(Bblocker sympathetictone) 5ASAderivativemayinhibitIl1/TNF a,inhibitLOX,scaveng gefree radicals/oxidants,inhibitNFkB(but theyarentsure) IBDrem missionusefulnessinCrohnscontroversial,helpfulin UC

Category

MOA/ /USE

PK
Oral O admin,butnotactiveuntildistalGItractbecauseofazoliink(activatedbyGI bacteria)Convertedtosulfapyra adine+5aminosalicylicacid Delayed D releaseformreleasedthrough t smallintestineandcolo on pHsensitiveformreleasedinterminalileum/colon Rapidabsorption,butmostislostinthestool Oral O admin,anASAprodrug(act tiveinlargeintestine,bypasss smallintestine)

SE
N/V V,hepatotoxic,bonemarrows suppression,reversibleoligospe ermia Sulfaallergies Mo orewelltoleratedthansulfasal lazineSErelativelyinfrequent t/minor. Hea adache,dyspepsia,skinrashm mostcommon.Assocw/interstitialnephritis. A s secondgeneration5ASAcrea atedtotrytodiminishSE Dia arrhea,rarelynephrotoxicity Nausea,diarrhea,bronchospasm, ,dyspnea,coldextremities,Ray ynauds exa acerbation,bradycardia,hypote ension,heartfailure,heartblock,fatigue, dizziness,concentration,halluc cinations,insomnia Pep pticulcersw/longtermuse,GIbleeds,uricacidretention,sa aliicylism, oto otoxicity,hepatotoxicity,nephr rotoxicity Can ncausebigGIproblemssincen notselective Car rdiovaculardisease,thromboticevents,profuseGIbleeds,edema,elevated BP, ,allergicrxns.

Canbeusedtopreventbleedingofes sophagealvaricesincirrhosis.Blocksbeta2receptorsof theme esentericarteriolesresultinginunopposedalphavasoconstric ctionreducingbloodflowto mesent terywhichreducesportalHTN. Inhibits sCOX1and2toinhibitPGE2sy ynthesis.Blocksmucussecreti ionstimulatedbyPGs, blocksacidinhibitionbyPGs.Causesacidsecretioningut

Oraladmin,verylipophilic(h highfirstpasseffect)

Oraladmin

Analgesicantiinflamm matories Selectiv velyblockCOX2toinhibitPGsy ynthesisininflammationbutdoesntblockCOX1this meanslesserosionofGImucosa,less sinhibitionofplateletaggregat tion Antibacterial:bindsbacterialtoxins(Bisthmus) Cytoprotectant:coat tsirritatedmucosa Antiinflammatory(su ubsalicylate) Binds30Sribosometo opreventproteinsynthesis Bacteriostatic,Broadspectrum(G+/) Betalactam:Inhibitscross c linkingofpeptidoglycancell c wallbybinding w/penicillinbindingprotein. p Blockstranspeptidases s BreaksdownDNAbyintroducingnitroradicalswhichcausecytotoxic effect(pyruvadeferre edoxinoxidoreductase). Binds50Stoblockpeptidyltransferaseactivityinh hibitstranslocation, bacteriostatic Blockspeptidoglycansynthesistoinhibitcellwallbu uilding 2 genfluoroquinolone:inhibitDNAsynthesisbyinhibiting topoisomerase/gyrase e
nd

Oraladmin

TripletherapyforHpy ylori=(PPI),Metronidazole,AmoxicillinorTetracyc cline,BismuthPleaseMakeTummyBetter)

Usedfordiarrhea,indigestion,abdo ominalcramps UsedforHpylori,vibrio,coxiella,E.histolytica,spirochetes Exten ndedspectrumHpylori,G+/ cocci,G+rods,spirochetes. Usew/anaerobic w bacteria,H.pylori, ,C.Difficile,bactrioides, anaer robicprotozoa,trichomonas(m mosteffectiveforgiardia, entam moeba,trichomonas) Usew/ w Hpylori G+ba acteriaCdifficile. Gba acteria,UTI Suspensionadmin OralorIV.Absorptionblock kedbyfood,milk, Mg/Casalts.Renalexcretion n Oraladmin,widedistribution nexceptCNS(only thereininflammation).Elim mviaactiverenal tubularsecretion. Oraladmin(gelformforrosa acea) Oral,IV Metabolizedviacp450(CIw/ w/statins) IVforinfections(pneumonia a,sepsis) OralforCdiff Oral Poorabsorptionwhentaken nw/antacids DoesntcrossBBB(soabusepotentiallimited) LimitedBBBcrossingHasab busepotentialandcan causeeuporia.Adminw/atr rophinecanreduce potentialforaddiction. Oraladmin,rapidaction,live ermetab Lar rgedosescancausebismuthor rsalicylatetoxicity Bla ackstools/tongue.CancauseR Reyessyndromeinkids. Tee ethstaining/hypoplasiainchild dren,Photosensitivity CIi inpregnantwomenandyoungchildren Alle ergy,neurotoxicityifinflammation,seizures,plateletdyxfx,GI G disturbance, nep phritis Neurotoxicity,nausea,diarrhea,c cystitis,allergy,metallictaste,transient t leu ucopenia/thrombocytopenia, anticoagulanteffectofwarfarin.Has disulfiramlikerxnw/ETOH. Sto omatitis,heartburn,N/D,anore exia,peristalsis(abdominaldiscomfort). d Flushing,nephrotoxic(rare),ototoxic(rare) Art thropathy,damagetojointdev velopmentinchildren,adultten ndinitis,some pro olongedQTintervals,GIupset,convulsions. Cra amps,nausea arrhealatlow Par radoxicalinmotilitybutp propulsions.Iseffectiveantidia dos ses(highercauseeuphoria,abu usepotential) Sev vereconstipation,ischemiccolitisfromfecolithobstruction CI:constipationpredominantIBS, ,IBSw/mixedsx eadache, Hyp potension,drowsiness,constip pation,drymouth,dizziness,he fatigue/weakness,withdrawalsyn ndrome

Muopi ioidreceptoragonistinhibitNO/VIP N releasetoblockrelaxat tionbelowfoodbolus. Nonpropulsive p motilityspastic,uncoordinatedcontractionsresult Antidia arrheal 5HT3re eceptorantagonistpreventssensorynerveactivatedexcitat tion/activationofmotor reflexes.Reducespain/cramping Relieve essxinfemalediarrheapredom minantIBS. CentrallyactingSNSinhibitionbutinwall w ofgut,itisanA2adrenerg gicagonistinhibitsAch release efrommotornervessupplyinggut g mmlayers.Mimicseffectof o sympatheticnn(actsat a2toin nhibitAch,VIPrelease)soitinhibitspropulsivemotilitytoo Hasbeenusedtotxdiarrheapredom minantIBS BlocksNEreuptake,secondaryamine e ATCAusedfordiarrhea,depression n BlocksNE/5HTreuptake,a1/Mantago onist,tertiaryamine ATCAusedfordiarrhea,depression n,fibromyalgia,IBS Macrol lideantibiotic,butalsoaveryselective s potentmotilinrecepto oragonistcauses contrac ctionofsmoothmm,usew/van ncomycinforC.diff. Treatsconstipation Muscar riniccholinergicAch(M3)agon nistonthemmtostimulatecon ntraction Onlyre eallyuseinahospitalsettingwheretryingtotreatpostsurgeryduetoSE. D2anta agonistonperipheralnerves.(leadstoAchreleasefrompr resynterminal).Tightens LESand dfacilitatesgastricemptying.Only O helpsw/upperGItractpro oblems. 5HT4re eceptorsagonist(enhancesAchrelease) Periphe eralD2antagonist(leadsto Achreleasefrompresynterminal).TightensLESand facilitat tesgastricemptying.Alsohelpw/lowerGItractproblems.An ntiemetic. AchEin nhibitortoprolongAchexposuretoreceptorsexcitesthemm mtopromotemotility. GIopia ate(u)receptorantagonist Treatpost p surgicalileus,constipiation n,gastroparesis,beingevaluate edforuseinidiopathic constip pation Inhibitpeptidechaininitiation,stimul latemRNAdegradation,inhibit telongation,induceNKcells Ifna:He epB/C,posttransplantCMV,ge enitalwarts,tumors Ifnb:MS M Nucleo osideantimetaboliteguanosin neanalogthatinhibitssynthesisofGTP,viralmRNA HepC,usew/pegylatedIfn,RSV NRTI(n nucleosideRTinhibitor)termi inatesDNAchainelongation HepB,HIV

Oralortransdermal

Oral.SometolerancetoSE, ECGrequiredprior to/duringtx.Overdosedang ger.

rinaryretention, Car rdiacdysrhythmiasw/overdose e,drymouth,blurredvision,ur con nstipation,sedation,wtgain,orthostatichypotension/dizziness,sexualdysfx. sarebeing Con ncernsaboutdevelopingantibioticresistancethemotilides eeffect,no cre eatedasanalogstoerythromyc cintosolvethisproblemsame ant tibacterialactivity.Cramps,dia arrhea HR,blurredvision,constrictedbronchioles ho ot as a hare, blind as a bat, d dry as a bone, red as a beet, and mad as a hat tter NotapprovedinUSA.DoesntcauseParkinsonianlikesyndromesfromD2 ant tagonistactionbecauseitdoes sntgettobrain. Par rkinsonianlikesyndromesfrom mD2antagonistaction(EPSsideeffects) Hyp perprolactinemia>amenorrhea a,galactorrhea Agi itation,insomnia,anxiety,drow wsiness onlikeSElisted Hyp potensionmanycholinergicS SE(diarrhea,salivation,urinatio for rbethanecol) Can ncauseN/V,buttolerancedev velopsovertime. mia,liver Thr rombocytopenia,bonemarrow wsuppression,leucopenia/anem enz zymes,CNStoxicity(depression n,lunginfiltrates,flulike,autoimmune, alo opecia Red ducedrbcfromhemolysis,mye elosuppression CIi inpregnancyteratogenic Hepatotoxic,resistancein1yr(20 0%),headache,nausea,pancreatitis(kids),80% hav verecurrencew/discontinuatio onofdrug

Oraladmin Canadministerparenterally,,butuseorallyto avoidCV/respiratorycomplic cations LimitedBBBpermeability PermeatesBBB Usuallyusepostsurgicallyd uetoSE DoesntcrossBBB.Doesntb blockanalgesiceffects likeNaloxonewould.Canus setotreat constipationanawfulSEas ssociatedwithopiate use.24hrrelief. 1/wkinjection Oraladmin Oraladmin

DrugsList,Continued
Drug Pancrease
Category
Pancreaticreplacement

MOA/USE
Helpsdigestproteins,starches,fats.Containslipase,amylase,protease(trypsin). Useinexocrinepancreaticinsufficiency,CF,chronicpancreatitis,blockedbileduct, steatorrhea

PK
Entericformcoatedforreplacement(sonotbrokendownby gastricacid)mayneedtouseH2blockeraswelltoallowit nottobreakdown

SE
Hyperuricemia(gout),hyperuricosuria,allergicrxns,GIupset

Somatostatin (octreotide) CaCO3(Tums) Al(OH)3 Mg(OH)2(milkof magnesia) NaHCO3 Bifidobacterium infantis VSL#3 Lectobacilus plantarum Meperidine

NeurotransmitterReleaseinhibitor pancreaticsecretions(bigtimeinhibitorydrug)InhibitsgastrinreleasefromGcellsinantrum,inhibitsCCKsecretion,inhibits H+productionbyparietalcells,inhibitshistaminereleasefromECLcells.Inhibitssecretionofpituitary/pancreatichormones, GIhormonesecretionandGH/IGF1secretion;inhibits5HTreleaseforsxreliefofcarcinoidtumors. Canbeusedtotreatesophagealhemorrhagesinhibitsvasodilatorymediatorstocausevasoconstrictionofmesentericblood vesselstherebyreducingbloodflowandportalpressures. Antacid:Chemicallyneutralize stomachacidraiseGIpHtorelieve painofdyspepsia,acidindigestion, enablepepticulcerstoheal.Mostly hydroxidebasesassociatedw/various cations Allcausehypokalemia Probioticagents:seemtosuppress systemicinflammation,feelingsof bloating,andimprovemild diarrhea/constipationasassociated withlowlevelentericinfection CaCO3+2HClCaCl2+H2O Al(OH)3+HClAlCl3+3H2O Mg(OH)2+HClMgCl2+2H20 Neutralizesacid,pepsidinhibitionfrompH(sameasallothersabove,Ijustdont knowthechem.equation)

SCorIMadmin

Nausea,cramping,diarrhea,vomiting,fatty/loosestools,cholethiasis,HA, dizziness,fatigue,hyper/hypoglycemia,hypothyroidism,galactorrhea,flushing. RecommendedtomonitorVitaminB12. Becarefulwithalloftheseifpthaskidneyproblems(hardforthemtopassthe ions)otherwiseprettysafeshortterm.Hypercalcemia,reboundacid Constipation,alluminimumamountoffeces,hypophosphatemia,proximal mmweakness,osteodystrophy,seizures ProducesdiarrheaagoodlaxativeMg=MustGotothebathroom. Hyporeflexia,hypotension,cardiacarrest Metabolicalkalosis

Shortduration,fastonset.Canchelate,effectivenessof otherdrugs(liketetracycline) Longduration,slowonset Shortduration,moderateonset Shortduration,fastonset

Mechanismnotreallyunderstooddothebacteriaoutcompeteinfectious pathogen?Dotheysubduethereleaseofinflammatoryfactors?Wearentsure.

Oral

Nonethattheyreallytalkedabout

NarcoticAnalgesia

Opioidagonist(mu,kappa) Painmed. Dareceptorantagonist(phenothiazine)bindD2receptor(andD1,a1,M1,H1). Antipsychotic,centralstimulantblocking,antiemeticbyinhibitingNSTandCTZ Usedforchemoassocemesis,palliativeforschizo,mania

Oraladmin,urineelim CrossesBBB(addictivepotential) Givenaloxene(opiumreceptorantagonist)tocounter overdose

Tremor,seizures.Cautioninrenalfailurebuildupofmetabolite normeperidinecancauseseizures.Drymouth,sorethroat,constipation. MildextrapyramidalSE(canreversew/muscarinicantaglikebenztropine) dystonias,tardivedyskinesia,parkinsonism,sedation,hypotension, hyperprolactinemia,neurolepticmaligsyndrome(rareemotionaldetachment, affectiveindifference),sexualdysfx. QTprolongedw/droperidol,EPS(high),sedation/hypotension, hyperprolactinemia,sexualdysfx.Tolerancetosedation/hypotensiondevelops, nodependenceorabusepotential,highpotency Agitation,insomnia,anxiety,drowsiness,EPS,hyperprolactinemia>amenorrhea, galactorrhea.Stimulatessmallandlargeintestinemotility. Relativelysafe,fewSEconstipation(occasional),HA,lightheadedness, prolongedQT(minor)

Chlorpromazine Droperidol Haloperidol Metoclopramide Ondansetron Dolasetron Granisetron Dronebinol Sucralfate

Cytoprotectants:PGsinhibitacid secretionandstimulatebicarb/mucous secretion.Neededtoprotectthe stomachwhenPGsarebrokendown (NSAIDs,etc) Antiemeticdrugs:workinCNSat vomitingcenter(areapostrema,NTS, CTZ).Canbeusedtotxchemotx inducedemesis(acutein24hrsdrugs mosteffectivehere,delayeddrugs notaseffective,anticipatoryless severewhenacuteemesisistreated effectively).

OralorIM(highlylipophilic)

D2antagonistantiemeticbyinhibitingNSTandCTZ Usedforchemoassocemesis,schizo,mania(bipolar) Da/5HT3antagonist,weak5HT4agonistforAchrelease.WorksinCTZ/NSTas antiemetic,GImotility Usedforchemoassocemesis,GERD,postsurgileus 5HT3receptorantagonistonafferentnerveendingsinGImucosa,central5HT blockinNST/CTZ UsedforchemoassocemesisYouwontvomitsoyoucangoONDANSing SyntheticmarijuanaactsatCB1receptorssuppressesneuronsinarea postrema.Alsostimulatesappetite. Intheacidicenvironmentofthestomachbecomesnegativelychargedandturns intoaviscousgelformingaprotectivebarriertopromotehealing.Notreallyused atonnow,maybeinburnpts.Thinkofitlikeachemicalbandaidthatallows ulcertoheal.UsedforulcersnotcausedbyNSAIDuse.Helppreventrecurrence. AstablePGE1analogusedtotxpepticulcerdisease,especiallythatassociated w/useofNSAIDs.ActsonEP3receptortostimulatebicarb/mucoussecretion, cAMP/inhibitsacidsecretioninparietalcells,mucosalbloodflow UsedtopreventNSAIDinducedulceration,maintainpatentductusarteriosus, inducelabor Cataboliceffectinducesnewproteinsynthesis,GNG,lipolysis,peripheral glucoseuse.Antiinflammatory,immunosuppressant Hasaffinityforglucocorticoidreceptor50100Xgreaterthanprednisone Unknownmechproposedtoimprovehealthandrecoveryfromillnessandtxof HepC.Aphrodesiac,improveenergy,reducestress,improvementalperformance. Evidencedoesntsupportclaims.Maybeusefulindiabeticstocontrolblood sugars Oral Interactsw/phenelzineHA InducescytP450!!!Preparationsnotstandardized Interactsw/alotofmedsdigoxin,oralcontraceptives, warfarin,indinavir,loperimide,omeprazole, Oral IVinfusion SCinjection

CanbeoralorIV Livermetab MakesareallysickpatientfeelaLOTbetter Difficulttousehavetowaitforulcertohealbeforeyouuse anyacidsuppressiondrugs(sinceitneedsacidtowork) Locallyacting,shorthalflife

Constipation,assocw/bezoarformation

Misoprostol Prednisone Budesonide Ginseng St.Johnswort MilkThistle (Silymanin) Infliximab

ShortT

Diarrhea,cramping,menstrualirregularities, CIinpregnancy!Abortioninpregnantwomen.

Glucocorticoids:IBD(bothCrohnsand UC)oftenabletoinduceremissionbut lessvaluableinmaintainingremission, especiallywithoutcausingtoxicity

Oral

SE:Osteoporosis,Cushingoidrxn,Psychosis,Glucoseintolerance, Infection,HTN,Cataracts,longtermusehasnomaintenancebenefit

Headache,GIupset,hypoglycemia,sleepdisturbances

Herbalproducts

Usedformilddepression.Hypericinisactiveingredient.EffectsequaltoTCAsin someclinicalstudies,lowgradeevidenceforotherbenefits GradeBevidencefortxofchronichepatitisorcirrhosis(alcoholicorotherwise), andgallbladder.Moststudiesshowedimprovementinliverfxtestsovertime. Antidotefordeathcapmushroom(amanitaphalloides) TNFamonoclonalab. UsefulbecauseTNFaisexpressedinCrohns,alsousedinRA TNFamonoclonalab,DMARD UsefulbecauseTNFaisexpressedinCrohns(alsousedinjuvenileRA,ankylosing spondylitis)

SimilartoSSRIs:Photosensitivity,drymouth,dizziness,majorGIupset,Di w/cP450 Cautioninptsw/diabetesorhypoglycemiamayactasphytoestrogenand shouldbeavoidedbypregnantwomenandptsw/hormonesensitivecancers. Laxativeeffect,upsetstomach,diarrhea,bloating,allergicrxns Fever,chills,fatigue,hypersensitivity,riskofinfections/malignancies ShouldobtainaTBtestbeforestartingtx(canallowreactivationtb)

Monoclonalabs

Adalimumab(Humira)

DrugsList t,Continued d
Drug Omeprazole Lansoprazole Pantoprazole Rabeprazole 6Mercaptopurine Azathioprine
Immunosuppressants s

Category

MOA/ /USE
H/KAT TPaseformscovalentbondwith hactiveformofdrugthatcomp pletely inactiva atesthedrug.Irreversiblyinac ctivatesH/KATPasechannelandnewones haveto obecreatedbeforetheirfxreturnsforacidsecretion Use:pe epticulcer,gastritis,esophagea alreflux,ZES PurineanaloginhibitDNA/RNAsynt thesisbyinhibitingfirststepindenovopurine synthesis,metabolizedbyxanthineox xidase UseALL, A CML,IBD Metabo olizedto6mercaptopurine(so osamemech).UseIBD

PK
Inactiveun ntilithitsacidicenvironmento ofthestomach sulfonylgr rouposcillatesbetweensulfona amideandsulfenic acid.Sulfe enicacidisactiveformofdrug..Verypowerful,only 1doseper rdayisneeded

SE
Virt tuallyfreeofSE(onlyactivated dinstomach).Stateoftheartfortxofulcers, etc c.CanhaveMMC.B12ab bsorption,bacterialgrowth

Protonpumpinhibito ors:

DI:Allopur rinol(whichinhibitsxanthineo oxidase,lowerby75% orelsesee etoxicities)

Hepatotoxicityjaundice,bonem marrowsuppression,immunosu uppression,GI dist turbances

Methotrexate Cyclosporine Bran Psyllium Methylcellulose Bisacodyl Anthraquinones Magnesiumcitrateor sulfate Lactulose Lubiprostone Spironolactone Cimetidine Ranitidine Nizatidine Famoticine Nacetylcysteine
Liverprotectants

Folicacid a antagonistblockTHF FsynthesisbyinhibitingDH HFR,lackof THFin nterferesw/dTMPanddenovo n synthesisdiminishDNA D replica ationinSphase UseA ALL,AML,NHL,choriocarcinoma,osteosarcoma,RA,IBD
Calcine eurininhibitorblockslymphoc cyteactivation nd UseCrohns C disease(2 line) Bulkfo ormingwhenabolusgetsinto ocolon,itabsorbswater,disten ndsthecolon, activatespolarizedreflexestostimula ateperistalsis.

Accumulat tesinfluid Weeklying gestion(IMorSC),Takessevera ralweeks. Renalelim m Addedafte erinitial710daysofIVhighdo osecorticosteroids 13daysto oeffect.Usedasanadjunctto odietary/behavioral changes,acute a txafteranalrectalsurger ry

Mo outhulcers,GItoxicity,hepatot toxicity,nephrotoxicity,alopecia,bonemarrow sup ppression.Cautioninedemaan ndrenalfailurecanaccumulatedoses. Leu ucovorinusedtorescuenormalcellsinbonemarrow. Nephrotoxic,hyperkalemia,HTN,gingivalhyperplasia

Laxatives:constipatio oncanresultfrom adisruptionofnorma al absorptive/secretorybalanceand/or alteredmotility,abuseoflaxatives. Besttotxunderlyingcause.Useprior tocolonoscopy.

Obstructionifyoudontproperlyhydrate Stimula antdirectlystimulatecAMPforwater/electrolytesecretion getsemi fluidstools.Widelyusedandsometim mesabusedbypts.Butoktouse u for occasio onalconstipation. Salineosmotic.Waterevacuation(SE EVERE)souseisreallylimited d.Usedto preparebowelforcolonoscopy(clean nitoutcompletely)resultisEXPLOSIVE 68hoursto t effect.Semifluidstools

13hoursto t effect

Fluid/electrolytedepletion

Helpsopen o ClC2tosecreteCl.Watermovesintolumenusedtotreat t chronic constip pation K+sparingdiuretic,AldosteroneantagonistatDCT,Used U fordieresis Canbeusedw/furosimidetotreatascites H2Antagonists:block kH2receptorsonparietalcellsashistaminefacilitatesH+se ecretion causedbyothersecre etagogues,H2blockersareeffe ectiveinreducingH+secretionin responsetoanysecre etagogue.H2antagonistsareused u initiallyforthepharmacologicaltx ofgastroduodenalulcersandGERD(inexpensive).UseofH2blockersshouldbe accompaniedbylifest tylechanges. Theleastpotentof o H2blockers Morepotentthan nCimetidine, butwithfewerSE.Allavailable OTC.

Oral AvoidK+supplements,dontuseinrenallfailure. Longerhalflivesthancimetidine

Noproblemsw/tolerance,dependency,orelectrolyteimbalance Hyp perkalemia,gynecomastia,imp potence,GIdisturbances,metabolicacidosis, loselotsofNa/waterinurine Ant tiandrogenic(gynecomastia)+alllistedbelow enal P45 50inhibition.Diarrhea,headac ches.Needtoreducedoseifre insufficiency.

Sadenosyl methionine

AcetominophenusesupGSHalcoholmakesthisworse. w ThisdrugGSHandbin ndstoxins, preventsliverdamage e. Txforacetaminophen noverdosew/prompttx Glutathioneprecursorprovidesprotectiontooxida ativestress.SAMisreducedin nalcoholicliver disease.WeakandinconsistentevidencehintsthatSAMemightbehelpfulforava arietyofliver conditionssuchascirrhosis,chronicviralhepatitis,pregnancy p relatedjaundice,andGilbert's syndrome.Thebodymakes m alltheSAMeitneeds,so othereisnodietaryrequireme ent.However, deficienciesinmethio onine,folate,orvitaminB12can nreduceSAMelevels.SAMeisnotfoundin appreciablequantitiesinfoods,soitmustbetakenas a asupplement.

IVadmin

N/V V,anaphylacticrxn.

Oralsupplement

e,hives,stomach Ser riousallergicrxnclosedthroa at,swellingoflips,tongue,face ach hne,nausea,diarrhea,gas,anxiety,spasms,insomnia CIi ifpregnantorbreastfeeding

DrugDrugInteractions s,metab te,renalfx,hepaticfx,seru umproteinconc,food, Ptfactors:diseasestat env,useofalcohol/tob bacco,genetics,age,gende er Riskfactors:drugsw/n narrowtherapeuticindices s(doseresponsecurve shiftedleft),administr rationoflarge#ofdrugs,criticalillness,HIV infection,substanceab buse CYP450interactions: Phase1metab( (addgrouptocompoundoxidations, reductions,hydr rolysis)CYPsdooxidation nreaction(alsoFMOs, MAOs,XO,etc). o ReactionofCYP450:Drug+2NADPH H+O2DrugOH+ NADP++H2O CY YP450s:afamilyofenzyme esthatoxidizedrugs. M Manyisoformsexist.Inmosthumans,catalyzed by yCYP3A,CYP2D6,CYP2C,CYP1A2, C CYP2E1. M Manydrugdruginteractionsthrough in nhibition/induction.Altere edhepaticbloodflow ca anaffectdrugmetabol(pro opranolol) Ca anmakedrugsmoreorles sstoxic(dependingon th hepathwayandwhatthemetabolites m are) Ex xofinducers:Phenobarbital,carbamazepine, Ci igarettes,ETOH,phenytoin n,Rifampin In nhibitors:Allopurinol,cimetidine,ciprofloxacin, clarithromycinetc o Grapefrui itjuiceinhibitshepaticand dintestinalCYPs responsib blefor1stpassmetabofsomedrugs(dueto furanocou umarineslikebergamottin)getCmaxand AUC.Can nalsoinhibitorganicaniontransporting polypeptide,Pglycoproteintranspo ortofdrugsinGI epithel.(exfelodipine,cyclosporine,tacrolimus,statins, e,carbamezepine,diazepam,midazolam, buspirone triazolam, ,methadone,sildenafil,nif fedipine) o Phase2:conjuga ationsw/glutathione,glucuronicacid,sulfate, acetate,methyl, ,etc y Ethanolmetab/toxicity Rapidlyabsorbe ed. Liverisorganof f1stpass.

Eliminatedviameta ab:ETOHacetaldehyde acetate(Krebbscycle) c H20+CO2 Alcoholdehydrogen nases: o HumanADHiscytosolic,containsZn.20 2 dedin5genes,allprettysm mall. isozymescod Lotsofpolym morphisms(leadtodifferen nces amongindividuals) o ETOHlosesanelectrontoNAD:ETOH+ NAD+Acetetaldehyde+NADH.Canget excessNADH(shiftinglactate/pyruvateratio) MEOS(microsomalethanoloxidizingsystem)= CYP2E1residesinSER,requiresO2+NADPH H, producesacetaldeh hyde,NADP,andH2O.Only doesabout10%ofalcoholmetab Catalase:inperoxisomes:ETOH+H2O2 acetaldehyde+H2O O(probablycontributesvery little)

Alcoholblooddi isappearanceiszeroorder r.Fastingalcohol dehydrogenase. eandfreqofconsumption n. Adverseeffectsofethanoldependondose etaldehydeconc,steatosis s, Effectsonliver:NADH/NADratio,ace proteinexport,produ uctionofcoagfactors, proteinaccum, watercontent, watercontent,oxyge enuptake(centrilobular hypoxia),prolife erationofER(CYPconce entration,ordrug metab),product tionoffreeradicalsandlip pidperoxidation,collage en deposition(scarring,cirrhosis),hepatitis,c celldeath Extrahepaticeffe ects:GI(gastritis,pepticullcer),pancreatitis,heart (vasodilation,ca ardiomyopathy,arrhythmia as),portalHTN,endocrine (feminization),cancer c (upperGI,liver),fet talalcoholsyndrome,acute e depressant,chro onicWKsyndrome,imm munecompromise

Ethanoldruginteractionexample: Expectexce esssedation(interactw/se edative hypnotics,a antidepressants,neurolept tics,sedating antihistamines,narcotics) Interferesw w/metab(inhibitscertainCYPs, C induces others)in nterferesw/warfarin,hypoglycemic sulfonylureas,acetaminophen,others s Somedrugs scauseaccumofacetaldeh hydefrom ETOHmetab(metronidazole,sulfonyl lureas, n,cephalosporins,chloramphenicol) griseofulvin CanriskofGIbleedfromNSAIDs

e inmetabolizing Acetaldehydeoxidation:efficient acetaldehyde.2classeslowKmALDH2(in mitochondria,doesmostmetab),highKmALDHs1/ /3/4 (incytosol) Inhibitors:disulfura am,daidzin(unpleasantrxn nof periphvasodilation,sweating,headache,naus sea, vomiting) 50%ofAsianshaveinactivegeneticvariantof f etab,lowincidenceof ALDH2slowerme alcoholism

(acetaminophen=APAPinthisslide). Overtime,depletionofglutathionecausesNAPQI N build upbindstothingslikeproteinsinliverfo orm macromoleculest thatcanleadtonecrosis. dbyETOH:competitiveinh hibitionor CYP2E1isaffected inductionCYP2E1canoccurwhenethanolistakenin, getmoreproteinfor2E1 ss

BugsList
Mouth:heavilycolo onized,variesfromsitetositeAlpha Esophag gus:mostly Smallintestine:moreanaero obic Largeintestine:9095anaerobes.Feces byweightis Stomach:ster rileifacidpromotesenzymes.OccasionallyseeG+sthat streptococci,Streptococcusmutans,Neisseriasp,Diptheroids,S. transien ntsfrom environment.Floraisscarce, ,with 20%bacte eria.IncludesBifidobacterium,Eubacterium, areacidresist tant(Streptococcus,Staphyloco occus,Lactobacillus, aureus,S.epidermid dis,Lactobacilli,spirochetes,Mycoplasma;Lots mouthand a URT distancefromstomach.Mos stlyanaerobes Bacteroide es,Fusobacterium,Clostridium,Lactobacillus, peptostreptoc coccus,fusobacterium,helicob bacter). ofanaerobes:bacteroides,fusobacterium,clostridium, (veryfew worganisms (Enterococci,peptostreptoco occi, Streptococ cci,Enterococci(upto1%),Enterobacteriaceae 10^310^5 1 pergramofcontents peptostreptococcus ingener ral) Porphyromonas,Prevotella) (0.1%).10 0^1110^12pergram!Lots! RolesofGIFlora: Diarrhe ea:aninstoolmass,freque ency,and/orfluidityruns excludingexogenouspathogenscoloniza ationresistance(occupiesadh hesionsites,alters Dysent tery:painful,frequent,smallvo olumestoolsw/fecalleukocyte es(andblood)commonlycau usedbyShigelladysenteriae squirts physicochem micalenvironment,produceant tagonisticsubstanceslikebacte eriocins,useup Nonin nflammatorysecretory:viaenterotoxinand/oradherence/su uperficialinvasioninproximalsmallbowel.Causeswaterydia arrhea.NOFECALLEUKOCYTES S.Exfood availablenut trients), poisoningviapreformedtoxin,waterydiarrheafromproxsmallint testine(Vibriocholerae). developingim mmunefx(numberoflymph hocytesandplasmacellsinlam minapropria,size Foodpoisoning:group,acuteN/V,timeofonsetveryshort( (14hrs,preformedtoxin)ma ajoragentsareBaciluscereus,Staphaureus ofPeyerspa atches,mesentericlymphnode es,spleen,thymus,m Waterydiarrhealargevolum mesricewaterstools,oftend duetoproductionoftoxinsthat taffectsecretion/absorptionin nsmallintestinestarts13da ayspostinfection chemotactic/ /phagocyticactivity,productionofIgGandIgA), andlastsseveraldays(cholera a) developing/d differentiatingmucosalepithelium, Rotavirus:Youngpt,3dayhx,nooneelseinfamilyhassx,po otentiallyexposedtoanothers sickchild developingnutritional n capabilities,providin ngnutrients, Norovirus,:2dayslateracut teN/V/diarrhearelatedtoGRO OUPeatingFOOD.Nopus/RBC Cs,lasts12days. providingvitamins:K(bacteroides,prorpionobac,enterococci,enterobac) ),Folicacid Exudat tive(inflammatory)diarrhea:via v invasion/cytotoxin,inflamm matoryresponsetriggeredinco olonleadingtodysentery/inflam mmatorydiarrhea.Stoolexamhasfecal (bifidobacter rium,enterococci,Ecoli),B12(E ( coli,bifidobacterium,klebsie ella,clostridium, leukocy ytes,sometimesRBCs(exshigella,EHEC,Salmonellaenterid ditis,Campylobacter).Leukocy ytesinstoolindicateinvasivepathogen(butlackdoesntruleitout) fusobac),B2(Ecoli,citrobacter,Klebsiella),Biotin(Ecoli,bifidobacterium),Thiamine Dysentery(shigella,EIEC,EHEC C,campylobacter,somesalmo onella):Pus/blood,eatingtoget ther.AcuteN/V,SEVEREabdom minalpain,frequent/smallvolu umediarrhea (bifidobacter rium),Nicotinicacid(bifidobact terium),Pyridoxine(Bifidobact terium) w/pus/blood,canlastseveralday detoxofmat terials Shigella:Daycare,spreadseas silytoothers(group),pus/blood d,fever,tenesmus,slowlyprog gressing(3days) Disruptionofnorma alGImicrobiota:susceptibilitytoentericdisease,antibioticassocdiarrhea, Giardia:Wtlossover2months,greasystoolsmostlyafterm meals,35waterystoolsdaily,hxofmountainstreams andpseudomembra anouscolitisfromCdiff.Canch hangeentirepopulationofgutmicrofloraand C.diff:45y/owoman,nosoco omial,dischargedw/maintenan nceantibioticsafterelectivesurgery,nooneelseshowssx thatisseenafter2weeks w System micDisease(entericfever):organismpenetratesthebloodsys ystemfromtheGItract.Startsinsmallbowelbutspreadstot thewholebody(exSalmonellatyphi,Yersinia Jejunum:absorbs35Lwater/day,iliumabsorbs24L/day,colonabsorbs12L/ /day(canabsorb enterocolitica).Sx:N/V,abdominalpa ain,diarrhea/dysentery,fever( (happenespeciallyw/orgthatcausecolitis,lowerinGItract) 6).Inseverediarrhe ea,canlose14L+ofwater.

Normalfloraofth he GItract

Organism
EscherichiacoliETEC C (enterotoxigenic)

Staining/Dx

Virulence
Fimbriaeconveyspecificity:K99strainspathogenicforcalves,lambs,pigs;K88strains C CS(colisurfaceag) pathogenicforpigsonly;HumanETEChasCFA, Exotoxins: LT(labileto oxinlikecholeratoxinADP A ribosyltransferasetha attargetsGsandleadsto elevatedcA AMPlevelsinintestinalepithelialcellswaterydiar rrhea), ST(stabletoxin t smallpeptidetoxinthatbindsguanylatecycla aseandcausescGMP sameneteffects e asLT) Toxingene esareencodedonaplasma a(oftensameasCFA) Intiminadhesion, ,T3SS,Tir ShigatoxinsStx1/ /2;Hemolysins Often0157:H7,but b otherserotypesalsoseen. Doesntinvadeattachtoepithelium,insm mallbowel Bundleformingpili, p Intimin,Type3SecretionSysteminjectstoxinsin ntohostcells,Tir(abacteri ial proteintranslocatedintoepithelialcellsbyatypeIIIsecretionsystem m) xins Noknownexotox EPECadhesion:Microcolony M formationbyBfp B (step1).Thenintimate eattachmentbyOMP receptorbindingmediatedbyOMP(intim min)andreceptor(Tir).Bac cteriaattachtoenterocyte e tothereffects,disruptthe ehostcellapicalcytoskelet tonandformpedestals membrane,inject Invplasmidmobilegeneticelement

ClinicalPresent tation
Hypersecretionin smallintestine. AdheresviaCFAp pili,butnoninvasive,noinflammation Travelersdiarrhea a(watery) Attaching/Effacing glesionsinlargeintestineformationofpedestalun nder bacteria,lossoflo ocalmicrovilliandelongationofremainingmicrovillileadsto lossofabsorptive capability. Hemorrhagiccolit tis.Bloodydiarrhea,HUS.Stool:RBCs Attaching/Effacing glesionsinsmallintestine (formpedestalunderbact teria,lose localmicrovili,rem mainingmicrovillielongate e) Causeswaterydia arrheaininfants,sometrav vellersdiarrhea.Diarrhea adueto damagetohostce ellsanddisruptionofabsorption Tx:Usuallyselflim mitingfluoroquinolones,bacim

Epi
Endemicinsome s areas 600millioncases c worldwideannually(800 thousandde eathsin children<5yrs) y Lowinnocula ativedose Undercookedbeef,milk, es fruits,veggie Infants Food/water on contaminatio Children<5 RareinUS T:Oralfecal(food) Humanreservoir

LargeGramnegrod r Fermentslactose e TSI:yellow/yellow w MAC:pink HE:Orange(FLac/Suc) CNA:nogrowth Oxidaseneg Indole:pink(+)

EscherichiacoliEHEC C (Enterohemorrhagic)

EscherichiacoliEPEC C (Enteropathogenic)

EschericiacoliEIEC (Enteroinvasive) EscherichiacoliEagg gEC (Enteroaggregative) Salmonellaenteric gastroenteritis

Salmonellaenteric serotypeTyphityphoid fever

Grod, Motile Fermentglucose, , Oxidaseneg, Doesntferment lactose(clearon Mac), H2S+

Invasiveincolon mucosalinvasion,localsp pread(likeShigella) WateryDysent tery,inflammatorydiarrhea(gastroenteritis) Tx:Usuallyselflim mitingusefluoroquinolon nes,bactrim Stool:RBCsandP PMNs Bundleformingpili p Formsadherentb biofilminsmallintestine Hemolysin,ST,Ch holeraliketoxin(ST). Mucoidwaterydia arrheainchildren(2wks),prolongedinAIDSpts. Noknownexotox xins Gastroenteritisinv volvingsmallbowel(diarrh hea,nauseaw/fecalleuko ocytes) LPS(Oagrepeats s)causesfever Duetodirec ctdamagetoenterocytes/ /inflammatoryresponse TypeIIIsecretionsystems,invasinproteins(invAHgenes,others) 12dayslat terabdominalpain,N/V/ /Dfor34days Entryviatriggerandmembraneruffling(enterMcellsofsmallintes stineusingT3SStoinduce Somecause ecolitis(dysenteryw/pmnsandbloodinstool) ngandformationofphagosome,injecteffectorsthat tmodifyphagosomeso Salmonellosis:No ontyphoidalorganismsten ndtocauseonlylocalized membranerufflin bacteriacanmult tiplywithin).Liketomultip plyinPeyerpatches.Exoc cytoseintolaminapropria inflammatoryresp ponseindistalileumandcolon.Gastroenteritisdiarrhea. (thereT3SSfacilit tatessurvivalinms/killing).Stimulateslocalinflam mmatoryresponse.Disease e Bluntvilli,vascula rcongestion,inflammatio on(watery) duetoenterocyte esandinflammatoryrespo onsesmorethantoxins. Tx:Onlytxw/antib bioticsifothercompromis singillnesses(usuallydont Acidenvironmen ntofstomachturnsonexp pressionofvirulencegenes. recommendtxbec causecarrierstate).Sto ool:PMN+ Capcularags(Viags) a stopsPMNphagocyt tosis Systemicinfectionentericfever r(pain,diarrhea,dysentery y,bacteremia,extraintestinalinfectionslow,lastsf for Noknownexotox xins weeks). .Rosespotsonabdomenandchestblanchonpressu ure.Constipationthendia arrhea(chronicinfectionofblood LPScausesfever stream, ,encephalopathy,infection natbiliarytree).Chronicc carriersmaygetgallbladde erinfection. TypeIIIsecretiontoinjectproteinsfrombacteriainto Typhoid dfever: cytoplasm a gastroenteritisform(see eabove) Wk W 1:bacteremia,fever,ch hills Multipliessameas Genesinducedby ylowO2tensionofgut.May M beinduced Wk W 2:mononuclearphagoc cytesrash,abdominalp pain,prostration byacidpHinstom mach Wk W 3:ulcerationofPeyerspatches,intestinalbleedin ng,shock.Cantraveltomesentericlymphnodesand dms Passthroughinte estinalepithelialcellsviatr ranscytosis candisseminateinfectionbody b widebacteremia,sy ystemic w/minimalepithe elialdamage,enterlaminapropria(5 Stool:monocytes m 10%leadtobacte eremia) Tx:fluid d,electrolytes;canusechloramphenicol,ampicillin,,cephalosporins,quinalon nes

eggs R:animals,poultry, p atedfood T:contamina cookedmeat, (raw/underc y,milk),water. eggs,poultry Need>10^6cfu.

anpathogen Strictlyhuma Tropical(LatinAmerica, Asia,India),developing food U countries.Usually borne T:Oralfecal

BugsList,continued
Shigellaspp(S. dysenteriae,S.sonnei i,S. flexneri) Grod Facultativeanaer robe Nonmotile Acidresistant Doesntferment lactose(clearon MAC) Closelyrelatedto o EIEC Hektoenagar Attachtolargein ntestineMcells,triggerupt takeviareceptormediated dendocytosis(membrane ruffling)mediated dbyTypeIIIsecretionsyst temandIpaproteins(IpaA ABCD)encodedonlarge22 20 Kbinvasionplasm mid.Rapidly(<15min)esca apephagosomeintohostcell c cytoplasm(IpaB/C/D requiredformpores p inphagosomememb brane).Onceincytoplasm,bacteriamultiply,spreadto otherepithelialcellsviaIcsABintracellularspread.Polymerizeshostcellactinatonepoleofce ell romcelltocellthroughhos st andmovesthroughcytoplasmonactintails.Canspreadlaterallyfr epithelium,andcan c movethroughepithelia allayertolaminapropria,where w theytriggerastrong inflammatoryres sponse LPS,Shigatoxin(v verotoxinnotnecessaryfo ordisease,butcontributestoseverity) Similartoxins(Stx x1/2)inEHEC. ABsubunittoxin Bsubunitbinds b Gb3globotriaosylceramidesonrenaltubularce ell,vascularcellson kidney/bra ain/intestine,Pnethcellsinintestine. Asubunitisofthelargesubunitofho ostcellribosome,irreversiblydestroyingribosomalfx x, roteinsynthesis(leadstocell c death.Damagescapilla aryendothelium blockingpr (microthro ombiincolonandkidneyHUShemolyticanemia) enetratemucus. LPS,flagellatope ndocyticvacuoles,thenass sociatesw/cell Enterscellsviaen microtubulenetw work. sionbutcytoplasm Cytolethaldistendingtoxinarrestscelldivis continuestogrow w Intestinalepithelia alcellskilledbyintracellula ar multiplicationofb bacteria,shigatoxineffects s inflammatoryresp ponsesurfaceerosions/ /ulcersin gutwall,acuteinf flammatorycolitis,bloody dysentery.Usually yinfectionsarelimitedtothe intestinalmucosallepitheliumandsubmucos sa.Onset st afewdays.1 w waterydiarrhea,thenbloo ody(50%) causeshemorrh agiccolitislikeIBD Shigatoxininkidne eyscanHUS(alsoseeni inEHEC) Tx:generallyself limiting,butdehydrationc canbea severeproblem.H Hydration,fluoroquinolone es, bactrim(ifsuscept tible) Stool:rbcs,pmns R:Stricthum manpathogenNEVERco onsidered normalflora a. T:Oralfecal,especiallyinunderdeveloped countries;m mostlyinyoungchildrenof fdeveloped. Outbreaksi indaycarecenters,mentalinstitutions, cruiseships s. Highlyinfec ctions(<200canleadtodis sease)because veryacidre esistant. ~25,000cas sesreported/yrinUS.>1/2 2inchildren <5yrsold. Preventionsanitationnoeffectivevaccineyet althoughliv veattenuatedvaccinesund der investigation. T:Lowinfect tivedose (<1000cfu) R:GItractsof o animals, uncookedpo oultry onbacterial Mostcommo causeofdiar rrheain developedcountries

Campylobacterjejuni

Grodscurved(S shape),highlymo otile Microaerophilic (requirespecialmedia m andgrowth conditions42C, ,low O2). Catalase+,Oxidase+ CampyBacis selectiveforthis! ! G+anaerobicspo ore formingrod. Dx:demonstrate toxininptfecal specimen G+rod,nonmoti ile Anaerobic Doublezone hemolysisonbloo od agar. H2,CO2gas+

Invasiveaffectsjejunumtoanus(DISTALCOLON ).Mostcommonbacterialcauseofdiarrheaindeve eloped countries.Cryptitis,absc cesses,,ulceration(needto odifferentiatefromIBD).Lowerabdominalpaintod diarrhea inhours(wateryordyse entericw/blood/pus)+feve er.Resolvesspontaneouslyindaystoweeks,cangiv ve macrolides,fluoroquinolonesifsevere. Diarrhea(canhap ppenevenifnoninvasivest train) Dysentery Entericfeverifpro oliferateslaminapropriaa andmesentericlymphnode es ComplicationsGuillian nBarre,reactivearthritis Stool:PMN,RBCs Antibioticassociateddia arrhea(Dysentery510day ysafterantibioticcourse wateryorbloodyw/abd dominalcramps,leukocyto osis,fever)whichcanfurthe er developintopseudomem mbranouscolitis(colonis coatedw/plaquesoffibrin n, deadepithelialcells,mu ucus,andinflammatorycellls).Seeneutrophilserupting fromcrypts. Dx:findcytotoxininsto ool,cangrowonselectivem media Tx:discontinueantibioti icimplicatedinproblem,tr reatAADw/vancomycinor metronidazole,relapses scommonduetopersisten nceofresistantspores.

Clostridiumdifficile

Enterotoxin(GIupset)andcytotoxin(killsmucosal m cells)leadto thelialcytoskeleton,lossof o tightjunctions, disruptionofepit cytokinerelease,andinflammation. stightjunctions ToxinA:causescellroundingandinterrupts ty/secretion alterspermeabilit ToxinB:cytotoxic c(altersnormalintestinalflora) f Binarytoxingene esmarkersofhypervirule ence.

Normalflorain~5 5%ofhealthypeople.Canget nosocomially(but tcommunityacquiredisbe ecomingmore commonfluoroq quinoloneresistantstrainw/ w toxin production).Riskfactorsadvancedage,ho ospitalization, estinalflora antibiotictx.Antibioticsdisruptnormalinte andeitherpermitovergrowthbyresistantorganismsor makepatientmor resusceptibletoacquisitionfrom environment.

Clostridiumperfringen ns

Sporeforming, Noinvasion EnterotoxinintracellularCa,altersmemb branepermeability.Lossof o cellularfluid, macromolecules Mucinase:burrow wsintomucouslayerofsto omach,residesthereattac chedtogutepithelium. Adhesins(BabA)adheretosurfaceoffove eolarmucuscells.Notinfo ociofintestinalmetaplasia a. Enhancesbinding gtorbcsw/Bag. Urease:makesam mmonia+CO2fromurea(buffers ( gasricacidnearby) ) Expresstoxins(Ca agAregulatesVacAcause escellinjury,damagesgas strictissue,permeability yof epitheliumtoure ea) Causeelaborationofphospholipasesthatdamage d surfaceepithelialcells c (proteases, b downgastricmucus) phospholipasesbreak Doesntinvadetissues,butinducesaninten nseinflammatoryandimm muneresponse(IL1/6/8, TNF) adtogranulomas. ImmunogeniccanattractB/Tcellsandlea Plateletactivating gfactorcancauseocclusio onofsurfacecapillaries Hpyloritakesadv vantageofmucuslayertha atcoversstomachliningfightacidviaureaseenzym me convertsabundan ntureatobicarb+ammon nia.Itlivesinmucusliningofstomachwherebodys naturaldefensesdontreachuntileventuallytheycauseanulcer. LLOhemolysin AcAprotein enicstrains4bmostcommon(causesfoodborneli isterosis) 3humanpathoge Spreadissimilarto t groupBstrep Horizontaltransfe erfromcelltocellmeansthey t arentexposedtoimm munesystem Cancauseplacen ntatoinfectfetus,caninfec ctfetusinvaginalcanal

Waterydiarrhea N/D/painw/outvomiting gorfever Somestrainscaus senecrotizingenterocolitis spigbowelofcolon/ile eum Gasgangrene Tx:Prostacycline, clindamycin,broadspectr rum Mosthaveasxgas stritisbutareatriskofd developingPUD(1020%develop) andgastricCa Gastritis:an ntrum(mostcommonhig ghacid,highriskofduoden nalulcer), pangastritis s(leadstomultifocalatrop phy).Earlyseeerythemato ous mucosa.La ater,coarse/thickenedruga alfolds,evennodular.Latest atrophy.M Microscopic(biopsy)seeo organismsONfoveolarsurf faceand neckcellMU UCUS.Canbeseenw/H/E E,Giemsa,silverstains.Ne eutrophils (epithelial)a andplasmacells(laminap propria).lymphocytesand aggregregat tesw/germinalcenters(inducedMALT).Noninvasiv vetest detection= ammoniuminbreath,bac cteriainfeces,absinserum m Weirdfact: peoplew/duodenalulceronlyhaveHpyloriintheir r stomachs perhapslinkedtoacidproduction? *1causeof f duodenalulcers #2causeof f pepticulcers(behindNSA AIDs) Majorcauseofstiillbirth,spontaneousabort tions. algia Primaryinfection sxin1wkN/D/pain/mya monthslaterconstitutiona alsx,meningitis. Disseminatedm nmononuclearphagocyte esandepithelial,otherno on Intracellularwithin professionalcells s.Entersviainternaline escapesphagosomeviaLLO hemolysinrepl icatesincytoplasmuse esAcAtohaveactintoprop pellikea mbranes. cometw/theirtaillhorizontallythroughmem

usinsoil R:Ubiquitou T:Oralfecal

Helicobacterpylori

Gnegcurvedrod. Flagellaallowmo otility inmucus.

Notsureoftransmission t mtoacquirein routeseem ndhaveit childhoodan ecades. persistforde

Listeriamonocytogene es G+rod Catalase+ Betahemolytic Dx:Gramstain

food Birds,fish,mammals, m them a Wedefendagainst w/CMIhighriskif mp,young,old immunocom ntfor Tx:Amp/Gen fulminant,alsosensitiveto e,TMX/SMX prostacycline

BugsList,continued
Vibriocholera GRod,highlymo otile Fermentsglucose ebut NOTlactose Flatyellowcolonies onTCBSagar Oxidase+ TCP(toxincoreg gulatedpili)adhesion: Bundleformingpili,requiredforadh herencetointestinalepithe elium Encodedonpathogenicityislandonafilamentousbacteriopha age. ReceptorforCtxphage(encodescho oleratoxin)#percellcan namplifyinvivo ABsubunitprote einexotoxin:typeIIsecretion(holotoxinisformedin nperiplasm) B(binding) )bindsGMgangliosideatbrushborderofSIepithe elialcells,facilitatesAentry. A(active)isADPribosyltranferase: ADPribosylates/inactivatesguaninentprotein (regulatesconversionofadenylatecy yclasefromactiveinactiveform)locksproteinin nto activeGTPboundstate.Resultisper rsistentadenylatecyclaseactivation,elevatedcAMP. OpensCFTRchannel(hypersecretewater/Cl, w blockNa+absorpt tion)leadstowatery N pertussis,diphtheria ahavesamekindoftoxin! diarrhea.Note Toxinproducedat a mucosalsurface,bindsGM, G istransportedintointe estinalepithelialcells Choleraseverew watery(ricewatermucu usflecks)diarrheaduetoin ngestion ofORGANISMnot tatoxin.Littledamagetointestinalmucosaalleffe ectsdue totoxinandresult tingfluidloss/electrolyteimbalance. DOESNOTINVAD DE.NOhistologicchange. Mortalityduetod dehydration(>60%ifuntx).Overallgutaborptionisin ntact Tx:fluids/electroly ytes Prevention:impro ovesanitation.Vaccinesex xistbutdontprovidelongterm immunity Oralfecalsp pread ontaminated Reservoir:co water/food.Needto 8cfu. ingest~10^8

Vibrioparahaemolytic cus

Yersiniaenterocolitica a

Gcommashaped rods Motile Halophilic(saltlo oving) Gramnegcoccob bacilli Oxidase,Catalas se+, glucosefermenting RequiresFefor growth,difficultto t isolate Bipolarstaining G+sporulatingro od Motile

molyticcytotoxin Enterotoxin,hem

Baciluscereus

Yops(yersiniaoutermembraneprotein)dis sruptscellularfx, cytotoxic. Virulencefactorexpression e regulatedbyCa a++,temp. Canparalyzephagocyticabilityofcell Penetratesilealmucosa, m multipliesinPeyer rpatches/regional lymphnodes.Bacteremiarare,usuallyseen nw/Feoverload Heatstableemet tictoxinthattriggerssever revomitinganddiarrhea Enterotoxins

ParacholeraW Waterydiarrhea.Relatively ymildcomparedtocholera a. Bowelinflammatio on. Onset24hrs,lasts s3days Usuallyselfresolv vingcanusetetracycline, ,ciprofloxacin Cancausedysenterylikediarrhea. d AffectsRLQarea a(ileum,appendix,rightco olon).EnterthroughMcells msoflaminapropriaandPeyerpatches,draint tomesentericlymphnode es. Bowelthickwall,mucos salbleeding,ulcersenlarg gedPeyerpatches.MESEN NTERICLYMPHADENITISW /NECROTIZINGGRANULOMAS.Mimicsacuteappen ndicitis,Crohns. Canhavepolyarthriticsyn ndrome1monthafteriniti alinfection(resolves36m months).Erythema nodosum(nodulesonlegs s,resolvesin1month) Tx:notusuallyrequired.Severe S usedoxyclyclinea andaminogly;coside,bactrim,orfluoroquinolone Foodpoisoning:V VOMITING,diarrhea Onsetin16hours s,Usually<24hrduration Foodpoisoning:V Vomiting,diarrhea(cantrig ggerotherthingsliketoxic shockifgetintob lood) s, Onsetin24hours hrduration Usuallyafter<24h Fordxwanttoc culturetheingestedFOODnotthestool! Nausea,vomiting,,dizziness,cranial palsy,doublevisio on(mydriasis). Oftenininfants NOcarrierstate nevergoeschronic,but23relapsescanoccur. 3wkincubation,a acuteonset.LOWFATALIT TY Sx:fever,jaundice e,nausea,anorexia.1%go otofulminanthepatits. Tx:supportivecar re Px:passive/active e immunization Canhaveacarrier rstate.Chronicin10%ofi immunocompetentpts Serumsicknesspr rodrome(510%)vasculit tis(PAN),polyarthritis, membranousGN. 426wkincubatio on incidenceofhe epatocellularcarcinoma Sx:fever,jaundice e,serumsickness,arthritis, ,anorexia,nausea,RUQ pain.Hepatocyte damagesecondarytoTcellresponse.Hepatocytes havegroundglas ssappearance Incubationtakes4 26wks. Canhaveacarrier rstate(chronicin70%) Sx:mildhepatitis( (jaundiceNOTcommon). Assocw/posttrans sfusionhepatitis,typeIMP PGN,alcoholexcess,PCT, riskofhepatocellu ularcarcinoma.Intermitte entlyhighALT Dx:AntiHBCabs, RNAtesttoconfirm Tx:IFNa,ribivirin,,livertransplant

Shellfish,raw wfish(25%of foodpoisoni inginJapan)

Canspreadsystemic cally. riskinhemochrom matosispts. R:Worldwidecont taminated food, T:fecaloral.Highestratesin European/Scandinav viancountries (lowestinUS/UK) Associatedw/riceth hatiscooked andthenkeptwarmspores germinateintherice eand vegetativecellsprod ducethetoxin R:humanskincont taminated foodpreparercanca auseit. fficiently Infoodsnotkeptsuf warmorcoldespeciallyeggs, custard,mayo Endosporesinsoil y Cannedfoods,honey T:Fecaloral enters,prisons, Occursindaycarece travelerstodevelopingcountries, anal malehomosexuals(a intercourse) Shellfish

Staphylococcusaureus Clostridiumbotulinum m G+rod,sporefor rming Anaerobic HepatitisA Picornavirus,Nak ked, +ssRNA StableatlowpH, inactivatedbybo oiling

SomestrainsproduceheatstableSuperAgenterotoxins Superagto oxinsextracellular,overst timulateimmunesystemby ybindingMHCII/CD4and forceassoc ciation.Dontneedtobeprocessed p byagpresenting gcells,actaspolyclonalTcell c stimulators s

PotentneurotoxininhibitsAchreleaseatmyoneural m junctioncausesflaccidmmparalysis romingestionofpreforme edtoxin Foodpoisoningfr

AntiHAVIgM=ac ctiveinfection. AntiHAVIgG=re ecoveryfrominfectionorvaccination(protective) ericmucosaliverviremi ia/infiltrationoflymphoidcellsnecrosis/proliferat tion Replicatesinente ofKupffercells.Amount A ofnecrosiscorrela atesw/diseaseseverity.

HepatitisB

Hepadnavirus, enveloped,circular dsDNAw/gaps (smallestDNAvir rus) Coreprotein w/HBcAg

Daneparticles Cansurvive extreme conditions outsidethe body

T:parenteral,sexual,vertical skof (pregnancy90%ris transmissionduringdelivery, od breastfeeding),bloo transfusions.Presentinallbody fluidsEXCEPTstool. Thereisavaccine

HepatitisC Flavivirus,envelo oped, +strandssRNA E2,NS5AhaveIFN Nactivity

T:parenteral,sexual,blood transfusion elopeprotein NovaccineE2enve thighly isvaccinetarget(but ccine variablemakesvac developmentdifficult)

BugsList,continued
Hepatitis D Circular,ssRNA, surroundedbyde elta ag. UsesHBsAgasco oatproteintoinfect Disadudbyitse elf,butwithBitsprettyba ad Canhaveacarrier rstate.Chronicstatelessl likelyw/coinfectionthan superinfection RequiresHBsAgto oreplicate(sohastohappenw/orafteranHBVinfec ction) T:parenteral,sexual

Hepatitis E

+strandRNA,nak ked

Rotavirus

dsRNA Detectvia immunoassayNO OT culture

Calicivirus (Norwalk virus, noroviruses) Mumps

ssRNA

o chronicstate. Nocarrierstateor 40dayincubation n.Infectionoftensubclinic cal.Ifsxonlycausesacut tedisease,Fulminanthepa atitismaydevelopinpregn nantwomen(20%mortalit tyinpregnantwomen) T:Fecaloral (waterborne) reresolution. Sx:24wksbefor Happensindeveloping d xALT/AST,Sx,IgMIg gG countries HEVRNA,virionsinstoolandliverbeforesx DxviaIgMabs. Causesvomiting,wate erydiarrhea,fever,dehydra ationinchildren.Nofecal lwbcsor Virusisingested,capsuleaidsinsurvivalofstomachacid. Oneofmo ostcommoncausesofserio ousdiarrhea rbcs.Prodrome28da ays,mostlyaffectsduoden num,jejunum(stomach,LB B,SB) inchildren n.Ubiquitousworldwide,occurs o year Asxinadults. Multipliesinmatureepithelialcellsattipsof o villiinsmallintestine round.95 5%ofchildrenaffectedbyage a 5,most causeslysisof cellsleavingimmaturecel llsthatdontabsorbas age624m mo *1causeseverediarrh hea(death)inchildrenno owvaccine. wellloseelect trolytes,reducedreabsorptionofwater T:Oralfec callotsofvirusshedinfe eces. diarrhea/dehydra ation. ROTAZYMEtestinfecesestablishesdx Dx:immunoassayofst toolforvirus Gastroent Diarrheaw/N/V(outbreaks ( ofgastroenterit tisfromcommonsource)MOSTCOMMONCAUSEOF O ADULTGASTROENTERIT TIS teritisoutbreaksfrominfec ctedfood 2448hrincubation,1260hrduration.Selflimiting,Effectsinsmallintestine i (seelymphocytes sinLP+SE,SEvacuoles,br rushborderloss,spruelike evillus handler #1causeo blunting) ofoutbreaksofsecretorydiarrhea d Stool:Norbcsorwbcs worldwide e,alsocommonlycausesporadic Histo:Lymphocyt tesinLP+SE,SEvacuoles, ,bruishborderloss,spruelikevillusblunting infections.Stomach,smallbowel. Inhaledlungs replicatesinTlymphocy ytessalivaryductcells Ms,lymphocytes s,plasmacellsaccumulate e prodromeparotidglandinflammation.Parotitis, Sxflulike.3wkp gitis,pancreatitis,ovary,orchitis. constitutionalsx. Alsoassociatedw/mening Waterydiarrhea,flatulence,steatorrhea Canblockabsorptioninsmallintestine(duodenu umhasbluntedvilli, lymphocytes/plasmacells c andhastheseorganism msadheredtotheepitheli ium) Stool:foulsmellingste eatorrheaw/N/V/abdpain n,flatulence.Monocytes,c cysts. Lactasedefin2040% Tx:metronidazole,trea atwaterw/tinctureofiodiine. Liquefactiveflaskulcers:Trophozoitesburrow formflaskulcersincecum m+LB.Can havelungmigrationph hase(40%gotoliver,rarellymigratetolung) Grossly:seeulcers(normaltissuebetweenulcers rsgreatestamountinthe ececum. Complications:strictur res(ifcircumferential),live erabscess(solitaryormult tiple,looks likeanchovypaste inflammation/shaggyfibriinlining+centralhemorrh hage,can causelungabscess) mmonly Inhaled,com pediatric MMRvaccine

ssRNA Paramyxovirusfa amily Giardialamblia Flagellatedprotozoan thatparasitizesGI G tractofhuman,other o animals Trichromestain

Hemagglutin,neu uraminidase,hemolysin

Cysts=infectivestage s (persistinenvironme entalwater,onfood, fomites) phozoitesonceingested,ca andivideandmultiply Developintotrop Developbackinto ocystsincolon Doesntinvademakeaproteinlikeatoxin n(giardin)thatcauses waterydiarrhea.Bothformsinfeces. Colonizecolonicepithelium. e Ingestcystsinfoo od/water.Excystationinsm mallintestine, trophozoitesmigratetolargeintestine a infectlungs,liver Invadeintestinalmucosa,cangosystemicand n (rightlobe),brain Spreadwhenqua adranucleatecystissecret tedinfeces Movesviapseudo opodia.Cystsresistanttogastricacid LectinbindsCHOonrbcs,attachestoepit thelium. Amebaphorech hannelformingprotein hostcelllysis

treams, Primarilyw waterborne(mountainst beaverdams) houtIgAorlowIl6.havesevere Thosewith infections Smallinfectiousdose(cystresistanttostomach acids) ystsinstool Dximmu unofluorescentstainforcy

Entamoebahistolytica a

Oralfecaltransmissionofcysts. exuals, WorldwideRiskinmalehomose tionalized travelers,recentimmigrants,institut

Tx:metronidazole,trytopreventbyboilingwate er,goodsanitation Bloodinstoolindicatesactivedisease. Spts(300% Expecttoseeinchildren<5yrs,AIDS nUS)highlyinfectious immunein e. Foundinw water,food,soilworldwide nofluorescentstaindetectsoocystsin Dx:immun stool

Cryptosporidium parvum

Oocystsingested Sporozoitesareactive a form Obligateintracellular parasite(lifecycle ein infectedenterocy yte.

Survivesharshco onditions(bleach),freezing gkills. Ingestedoocystsareactivatedbygastricac cid. cspherules)adhereto Sporozoitesarereleased(25umbasophilic e,mostlyterminalileum,Rcolonengulfedin epithelialsurface vacuolesinmicro ovili.Nomucosalchangesunlessmassive,persistent infectionvilousblunting,atrophy,inflamm mation.

Cryptosporidiosis:Wat terynonbloodydiarrhea.V Villousatrophy,cryptenla argementin jejunum Malabsorptionmayoc ccurifpersistent.Biliarytr ractinvolvementinAIDS

Importantme edia/teststocons siderwhendxinf fectiousGIdisease:

MacConkey:Selective(onlyallowsGtogr row),Differential(LactosefermentermakesredcoloniesexEcoli,otherGlactosefermenters) HektoenEnteric c:Differential(onlyGandnonfastidiousgrow),Diffe erential(lactose/sucrosefe ermentersmakebrightora angecolonies,nonlactose/ /sucrosefermentersaregr reen/bluegreen,H2Sprod ducersmakeblackprecipitate) CNA(ColistinNa alidixicacid):SelectiveMed dia(G+onlygrowonit) Campybloodag gar(CampyBAP):Selective eisolatescampylobacterfrom f fecalspecimens TSI(TripleSugar r): o Butt(lacto ose)/Slant(glucose) o Kalkaline e(nonfermenter),Aacid(f fermenter),GGas. o Ex:Ecoli=A/AG.Salmonellatyphi= =K/A+G.Shigella=K/A.Ps seudomonas=K/K. MotilityAgar:St tabsemisolidagarincub bate24hrs.Ifmotile,orgwill w diffuseintomediuman ndcauseturbidity.Ifmotileseeconeofturbidity.Nonmotileorgonlygrow alongstabline. Oxidasetest:Ec coliisoxidasenegnocolo orchange.+testhascolon niesturnpurpleblack. Indoletest:Dete ectsifbacteriacausesredu uctivedeaminationoftrypt tophan,producinganindo ole.+testhascolorchange etopinkin30seconds.test t hasnocolorchange. Ecoliispositiveforthistest,klebsiellaisnegative.

Osmoticdiarrhea: Definition:in ntraluminalosmolalitylitt tle/nopassiveelectrolyteabsorption a ingut,cannotsustain s osmotic gradient.3.mL Lwaterretainedinlumenfor f eachadditionalmOsm.stool(water)osmoticgap. g 290292 0mOsm/kg.Unabsorbedosmols o watervolume eoverwhelmsthecolon (Na+K)=gap>50 Causes:Laxative es(Mg,SO4,PO4,PEG),No onabsorbablesweeteners(mannitol,sorbitol),CHOmaldigestion (intraluminald disaccharidasedeficiency,pancreaticexocrinedeficie ency),Malabsorption(mur ral)tolesser extentCeliacs sprue,othersmallboweldiseases, d Fasting/stoppingoffending o agent/stopsdiarrhea d Secretorydiarrhea: Definition:Nets secretionofwater(morecommon c thanosmoticdiar rrhea).Disruptedmucosalabsorptionand secretionsec condarytodisorderedelectrolytetransport.DrivingforcesusuallyCl/bicarbsecretion, inhibitedNaabs sorption.Stoolwaterosmoticgapnot.290292(Na+K)=gap<30mOsm/kg g.Unaffectedby fasting. Bileacidsifmalabsorbed,reachcolon,stimulateH2Osecretionvia acAMPsecretion.Excee edscolon acitydiarrhea. absorptivecapa Steatorrhea:OH HFFAhavelaxativeeffecton o colon.Malabsorption(T TGsdigestedtoFA,inhibitingcolonicwater absorptionse ecretorydiarrhea).Maldig gestion(luminaldefect)likepancreaticinsufficiency yTGsnot digested,theore eticallylessdiarrheaalthou ughstoolbulky/soft. Alsocausedbyn noninvasiveentericinfect tions(bacterialcoleratox xin,Cdifftoxin,ETEC,Cjejuni,rotovirus, norovirus,aden novirus)

Motilityabnormalities Luminalflowdependsonpressuregradients. Directionandspeeddue etostrengthandfrequenc cyof contractionsnupstream,resistancedownstream. flowtransittime(exIBS,diabetic ma,bacterialovergrowth,b bile neuropathy,scleroderm aciddeconjugation,thyr rotoxicosis) Smallbowel/rtcolonsee s veryhighvolume,wate ery stoolsfromsecretion/absorptionoverwhelm ming attygreasy,malodorous colonorlargevolume,fa Largebowel(especiallydistal) d smallvolume,mu ucusy bloodystoolurgency,tenesmusfrom distensibilityofinflamed dstiffwall Acut te s(travel,camping, Includesmostinfections hospitalization,epidemic),assocw/meds(antibiot tics, H PPI,chemotx);Dieta antiHTNsBblockers,H2RBs, ary (dairyproducts,nonsug garsweeteners,rarefood allergy,stres

Watery/blo oodystool rhea(ifnot Generallylittleworkuprequiredunle essseverelyill,bloodydiarr infection,c considerIBD,bowelischem miainelderly),epidemicsettinghospital setting,ant tibioticusehx,seriouscom morbiddisease. Chronic Maypresen ntasrecurrentacute. Includesfunctional(IBS),meds(surre eptitiouslaxativeuse), malabsorpt tion/maldigestion(celiacsprue,disaccharidasedeficiencies, temicdisease chronicpan ncreatitis,IBD),previousG GI/biliarytractsurgery,syst (HIV,DM,t thyrotoxicosis,malignancie es) LargerDdxthanacutediarrheafocu usonprobabilities o IBS:If<50,noredflags,fitROM ME3criteria o IBDendoscopy,biopsies o Disac ccharidasedeficiency:dod dietaryexclusion,H2breathtestafter inges stingsuspectedsugar o Mala absorptiontestHb,PT,Ca a,stoolfat o Celia acsprue:testIgA,transglu utaminase,endomysialab,smallbowel biopsy o Surre eptitiouslaxativeabuse:te eststoolforlaxatives o Infec ctions:Lookforgiardia,C.j jejuni,HIV,etc

Radiology
Contrastagents: SupinevsUprightabdominalXray: NormalMucosal AcuteAbdominalSe eries Radioopaquematerial Supine:airinbod dyofstomach,transversecolon c (anteriorstructures) folds: Supineabdom men(KUB/flatplate) administe eredtosee Prone:airinfund disofstomach,rectum,asc cending/descendingcolon Valvulae Uprightabdo omen:detectsairfluidleve elsandfreeintraperitonealairhorizontalbeamparalleltoflooris structures s/pathologicprocesses Upright:airinfun ndus conniventesof o used.Ptneed dstobeinuprightposition natleast10minpriortora adiograph thatwouldnotbeseenotherwise Decubitus:Rtside eairinrtcolon/duodenu um;Leftsideairinleft smallintestin ne Chestxray:d detectsfreeintraperitonea alair/chestpathology Usefulones:bariumsulfateinGI colon/stomach Haustraof LLDecubitousabdo omensubstitutesuprightviewindebilitatedptpt tneedstomaintainposition10min tract,Iodinecompoundsin ReadingtheXRay:ABC CDApproach: colon vessels,CO2invessels/GItract, Air(pattern,freeair) GastricRugae e naturallyoccurringairinGItract Bone(anychange eshappeningaffectingptsx?) s ofstomach Intestinalmotilit ty Calcification(uret teral,gallbladder20%calcified,pancreatic?) Evaluated dbyfluoroscopy: Density(anyabno ormaldensity,softtissuemasses? m Dosize/configof intestinalobstruction,paralytic normalorganslookok? ileus(lack kofperistalticactivity), Smallbowelcanbeex xtensionofupperGIexamfollowbariumthrough intussusce eptions, bowelw/serialfilms.En nteroclysiscanalsobedon ne(canidentifybetter Pneumop peritoneum mucosaldetail). MechanicalObstructionofSmallbowel MechanicalOb bstructionofLargeBowel Paralytic P (adynamicileus):The T bowel Penumoper ritoneum:Freegasinperit tonealcavity Contraststudies: Smallbow weldilated>3cmw/gas Distende edcolonfromcolontoleve elofobstruction lu umenispatent,butfunctio onal Com monlyduetoperforationofGItract(pepticulcer), Bariumorwater (swallowe edair)andfluid(excretedby b w/airan ndfluidinside defect. d propulsiongen neralizedor Follo owingsurgicalprocedure(laparotomy) solubleagentsusedto digestiveglands).Formsmultipleai irfluid Incompe etentileocecalvalveletsga asbackwardinto lo ocalized Xray ysigns:onerectabdomina al/chestfilmacurvilinear r(small fillthelum men levels.Pla ainabdominalfilms(erectand smallbo owel Largeandsmallbow weldilation, amou unt)orcrescent(moderate eamount)oflowdensityg gas indirectly yhelpevaluate supinevie ew)toconfirmthedx Dilatedcolon c indistaldescendingandsigmoid occasionallystomach hdilated area betweenopacityofdome eofdiaphragmandliveron nthe themuco osa. Multiplea airfluidlevels,stepladdering Commonlyduetocancer,volvulus s(midgutinchildren, also right t mostreliablesignforidentifyingthiscondition.W Withno Evaluateforbarium (intestinalcontentsmovetowardre ectum, cecalinadults,sigmoidinelderly) Commonlydueto furth hergasorotherconditio onthefreeairwillbeabsorbed extending goutoflumen fluidpush hedupoverloopsdifferent Uprightviewshowsmultipleairflu uidlevels(largerthan intraabdominalinflam mmation, in71 10daysormuchfaster(12days)inchildren (ulceratin ng, levelsind differentareas) thosese eeninsmallbowelobstruct tion) postsurgicalorposttr raumatic Exs seeCurvilinearareabetwe eenrtdiaphragmandliver r inflamma atoryprocess) reaction,spineinjury y UpperGIExamination Bariumenema:Bariumcoats mucosa,followe edbyCO2. Coatingofmuco osaand distendedw/gas.Appendixis filledw/barium also

Esophageal carcinoma

Malabsorption:willsee changeinappeara anceof bariumcolumn segmentation,flocculation, dilution,separatio onof loops.Sprueexin npicture

Achalasia: Dis stended eso ophagusw/distal bi irdsbeaksign oft tenseefoul odors,vomitingof eso ophageal con ntents

Boerhaav es syndr rome (transmur al perfo oratio nse een w/vo omitin g, bulim mia),

MalloryWeiss(n nontransmural tearcausedbyse evere retching/vomitin ng)Othercauses ofesophagealru uptures:, iatrogenictraum ma(8590%of cases),foreignbo odytrauma

Gastriculcersbenignulcer(u ulcer proje ectsbeyondgastriclumen, , sharp pmargin,roundbariumdo ot view wedenface,edematoushalo aroundulcerinacutestage,ga astric folds sradiateoutlikespokesof f whee elinsubacuteorchronicst tage, perfo orationleadstolargeamounts offre eeintraperitonealair).

Neoplasmsinstomachwall ormasslooks silhouettetumo ctextending likeafillingdefec mn.Irregular intobariumcolum fillinginstomach isspace monlysee occupyingcomm as, GISTs(leiomyoma ,lymphoma) adenocarcinoma,

Linitis plastica:diffusenarrowingin proximalstomac ch,diffuse infiltrationoflym mphomainwallof stomach.Nomo otionon fluoroscopy(per ristalsisimpeded)

Duo odenalulcerstypically loca atedinbulb.Maybeassoc c w/g gastriculcers.Mayperfora ate, mos stcommoncauseofnon idio opathicpneumoperitoneum m. May ypancreatitis

Crohnsdise ease unknownetiology, transmural,can affectanypa artof alimentarytract, mostlyaffec cts terminalileu um, proximalcolon,may affectduode enum. Cobblestone e appearance(edema w/crisscrossed ulcers).Skip pareasof normalbowel.

Complication ns obstruction,fistulas, f abscess.Areasof narrowingse eparatedby areasofmorenormal bowel.Separationof loops,fistulas Diverticula a mucosapr rotrudes outofbow wel lumenthro ougha weakpoint ntinmm layer.

Diverticulosis multiple diverticula

Diverticulitis:com mplicationof diverticulosis,infla ammatory process.Causesp perforationof diverticulum.Infla ammatory processusuallyloc calizedand formspericolicabscess.Can developfistulasto ovagina, bladder,etc.Extra avasation fromlumenseen,abscess cavityw/bariumseenin picture.CanalsouseCT evaluation(seeinf flammatory processinthemes sentery w/aircollections)

 UlcerativeColitis: Unknownetiologymucosalinflam mmationandulcerationinla arge bowel.Al lwaysinvolvestherectum. .Earlywidespread fuzzy/serr ratedulceration.Laterigid dtubeappearance(Lead pipe)chronicscarringcausesnarrowing,lackofperistaltic activity,lo ossofhaustra,narrowing,smoothsurfaceofdistal colon/rectum.Complicationstoxicmegacolon,carcinoma.Late stagecanshowmarkednarrowing,abnormalsmoothnessw/loss ofhaustra ations. Coloncarcinoma a:abrupt narrowingoflum menascending colon,primaryn neoplasm lookslikeanAp pplecore

Appendicitis: A CTisusefulst tudy Irregulargraydensity y representsinflammatory changeinRLQinarea aof theappendix.Maysee stoneinappendix (fecolith).

TumorsofGItrac ct: Generalsignfilllingdefectmassreplacesbarium. Commonsignsof fUpperGItumorbybarium mmeal mass,constrictio on,ulcerationwhenmassg grows beyondbloodsu pply. Commonsignsof fLowerGItumorbybarium menema polypoidmassle esion,annularconstriction Cholecystitis:Us seUSEchogenicfoci (gallstones),thick kenedgallbladder wall,pericholecy ysticfluidmaybe difficulttodiscrim minateacuteand chronicdisease Dilatedcommon bileduct:causes includestone(m mostcommon), carcinoma.Doa longitudinalUS throughliverhilu umseetypical doublechannels signdilatedcommon bileductanterior rtoportalvein.Duct usuallysmallerth hanvein.USbest initialimagingmo odalitytoevaluatefor dilationofbiliary ytree.

Polyposis:canidentifyw/singlecont trastbarium enemas seemultiplesmallfillingde efectsfrom polyps(he ereditarypolyposissyndrom me).Polyps mostcommonlyfoundinrectosigmo oidalregion

Hepato obiliaryevaluation: Standard S radiographsmo ostvalueinevaluatingcalcifiedgallbladderstones(20 0%) Nuclear N med:lookateitherKupfercellsorhepatocyt tes,functionalevaluation US: U fast,inexpensive,fairly yaccurate,goodforGB,somefunctionalevaluationtheMOSTSENSITIVESTU UDY for f gallstoneandgallbladder.Appearround,echogenicseeacousticshadowi ing

Pancreasevaluation Imagingevaluationplainfilmsentinelloop p,calcifications (chronic);ultrasoun nd(enlargements,cysts),CT T(fluid collections,infiltrationoffat,density,lossof o tissue planes,calcification nschronic),MRI(fluidcollections, edema) Sentinelloop:dilate edduodenalcloopcau usedby irritationofretrope eritonealportionoftheduo odenum. Wideningofloopca ausedbyedemaorpseudo ocyst.

CTcolonography y: Minimallyinvasi ive examination,req quiressame prepascolonosc copy.Sensitive tosubcentimet terpolyps. Substituteforen ndoscopy.Still willrequireendo oscopyif abnormalityfou und. Completedevalu uationif normal.Radiationrisks.

CT: C moreexpensive,veryaccurate, a canevaluateforcontrast c enhancement,ion nizingradiation MRI: M mostexpensive,nora adiation,canusecontrastagents a specificallyforliver rreallygoodforhemangi ioma of o liver.Detectsironaccum mulationsinliver(hemochromatosis)futurevalueby b usingironcontrastag gents HIDA H imaging:radionuclide etargetedtohepatocytes. Nonfillingofthecommon nbileductorgallbladder indicatesobstructiveproce ess Sulphur S colloidscanlivermetastases: m labeltheRESsy ystem(usedlesstoday) Labeled L rbcstudylookfo orareasofuptake(seeinheart, h spleen,focalareainliverinthiscaseshowing ga hemangioma) h Plain P films:Gallstonescanbeseen(inthe20%thatactuallyhaveCa++)Appea arfaceted,denserimw/less dense d center.Separatedfr romrenalcalculiorcostoc chondralbydifferentpositi ions,morefilms.

AcutepancreatitisC CT:seeedema(densityin i fatty structures)andloss softissueplanesaroundth hepancreas. Fluidcollections(ps seudocysts).Diffuseinflam mmation Phlegmon(maydev veloptopseudocystsasenzymes breakdowntissuein ntheseareasofinflammation).