DIGESTTIVEDOMAIN

O
Esophagus
Normal: Musculariispropria:innercircularmm,outer
Embryology:Fromccranialforegut,existsbyw wk3 longitudin
nalmmw/myentericplexu us(Auerbach);
gestation Adventitiaa
Anatomy:goesfrom mC6T11/12.~25cminad dult.
3Narrowings:cricoiidcartilage,aorticarch,diaphragm
Wall:
Mucosa(smooth,gllistening,pinktan)nonkeeratinizing
stratifiedsquamoussepitheliallayer(maturesq quamous
dcellsoverbasalresservecells),laminapropriaa(areolar
CT,vascular,leukocyytes,haspapillaethatgointo
epitheliallayer),muuscularismucosa(mmw/lo ongitudinal
orientation);
Submucosa:looseCCTw/vessels/lymphatics,leeukocytes,
nerves(gangliaofMMeissnersplexus),glandstthatsecrete
mucin;
Esophagealphase:mmovementalongesophagu us(Problems25secondsaafterswallowing,usuallyasssociated
Oralpharyngealphase:transfe eroffoodfrommouthe esophagus(Problemsupon n LowerEsophagealrelaxation/entranceinto
w/spasm/carcinomaa)
swallowingusuallyfromneurromusculardisease) stomacch:(problemsassociatedw w/narrowingat
PrimaryPeristtalsis:initiatedbyswallow
wingUESopens,foodpusshedinbyperistalticwavethatstartedin
Bite/chew:Startsbefore eswallowingodor/taste//sightgenerateafferent lowereendofesophagus).LEShasno
pharynx(24ccm/sec),UESthencloses.LESopensandthenclosess.Contractionsdontgoto ogastric
impulsestomedullawhiichsendsimpulsestosalivaarygland,stomach, anatommicalmarkermadeofsmoothmm
musculature
pancreas highprressurezoneof24cmbetweenlower
o UES:atlevelofcricopharyngeusm mm.Highpressurezone,ccorrespondstolowerpharyyngealmm
o Salivate:flowisA
ANSregulated(Achparasym mpatheticinputstimulates esophaagusandstomachresulting gfrom
group.24cmlength.Resultsfro omtoniccontractions.Itreelaxesduringswallowingrreflex.Its
+smell,chew,tastte,nausea,conditioning,e esophagealdistention; continuuous/toniccontractionsof circular
purpose eistopreventairfromentteringtheesophagus.Dyssfx=zenkersdiverticuli,criccopharyngeal
Swallowing sleep,fatigue,deh
hydration,fear),canbeaffectedincompositionby smooth hmm.Preventsgastriccontentsfrom
achalasia.
ADHandaldostero one.flowratealsoN Na+/bicarb/Clcontent, movinggfromstomachesophagus.Relaxes
SecondaryPeristalsis:initiatedwithoutswallowingoranyCNSinpputpropulsivecontractionsare
K+content w/swallowtoallowfoodtoenterrthestomach.
stimulatedbyesophagealdistention.Im mportantformovingfoodaandrefluxedacidtostomaach.Enteric
o Salivaishypotonicc,hashighK+.Containsanntibacterialagents (tone
bygastrin,Ach,5H,PGF2 2a,motilin,
nervessenselloweresophagealdistensio onandsignalinterneuronss(atmyentericganglia)tosignalmotor
(lysozyme,lactofeerrinIgs,fluoride,Ca++,alp
phaamylase,lipase). SubP,Histamine,Pancreaticpoly ypeptide;tone
neuronstocauselocalcontraction.
CoordinateSwallowing:CNSvoluntarycontrolto onguecontractshard byNNO,VIP,Coee,fats,EtOH,
TertiaryPeristtalsis:abnormaloftenseeenw/age.Nonperistaltic,,spastic,uncoordinatedco ontractions
palate,movesbolusbacksoftpalateisforcedupnasalregurgprevente ed progesterone,chocolate,peppermint,gastric
occurindistallesophagus.
(epiglottisisup).Medulllacontrolsstriatedmmco ontrolofswallowing. pressure)
Refluxd dysplasia(intestinaltype)Barrettsadenocarccinoma
Traccheoesophagealfistula CongennitalDuplication
Atressia DiaphragmaticHernia(1:2000) Webs Rings Steno
osis
(1:3000) (Foregu
ut)Cysts
Thickkenedwallw/atrophiedmu uscularis
Goeestotrachea/bronchus Defectivediaph hragmclosure.Unilateral,most Upper,thin,sem
mi Lower,thick,,circumferential
Asxorccompressive. proprria.Mostareduetosevereinjury&
haaveothermidline Incommplete Lposterolateral.Portionofleafisabsent. circumferential. Mostlyin A(abovesqu uamocolumnar
Congenital Saclike,cysticmass,2 mmationresultinginsubmucosal
inflam
anomalies(espcardiac), devellopme Abdominalorgaansherniatedinto/fillthe 40+agedfemalee. junctionof
anomalies Canleadto
mmlaye ers.Adjacentto
nttthin thorax.Lungsaarecompressedduring PlummerVinsonn esophagus/sstomach)orB(at
scarriing.
orintramural.Ddx
aspiiration/pneumonia, cordor development lethalrespiratoryproblem msif syndromeIron GEjunction) Submucosalsoft
broncho ogeniccyst Canresultfromchronicreflux,iirradiation,
elecctrolyte/fluid blindpouch large(especiallyyleftsided).Lunghypoplaasia deficiency tissueledgesscoveredby
(cartilagge) caustticinjury,scleroderma.Canalsobe
imbalances (bilaterally).He
eartdisplacedright. anemia/glossitis//cheilosis mucosa
congeenital.
HiattalHernia:Diaphragmcrurrawidelyseparated;
DiverticulaOutpo
ouchesofGItract Lacerations(MalloryWeeiss)
wideenedspace.Mostlyinadu ults.
Sliding(Axial,95%);stomachslides Pulsiondiverticulum:
P MalloryWeisslongitudinnaltearsatGEjunction,cardiaHxofsevere/prolon nged
Epiphrenic Traction
T
abovethediaphragm.Bellshaped dysmotilityZenkers
d vomiting/retchingRiskkw/acutealcoholintoxicattion,Hiatalherniapredispo
oses.
diverticulum diverticulum:
d
dilattationabovediaphragm.SSx diverticulumjust
d Theorythatmmdoesnootrelax.Refluxinggastricccontentsoverwhelmthegaastricinlet
justaboveLES notamotility
n
reflu
ux,heartburn.Complicatio ons aboveUESDysphagia, contraction.Causesmasssivedilation,tearing(Injuryfrombelow)
nocturnal disordermidpoint,
d
ulceerate,bleed,perforate. egurg,neckmass.
re
fluidregurg nosx.Inflammation
n
Aspiration
A Grosslinearlacerationss,mmtocmlong;penetraatemucosa.Usuallysuperfficial.Microscopic
(TB,histoplasmosis)
( pneumonia
p traumatichemorrhageandacutetissueinflammaation.
Paraaesophageal(nonaxial):sttomach
Sx:UpperGIbleed,hemaatemesis
porttionbulges,wedgesintow
widened
Obstruction, Rx:generallydontrequiiresurgery,healingtendsttoberapid/complete.
spacce.Canstrangulate,obstru
uct.
MotorDysfx Ddx:Boerhaevessyndroome=distalesophagealtraansmuralrupturew/mediaastinitisafter
vomiting
Variices Achalasia
Torttuousdilatedsubmucosalvveins.Bulgeintodistaleso
ophageallumen.Collateralchannels FxobstructionofLES(doeesntrelax)hastone,aaperistalsis.Proxesophaguspainlesslydilates.Canb befromdamaged
betw
weensystemicandportalvveins. myentericplexus,lowVIP P
Prollonged,severeportalHTN(cirrhosisdevelopin90% %ofcirrhosispts,hepatic Causes:Primarilyunknow wn.Likelyrelatedtodysfxoofinhibitoryneuronsw/NO O,VIPindistalesophagus.Secondarycauses
schistosomiasisis2ndmostcom
mmoncauseworldwide). (rare)surgery,infiltrativvedisease,Chagas(T.cruziiidestroysmyentericpleexus)
Asxuntilrupture(massivehemmatemesis).Complications4050%mortalityin1st time. Sx:progressiveDysphagiaa,nocturnalregurg,wtlosss.Wallhypertrophiesthen nthinsasesophagusprogrressivelydilates.
%rebleedin1yr.Somemortalityperepisode.Ballo
50% oontamponadeorscleroth herapy Mucosaisnormalinflamed,ulcerated,fibroticassdiseaseprogresses.
usuaallyused(dontspontaneo
ouslysubside).Canseehep paticencephalopathy Complicationspulsiond diverticula(epiphrenic),squuamouscellcarcinoma(5% %),infection,aspiration,caandidaesophagitis
Candetectw/hepaticvenograam Rxlaparoscopicmyotom my+balloondilatation.Bootoxinjections.

EsophagusPatthology,continued
Reflluxgastritis(GERD):
refluxofgastricjuices/ccontentsinto
loweresophagus.Patho ogenesisfactors
thatexposuretogasttriccontents.
Contributingfactors antireflux
mechanisms.LESton ne,
Esophagitis intraabdomainalpressure.Eatingahigh
Inflammation
fatmealcancontributebycausingCCK
ofesophageal
release(whichgastricemptying,
mucosa
LEStone)
In5%ofadult
Sx:Dysphagia,heartburrn,regurgorsour
population,
fluid,hematemesis,melena(maybe
morein
mistakenforheartattacck)
northernIran,
Gross:hyperemia
partsofChina
Microscopic:epitheliialinflammatory
cellsespeciallyeosinoph hils,neutrophils;
elongationofpapillae(ttoupper1/3
epitheliumnormalisttolower);basal
cellhyperplasia(>20%o ofepithelium
normalis1015%)
Esop phagealcarcinomaaden nocarcinoma:
inciddence,especiallyin=
Riskk:w/documenteddysp plasia.Alsotobacco,obesity,radiationtx.
Grossearlyflatpatchesm massesinfiltrate,ulceratte.MostariseinBarrettsesophagusatGEjunction.
Microscopic=intestinaltype.Mucinproducing,glandfo
prod ductionidentifyamalignan ncyasanadenocarcinoma.welldifferentiatedhavemore,poorly
diffeerentiatedhaveless.
Pathhogenesis:Refluxbarre ettsdysplasia(criticalsttep)adenocarcinoma.SStepwiseaccumulationof
Neoplasms
geneeticandepigeneticchange es.Duetochronicdamage etocellsandDNA.Metapllasiacellproliferation,,
Dysp plasia%cyclingcellslossofcellcyclecontrol..
BarrettEsophagus
Infectious/Ch hemicalEsophagitis
intestinalmetaplaasiadistalpaletan
Irritantts:corrosivechemicals,pills,hotliquids,
squamousepithelliumisreplacedby
MMorphology:columnarintestinal heavyssmoking.
metaplastic(velvvetyred)intestinal
ttypeepithelium.Admixedgoblet Infectioous:candida,HSV,CMV(nuclear
epithelium.Aresponsetoprolonged
ccellsrequiredtomakedx.Caution inclusio
ons)
reflux.~10sxGERDptshavethis.
Riskfactorforadeenocarcinoma. endoscopicabnormalityaalso Iatrogeenic:cytotoxicchemotx,radiation,blood
nneededfordx.Complicatio ons vesselinjury
Sx:mostage406 60,GERDsxw/local
uulcer,stricture,adenocarci noma. Eosinophilic:numerouseosinoph hilsin
ulceration/bleedin ng/stricture
epithelliumespeciallynearthesurface.Sx
Dysplasiaprecedeesadenocarcinoma.
adultD
Dysphagia,foodimpaction.
Cytologicatypia(nnuclear
Infantss/childrenhavefeedingdifficulties,
characteristicslaargenuclei,
GERDllikesx.Noresposetolowdoseproton
cytoplasm,mitoses)+architectural
TLESSR(transientLESrelaxationn)occurs pumpiinhibitors,noacidrefluxon ntesting.Hx
atypia.Lowgradeechangeslesssevere
independentlyofswallowing,m maybeassociated ofatoppy(allergies,asthma,blooddeosinophilia).
thanhighgradech hangesinwhich
w/gaastricdistention,neutrallymediated.HaveLES Txavvoidfoodallergens,corticosteroids.Ddx
architecturalatyppiaisgreatest.
relaxxationfor530seconds.N ormalphysiological refluxx,
Architecturalchan ngesofdysplasia=
evenntswallowlotsofairbbelch,preventsgastric Intrammucosalcarcinomaglandssbreachthe
nuclearcrowding,,stratification,gland
bloating.Triggeredbygastricd
distention,pharyngeal basemeentmembranebutdonotinvadeinto
inglandformation,nobasement
mechanicalstimulationwhichcauseavagalreflux. submucosa
membranebreach h.
Squamouscellcaarcinoma:
Chronicessophagitiscausescellturnover.
Gross:70% %inupper2/330%inlowwer1/3.Squamousdysplaasia
Earlywhitteplaque,beginsasanintraepithelialneoplasia.Lattergeta
orming.Adjacentdysplasiaa.Glandformationandmucin
massthat invades,encircles,constriccts.Mayulcerateordiffussely
infiltratew
wall.
Microscoppicmostaremoderatelyttowelldifferentiated.Kerratin
productionn,lackofglands/mucinideentifyamalignancyasasqu uamous
cellcarcinooma.
Sx:ClassiccallyhasinsidiousgradualttumorgrowthlateDysph hagia
obstructioon.Dietchangeofsolidstooliquids.Extremewtloss.Usually
verylagettumorswhensx,oftenmettastatic.
Complicatiionsdebilitation,ulceration(hemorrhage/sepsis,fo
ood
aspiration ifcancertracheoesophageealfistulaforms.
MaleHotttea,carcinogens(othercoountries);smoking/alcohol(here)
Stomach
SecretionofAcid d:
Cephalicp phase:initiatedbytaste/sight/smell/chewing/swallowingoffood(vagalmediattion).Accountsfor3040% %ofacid
NormalStomach: secretion.StimuliactivateCNS,activatevagalefferentnnwhichstimulateneuronsinEN NStoreleaseAchorGRP(ggastrin
Allgastricsurfaccecoveredbyfoveolarglands.Deepglandstypevaries releasingppeptide).InhibitedbySNSS.Acidislowinitiallyfollow
wingamealbecausethisreesponsetakestime.
byregion;deepglandmucusmadeincard diaandpylorusisdifferentfrom Gastricphhase:stimulationofstretch hreceptorsgastrinreleassepromotedbyluminalaaas,vagalmediation.Accou untsfor
mucusmadeinffoveolarglandsthatprotectsmucosafromaciddigesstion. 50%ofacidsecretion.Gastricdisteentionactivatesmechanoreeceptorstoinitiatelocal/vvagovagalreflexes.Gcellssdirectly
Saccularvolum me=12001500mL,butcandistendto3000mL+. activatedbypeptidesaswell.Inhibiitedifgastricacidfallsbeloow3(somatostatinreleaseedunderacidconditions)
Mucouscells:in ncardia,antralregionseccretemucus,pepsinogenIII. Intestinalphase:foodenterssmalliintestine10%ofacidsecretion.Stimulatedbycircuulatingaasandaasinintesstinal
StimulatedbyAch,Prostaglandins lumen.Paathwaynotreallyknown.Inhibitedbyacid,fat,hypeertonicsolutions.
Parietalcells:in
nfundus,bodyveryeosin nophilic.HaveanH/KATPaase. Allsignalssleadto:Activationofprottonpump
SecreteIFtobinndVitB12forabsorptionin nileum,gastricacid. o Ach
hfromvagalafferentsstimulateM3cholinergicrecep ptors(activatesPIpathwayy,bringCa++intocell,activvateH2
Chiefcells:Secreteproenzymespepsinoge enI/II(activatedtopepsinin pummp)
pH<2).Verybassophilic. o Gasstrin(stimulatesCCKbwhicchactivatesPIpathwaytobringCa++intocell,activaatesH2pump)somatosta atin
Endocrine/enterroendocrinecellstriangu ularshape, inhiibitsgastrinrelease
o Gcellsinantrum(makegastrin); o Histtamineworkssynergisticallyw/Ach/GastrintoreleasseH2(stimulatesH2recept ptors,activatesadenylateccyclase,
o enterochrromaffinlikecells:makeh histamine,bindH2recepto orsto MPthisisthemostimportantfactor)PGE/IinhibiithistamineeffectsbyblocckingcAMPviaGiactiva
cAM ation
causeaacidproduction.
o Dcells:m
makesomatostatin(inhibitssGcellsecretionofgastrin and
parietalceellsecretionofacid).SecretionofinhibitedbyAch.
o Xcells:makeendothelin
MucosalProtectivemechanisms:
Epithelialcellsssecretebicarb(sopHisneu utralnexttoepithelium),q
quickly
replaceepitheliaalcellsviarestitution,high
hbloodflowremovesacidaand
restoresbicarb,
PGsfavormucus/bicarrbproduction;inhibitparie etalcellacidsecretion,impprove
mucosalbloodflow.

Ittakes9.1kcaltosecrete1molofHCl

Antralmucosa
Fundicmucosa

Peristalsis:initiaated/regulatedbyinterstitialceellsofCajalinmidportionofgrreatercurvatureofthestomach.Mm
Gastricmotility:
contractionsocccurwhenspikepotentialsappeearduringdepolarizingphaseo ofBER.Probabilityofcontractionbyvagal
Proximalstomach:storage/retentionoffood
stimulation.TheereisuniformBERfrequencyingastricmotorcells,butaphaaselagoccursfromdelayedsprreadingofslow
o Gastricrelaaxation:receptiverelaxation/accommodationoccursasmealenters.Vagalfibers(viaVIP,,NO),
waves
secretin,GIIPregulates.Thefundusrelaxe
eswithaswallow.Avagotomyywouldcauseaninhibitionofb beingable

torelaxyouurstomachupontakinginame eal!
Antralsystole:PPyloricsphincterpartiallycloseesduringperistalticwaveandrretropulsioncausesmixing/grin ndingoffood.
Distalstomach:grinding/mixingfoodhassloww waves(BER)andperistalsis
Liquidspassthrooughpyloricsphincterandenttertheintestine,butfoodcanttpassthrough.
o Gastricconntraction:pacemakercellsbetw ween2mmlayers.BERstartin ngreatercurvatureofstomach handoccur

throughouttGItractkeyinregulatingwhhenacontractioncanoccur.ABERisintrinsicrhythmicalflucttuationin
Pyloricsphincteer:regulatesentranceintointeestinefromstomachbyparticleesize.Gastriculcers,pyloricste enosiscanaffect
restingmem mbranepotentialofGIsmoothmmcells.SlowwavesstartininterstitialcellsofCajalandarrealways
this.
presentthheydictatewhencontractionscanoccurandarentalteredbyyhormones/nts.Instomach,B BER=3/min
o Excitatory:Ach(viaCa),SuubP(via Migratingmotoorcomplex:migratesfromstom machtoterminalileum.Occursevery90minutesintheinterdigestiveperiod.
(12/minindduodenum,9/mininileum,3/6 6incolon).Mmcontractionisinitiatedbyspikesrelatedto

Ca).Inhibitory:VIP(via cAMP), Sweepsoutthe GItract.Canhaveemptyingaftervagotomy,w/diabeticggastroparesis.Alsoinscleroderrma,muscular
intracellularCa++andoccuronlyduringthheplateauofslowwaves.Inteensity/frequency/durationofsp pikes
NO(viacAMP) dystrophy.eemptyingcanhappenw/gastrecctomy(dumpingsyndrome)VIPduetofoodinduodenum,
determinessamplitudeanddurationofmm mcontraction
enterogastricreeflex.
Chronic:Theprese enceofchronicmucosalinflam mmatorychangesleadingeventtuallytomucosalatrophyandiintestinalmetaplasia(usuallyw withouterosion).
Eoosinophilicgastritis:idiopathicceosinophils
Acute: Seelymphocytes,plasmacells(laminapropria),n neutrophils(epithelium).Intesstinalmetaplasia/atrophy(from mdamagerepair).
Gastritis in
nfiltratestomachwall(especiallyantrum,
pyylorus).Txsteroid.
Acutemuccosalinflammatoryprocess(traansient). Outcomenottransient.Mayprogresspepticculcercarcinoma,lymphoma.
Inflammatory Seeneutroophils(epithelium),congestion,, PathogenesisHpylori,NSAIDs.
Allergicgatroenteropathy:inkid dsdiarrhea,
edema,ero osion,hemorrhage. Individualsrespon nsedeterminesriskacid(aantralgastri s)pepticulceraation.acid(pangastri s) atrophymalignancy.
responseto voomiting,growthfailure,eosinophilsinbiopsy
Outcome transient(healsorfatal).Mayy H.pyloriGramnneg.Flagellahavemotilityinmucus.Adhesinsadhereto
mucosaldamage offantrum.
progressto oacuteulcers. surfaceoffoveolarmucuscells.Notinfociofinttestinalmetaplasia.Adaptedtto
bygastric Lyymphocyticgastritis:Tcells(CDD8)inbodyof Autoimmunegastritisschronicatrophicpangastritis(rare<10%chronicgastritiss).
Pathogene esismultiplesynergisticfactorrs. lethalgastricacidurease(ureaNH4+CO2 2),buffersnearbyacid.Express ss
sttomachcausesabdominalpain,anorexia, CD4mediateddestructionofparietalcells.D Diffusedamagetobody/fundussparietal
secretions Associateddw/heavyNSAIDuse,alcohol(ttendsto toxins(CagA).Anttrumiscommoninfectionsite,,besttobiopsyearlysee
naausea,vomiting.~60%assocw w/celiac (oxyntic)cellshypochlorhydria/achlorhydriaagastrinproducingcellsinantrum
following causehematemesis),smoking,severe erythematousmucosa.Later,coarse/thickenedrugalfolds,evennodular.Lateest
diisease. hypergastrinem miaECLcellhyperplasia riskofcarcinoidtumor.
disruptionof physiologiccstress. atrophy.Microsscopic(biopsy)seeorganismssONfoveolarsurfaceandneckk
GranulomatousGastritis:intram mucosal Intrinsicfacttor:B12deficiencyriskperniciousanemia.Absagainstp parietalcells,IF.
Sx:asxorvvariableepigastricpain,N/V.B
Bleeding, cellMUCUS.Canbeseenw/H/E,Giemsa,silverstains.Neutrophils(epithelial))
protective eppithelioidgranulomasfromCro ohns, Chronicpangastritis mucosalatrophyw/intestinalmetaplasia.Chronicpangasstritis00
hemeteme esis,melena(maybefatal).Risskof andplasmacells(laminapropria).lymphocytesandaggregregatesw/germi nal
mechanisms saarcoidosis,infection,systemicvvasculitis,or body/fundusareinvollvedparietalcellmass(atrop astri span
phy),acid.Hpyloriantralga
progressiontodeepulcers. centers(inducedM MALT).Noninvasivetestdetecction=ammoniuminbreath,
reeactiontoforeignmaterial.
bacteriainfeces,aabsinserum

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

Stomach,Conttinued
Gastriccongenitalano omalies
Heterotropictisssuerestsgastricsmallpatchinintestines,especiallyMeckelsdiverticulum.Bleedingfrompepticulcerationofadjacentmucossa(canmakeforconfusing gdxsincethistissueisinab
bnormallocation)
Pyloricstenosis:muscularispropriahypertrophy+edema+inflamm mation.M>F;infamilies,23wkoldinfants.Projectilenonbiliousvomiting.PEfirm,ovoidpyloricm mass.Txsurgicalmmsplittting.Inadultscanbeacqu
uiredwithcancer,seconda aryfibrosis.
Acu
utegastriculcers:
PepticUlcers
samecausesasacutega astritis.
Deepchroniclesionsmostlyassocw/H.pylorriinducedhyperchlorhydricchronicgastritis.100%o of
PepticUlcer CriticallyillICUptsstrressulcers
duodenalulcersH.pyylori,70%gastric(antral)uulcersHpylori(butonly1020%ofthoseinfectedw/H H
Happenwithseverephy ysiologic
Disease pyloridevelopulcers)).Resultfrommucosalbre each(+exposuretoacid/pepticjuices);cofactors
stressshock,sepsis,burns,trauma
(chronicNSAIDuse,ssmoking,highdosecorticosteroids,psychologicstresss).w/ZES(highgastrin
(Curlingsulcer)inpro oximal
secretionbytumorcaausesacidity)
duodenum.
98%induodenumorstomach(4:1).
intracranialinjury,su urgery,tumor
o Duodenalinaanteriorwall,nearpylorus.
(Cushingsulcer)esop phagus,
o Gastricinlesssercurve,antral,nearbody.
stomach,duodenum.
o Size<2cm.if<0.3cm,shallow;>0.6cmdeep.Single80%.Roun nded,sharpedges.Wall
Morphology:multipleabrupt
straight.Marginlevelw/mucosa.Base esmooth/clean,withblood dvessels(sometimes
lesionssmall,<1cm;ccircular.
thrombosed).Theyhaveapunchedouttappearance.
Normaladjacentmucossa.Superficial
Microscopicmorphology:
erosionsorfullthicknesssulcerations.
o Acute:surfacenecroticdebrisneutrophilinfiltrate
Black/brownbaseduettoacid
o Chronic:deep granulationtissue,deepeestscarandthickBVsaadjacentchronicgastritisiss
digestionofblood.Noscarringor
almostalwayspresent.Ulcerdepthvarie essuperficialtodeeppen netrationintowallor
thickenedbloodvesselinulcerbase.
subjacenttissuesperforationcanhapp pen.
Ulcerdifferentfrommerosionerosiondoesnntbreachmuscularismuco osa. Completelyhealindayssweeksif
Clinicalfeatures:mid ddleaged/olderadult.Epiggastricburningpainseve eralhourspostmeal,worse
NSAIDs:suppressm mucosalPgsynthesis,aspirrindirectlyirritates causeisremoved.
atnight,betterw/eatting/alkali.N/V,belching/bloating,wtloss,microcyticanemia(irondeficiency)),
Cigarettes:impairhhealing/bloodflow Tx:14%needtransfusion.Correct
evidenceofbleeding//perforation.Perforatingu ulcersmayradiatetoback,,LUQ,chest
CRF,hyperparathyrroidism:moreulcersbeca usehypercalcemiastimulaatesgastrin underlyingconditionsto otx.Bestto
Tx:eradicateHpylorii,acideffects.Surgerymmaybeneededforbleedin ng/perforationlesions
production.Nogen neticlinkstoPUD. useprophylaxistoprevent.
HypertrophicGastropathy: Gastricdilation::fromgastricoutletobstruuctionorfunctional
Gastricvaricces:
Conditionsw/giaantcerebriformrugalfoldsepithelialhyperplasiaa,noinflammation.Mimics atonyofstomacch/intestines(paralyticileuus).Canleadtogatric
Happenw/portalHTN(but
carcinomaandlymphoma. rupture.(canhaappeninnewbornduringl abor,w/severe
lessthanesoophageal
vomiting,cardiooresuscitation,afterlotsoffcarbonatedbeverage
varices.).Mostwithin23
Variants: intake.
cmofGEjun nction,rarely
acidsecre on nriskpep culcer. reallyhighhyperplasiaofparietalcellsZollingerElllison
occurwithou utesophageal
Syndrome:duettogastrinriskw/MENI(gastrinsecretedbyn nonBcelltumorofpancreaas) Phytobezoars plantmaterialconcretion inthestomachthat
varices(soyoucanavoid
acidsecre on nnoriskulcer;seccretedmucus.ReallyhighhyperplasiaofFOVEOLARcells. cantbedigestedd
doingadang gerousbiopsy
Lotsofmucus+deepglandatrophy.Happ pensw/Menetrierdisease::M>F,30s50s.duetoexccess
onthese.
TGFa.Protein/wtloss,diarrhea,riskoffadenocarcinoma. Trichobezoars hairballs
Hyperplasticpolyps(75%): Fundicglandpolypss(prevalence): Adenomas(~10%offpolyps):
G
Gastric
Hyperplasia,su urfacecells.Antrum,chronnicgastritis.Multiple,mosst Fundus,cysticglands.Singleormultiple.F,prrotonpumpinhibitors. Neoplasm,intestinallcells.Antrum,chronicgastritis.Single;<2cm.Sessileorw/stalk.
Polyps
<1cm.Sessileorw/stalk Seenw/FAP(familialadenomatouspolyposis) AllhaveDYSPLASIA((>2cm).~30%harborcarccinoma.Seenw/FAP(colon n)
A
Adenocarcinoma GIST(G
Gastrointestinalstromaltu umor) Kaposissarcoma,MALTlymph homa
Canpenetratethrougghwalltoserosa.Theyme etastasizetoregionalthendistantlymphnodes.Vircchowssupraclavicularsen ntinellymph TTumorofinterstitialcellsoofCajal(which Stomachismostcommon nsiteof
nodeisoften1stsignofmalignancy.AlsoSisterrMaryJosephnoduleofp periumbilicalregionsignofmetastaticcarcinoma(>>50%ofcases ccontrolGIperistalsis).50%
%ofthesetumors extranodallymphomas.Mostare
areGIcancers) aareinstomach. MALTlymphomas.Stomacharise
Canextendtoadjacentorgansduodenum,paancreas. AAge:peak60yrs,M>F. whereMALTisinducedb bypro
Widespreadtumorse eedingcanoccuronperitonealsurfaces MMostlysolitary,canbemulltiple.Protrude lymphomatousinfection.AllareB
Tumors: Distantmetastases:liver,lung,ovary,Krukenbe ergtumor(signetringcellcarcinomabilateralovaaries) inntolumenorserosa.Cutssurfaceistan celltype.
Gastric In
ntestinaltype:(likecolonccancer) nnowhirlingsmoothmm,heemorrhage Mostareassociatedw/chronic
Diffusetype:
D
carcinoma Histologyglandform mation,mucin.Growth/invasionbulkytumor,invaadesalongbroad ccommon. gastritis(Hpylori).
poorlydifferentiatedsingle
especiallyhigh front.Predominatesinhighgeographicalriskareas.Developsfromprecu ursorlesions,M>F. MMicroscopic:elongated,thinspindlecells Ifnotassociatedw/Hpylorithencan
dyscohesivecells(signetring).
inJapan,Chile, Mostinantrum,onle essercurvature.Grosspatttern:focallesion.Exophytticmassorulcer,flat oorplumpepithelioidcells(ormixture). begenetranslocationt(11,18),
Growth/invasiondiiffusely
CostaRica, (early). PPrognosislocation/size/m mitoticindex t(1,14),t(14,18).AllcausseNFkB
infiltrating.Noprecu
ursorlesion.
Colombia, Risk:Hpylori,diet,cu
ulinaryprocesses,lowSEsttatus,smoking ppredictaggressive.Gastricconesareless activation(promotesBce ell
NogeographicalriskM=F.Gross
China,Portugal, Genetics:FAP,othermutationsofcoloncancerassociated aaggressivethansmallintesstine. growth/survival).Antibio oticscure50%
pattern:entirestomaach.Cells
Russia,Bulgaria, RRecurrence/metastasisisu unusualif<5cm lesslikelyiftumorisadv vancedor
permeatewallinsidio ouslyinsingle
moreinlower ++raremitoses,butlikelyif>10cm+lotsof aggressive.
fileorsmallclusters.Thickwall,
SEgroups.M>F mmitoses. Morphologythickenedmucosalfolds
flattenedrugalfolds..Desmoplastic
(2:1) GGenetics:95%cKIT+(CD1117).70%are andcentralraggedulcer.Initially
responseresultsinR RIGIDWALL
CCD34+thatshowdifferen ntiatefrom involvesmucosaandsubmucosathen
(leatherbottlestom machlinitis
leeiomyoma destroyswallstructures.Microscopic
plastic)
885%havecKITorPDGFRA Abothactivate lymphocytesdenselyinfiltratelamina
Riskw/chronicpangastritis
TTKsignalingpathwaytoprromotecell propria+glandepithelium m.
(multifocalatrophyw w/intestinal
pproliferationandinhibitap poptosis Lymphoepitheliallesion gland
metaplasia),adenom mas.
TTx:imatinib(TKinhibitor usein destructionbyabnormallymphocytes.
Genetics:lossofEcaadherinfx,
uunresectable,recurrent,metastatic Cellmarkers:CD19/20+
CDH1mutation
ddisease) Youllloseperistaltic
fxobstructionperfora ate

Small/LargeIn
ntestinePathologgy
Gasstrin
VIP
Acttion:H+secre onbyparietalcells,S mulates GRP(Bombesin) Enkephalins
Action:relaxesGIsmooothmm(LES),
gro
owthofgastricmucosa HistamineActionn:directlygastricH+ Actio
on:gastrinreleasefromm Action:StimulateGIsm moothmm
pancreaticbicarbssecretion,inhibits
Stim
muli:Gcellsofantrumsecreteinresponsetoameal secretionStimulii:Mastcellsofgastric Gcells contraction(LES,pyloric,ileocecal
gastricH+secretion.
phenylalanine,tryptophan,stomachdistention,vagal mucosarelease Stim
muli:Vagusnnthat sphincters),inhibitintestinal
Stimuli:Releasedfrommneuronsin
stim
mulationmediatedbyGRP. innergateGcellsreleaseit secretionoffluid/elecctrolytes
mucosa/smoothmm ofGItract
Inh
hibition:H+instomachlummen,somatostatin

GIHormones CCK GIP Somatostatin Secretin

Peppsinogen/Pepsin
Action:Contractiono ofgallbladder,relaxationo
of Action:insulin Action:inhibits Action:WorkstoH+in nlumenofsmall
Seccretedbychiefcells
SphincterofOddi,Paancreaticenzymesecretion n, release,inhibitsH+ releaseofallGI intestinepancreaticbicarbsecretion,
toh
hydrolyzeproteins
helpsbicarbsecretion nfrompancreas,growtho of secretionbygastric hormones, growthofexocrinepan ncreas,s mulates
top
peptones.
exocrinepancreas, gastricemptying(more parietalcells inhibitsH+ water/bicarbexcretionfrromliver,bile
Stim
muli:Gastrin,Ach,
timetodigestthefatts) Stimuli:Duodenum, secretion production,inhibitsH+seecretionbygastric
seccretin
Stimuli:Icellsofduodenum/jejunumrelease jejunumreleasein Stimuli:H+in parietalcells
Cleavedtopepsinat
whentherearesmalllpeptides/AAs,FA, responsetoFA,AA, lumen Stimuli:Scellsofduoden
numreleasewhen
pH<<2
monoglyceridesNOTtriglycerides(theydont ORALglucoseload Inhibition:Vagal H+/FAinduodenallumen n

crossintestinalcellm
membranes) . stimulation
Sensorynn:ccellbodiesinnodosegangllia(vagalafferents)andspinal(DRG)ganglia.ConveyysensoryinfotoCNS
(chemo/noci//mechanoreceptors)Meissnerssubmucosalplexusscontrolssecretion/bloodflow

Entericnn:UselocalreflexestorelayinnfointheGItract.Myenteericplexus(Auerbachsplexxuscontrolsmotility)
Locatedbetw weenlongitudinalandcircu ularmmlayers.
Excitatory:Ach(intracellularCCa++tocausecontraction).
Inhibito
ory:NO(smoothmmcG GMP),VIP(smoothmmccAMP)
Parasympatheticnnexciteente ericnn
Sympattheticnninhibitentericnnn


Enteroendocrinecells:
Enterochromaffincellsinmucosaasensorydetectors,releaase5HTactat5HT3receeptorstocause
excitation/activationofmotorreflexes.
Motilin
ninitiatesMMC
Parasympath heticnn:UsuallyexcitatoryyonGItract.Vagusnnand
dpelvicnnAchisnt,stim
mulatesmotility.

Sympatheticnn:UsuallyinhibitoryonG
GItract.FibersoriginatebeetweenT8L2.Postganglioonicnninceliac/superior
mesentericgaangliaandinferiormesentericgangliaNEisnt,inhibitsmotilityandsphincctertone

**BothPNSaandSNSsalivation.

Localintestinalmotility: MigratingMoto orComplex Ileoceecalreflex:

Rectosphin nctericreflex,defecation:
Localcontracttionsexposeintestinalconttentto Cyclicpatternoofgastrointestinalmotility,severalhours controolsmovementfromsmallintestine
Gastricemptying: afterameal.Cyyclefrequency=7580min n.Actsasa coloonandpreventsrefluxofccontent Movementofcoloniccontentsintorectumdistends
enzymesandaabsorptivesurface.Tonic
coordinationofantralcontractionand housekeepertosweepstomachandcleeanupsmall backinntosmallintestine axationof
it,initiatesrreflexcontractionsandrela
contractionssseparateboluses.Peristalssis
pyloric/duodenalrelaxxationhastohappen intestineafterddigestivephase.3phases: internalanaalsphincter(externalsphin ncterhas
propelsintestinalcontractionsovershorrt
together.Reflexcontrractionofantrumis Phase1:little/nocontractileactivity(10minute voluntaryco ontrolandrelaxeswhenapppropriate)
distances
mediatedbyAch,refleexrelaxationof duration))
pylorus/duodenumism mediatedbyNO. Phase2:intermittent/irregularcontractileactivity
Sometimesdiabeticsh havedeficitsinNO (60mindduration)
containingnn,sotheyhavedelayedgastric Phase3:strong,slowlypropagatingg,startin
emptying.Evenduringgfastingcontractionseverry antrumaandgototerminalileum.P Precededbyrise
90minutesclearoutsttomach(motilinmediates)) inplasmaamotilin(initiatesMMCin
antrum/d duodenalregion)
Segmeentingcontractions:lowfrequency,
Ifthisisntworkkingwell,canhaveintestin
nalovergrowth
propellcontentslowlytoalloweenhanced
insmallintestinne.
water absorption

Massmmovements:13timesadaay,
contraactionsstopandthereissttrong
waveoofpropulsivecontraction.

Gastroocolonicreflex:feedingstimulates
coloni cmotility(mayinvolveexttrinsic

nervessofPNSaswellasCCK)

Small/LargeIn
ntestinePathologgy
Smallintestine: Mucosa:Villicrypptheight4:1.
6mlengthduodenum m Duodenum mhas
(1st25cm submucosaalBrunner
retroperitoneal),jejunum glands(seccretebicarb,
(inperitonealcavity, glycoproteins,
transitionstocolonat ppesinogen nIIlike
ileocecalvalve). pyloricmucusglands)
Columnaraabsorptive
Normal
cells(denseebrush
bordermiccrovilli,
terminalwweb)Goblet
cells(secre
etemucin)
Endocrinecells
Panethcells:eosiinophilic,
secreteantimicroobialproteins
(defensins)
Duodenum: Jejunum
m Ileum
Hypertonicfluidenterss,becomesisotonic(some
ewater Absorb::water/electrolytes(much
secretedintolumen) tubuleinkidney)
Absorb:Divalentions,Fe,watersolublevitaminss
Largeinttestine(colon):1.5m
retroperritonealinascending
anddesccendingportions
(accesso
orybloodsupplyfrom
posterio
orabdominalwall).
Functionntoreclaimluminal mucosa.Regeneratesw
water/electrolytes.
hlikeproximal
Rectum:Sigmoiddcolontransitions
Mucosa:hasnovilli,few wer
torectumarounddS3.Upper
microvilli,gobletcells,,isflat.
suppliedbysupeeriorhemorrhoidal
Hasstraighttubularcryp pts
branchofIMA.LLowersupplied
thatextendtomuscularris
byhemorrhoidallbranchofinternal
well
iliacorinternalppudendal.
(allisrenewedevery46 6
Peristalsis
santerogradeand
dayssorepairswellbu ut
retrogradeemixesfood,helps
alsoverysensitiveto
nutrientabbsorption.
radiation/chemo)
Mediated byintrinsic
Cecumascendin ng:
Meissnerpplexus(baseof
suppliedbySMA
submucosaa),extrinsic
Transverse
Auerbachpplexus(between
descendingsigmmoid:
innercircuumferetial/outer
suppliedbyIM
longitudinaalmm)
Colon
Absorb:water,Na+,Cl,K+,B
BILESALTS,IF/B12 Absorb:Water,NaCl(butmosthastobedoneinsmallintestineoritsoverwhelmed)
Seccrete:bicarb Secrete:Bicarb,K+(d
diarrhealeadstometabolicacidosis,hypokalemia)
DOESNTabsorbcarbs,fats,orproteins

Proteins: Lip
pids:
Carrbs: Pepsinogen:activatedbygastricH+ +topepsin Diggestion:
MOONOsaccharidesabsorbedinsmall Pepsinw
worksbestatpH13,denatturedif>5. Gastriclipase(chiefcells)secretedwhenstimviaaAch,gastrinoptimalatpH26.
inteestineviaNa+dependentccotransport Pancreatiicproteases(endopeptidassestrypsin, Activeinstomachandduodenum.Hydrolyzespoosition3ofTGtomakeFA A/DG
(SG
GLT1glucose,galactose),ffacilitated chymotryypsin,elastase;exopeptidaases Antralsystoleformsemulsion
difffusion(fructose) carboxypeptidaseA/B)activatedb byenterokinase
Brushborrdermembranepeptidases(aminopeptidase Absorption:
N,endopeptidases,carboxypeptidaases,dipeptidases) Acid+secretinfromScell+bicarbfrompanncreaticductpH(6.5)
4intracelllularpeptidasesdigestabssorbed FACCK(duodenaleendocrinecells)enzymeessecretedfromacinar
di/tripepttides cells/gallbladdercontracts/Oddirelaxes.
Notneededforproteindigestion,b buthelps.
AAsabsorbedinsmallintestineviaNa+dependent Bileacidsemulsifyfatsso olubleinwateratintestinaalpH,nopassiveabsorptionin
cotranspoort biliiarytract,limitedpassiveaabsorptioninsmallintestinne.Ifamidatedresistanttto
Di/Tripep
ptidesabsorbedinsmallinttestineviaH+ hyd drolysisviapancreaticenzyymes,passiveuptake.
dependen ntcotransport
Pancreaticlipaseshydrolyzzelipidstosmallerforms(FFA,monoglyceridesinacttivatedby
gastricpH).OptimumpH=89or67ifw/bilesalts..pH<4inactivateslipase.Lipases
Preegnancy:length/massofintestine, areeboundtobilesaltsviaCOOLIPASE.
lengthofvilli,numberofvilli,and
glusocseabsorption Sollubilizedinmicellesviabileeacids.Micellesformw/bbilesaltsinintestinallumenn,
Oldderagedeclineinglucose etransport, FA//monolycerides/cholestero olcandiffuseintocell,reeesterificationincellto
lesssresponsivetodietarychaanges trigglycerides/phospholipids.Chylomicronsformincell (requiresapoprotein)andare
Panncreaticamylasehydrolyyzesthe traansferredtolymph.
alpha14linkageofamylose//amylopectin Chymosinninneonateshelpsw/effectivedigestionof Sho ort/mediumchainFATGsd dontrequiremicelleform mationandlymphatictransportcan
milkprotein useeshort/medchainFAtotreatsteatorrheacausedby yfatmalabsorption.
Electrolytes: B12: CobalaminRcomplexbrrokendown
NaC Cl: Fatsolublevitamins: Theyareincorporateddinto Madeonllybymicroorgs, bypancreaticprotease,binds
Smallintestine:entersvianaglucosecotransportt,NaAAcotransport, ADEKrequireadequate micelles,takeninvia passive suppliedbbyanimalproducts cobalaminbindsIF
NaH+exchange lipidabsorptionsoany diffusionorcarriermeediated Role:coenzymeforconversionof oakeinCblIF
Carrierindistalileumto
Colon:passivediffusion
n,stimulatedbyaldosteron ne diseasethataffectsbile transport,andpackaggedinto homocystteinemethionine, complex
PumpedoutofthecellagainstECMgradientbyN NaKpump(basolateral) absorptionwillaffect chylomicronstocircu late. methylmaalonylCoAsuccinyl AbsorbedCobalaminsto oredinliver
K: these(VitAnight CoA.
Dietaryabsorbedinssmallintestineviapassived
diffusion(paracellular). blindness,VitD Sxofdef:megaloblasticanemia,
Activelysecretedincollon(stimulatedbyaldosterrone).indiarrhea osteomalacia,VitE neuropsyychabnormalities(but
becauseofflowratede ependentmechanism.Sodiarrheacanleadto hemolyticanemia,VitK youhaveyearsofstored)
hypokalemia. PTT).Pancreatic
Cl:AccompaniesNa+absorpttionpassivediffusion(paracellular),Na+/Cl lipasesremoveesters PepsinreleasesCobalaminfrom
cottransport,ClHCO3exchangge fromA/E.Thelipases food(Gasstrinaction)
SecretedintolumenviaachannelsregulatedbycA AMP,Nafollowsvibrio removeestersfromA/E. Cobalaminbindssalivary/gasticR
upregulatesthis. proteinsiinstomach
Small/LargeIn
ntestinePathologgy
Gasstroscisis Ompalocele Heterotopia
H Malrotaation Dupliication Atresiaw/obstructio on
Abd dominalwalldoesntform intestinesdontreturrntoabdominal
norrmally.9Xmoreonrtside. cavityafterphysiologgicherniation.
pancreaticor
p bowelfaailstorotate atresia=failedformaation.Faileddevelopmenttorvascularinsult
Abd dominalorgansprotrude Abdominalcontentsprotrudethrough smallorlargebowelsaccular
gastric,
g properlyybefore/during infarctresorption.InvolveSB,rarelycolon.Duodenum=
thro oughdefect.Umbilical enlargedumbilicalrinng. orelo
ongatedcysticstructures,
anywherein
a returno
ofintestinesto jejunum=ileum.Sin ngleormultiple(~10%).To otalabsenceorstring
corrdNOTpartofdefect. Coveredbyamnionssac.Intestinesalways alonggsideorincorporatedin
intestines,12 abdominalcavityin likesegment.Includesimperforatemucosaldiaphragm/imperforate
NOOamnioncovering(bathed MALROTATED. wall
cmnodule
c weeks5512+ anus.birdsbeaksiign
inaamnioticfluid). Additionalanomaliescardiac50%,
NOOadditionalanomalies. neuraltube40.Highhmortality.
HirschsprungsDiseaseCon ngenitalAganglionicMega acolon MeckelD Diverticulum
Miggrationarrest/prematuredeathofneuralcrestcellssthat Shortseggmentform(moreinMALEES)rectum+sigmoid AcquiredMegacolonocccursatany Failedin nvolutionofvitellineduct(normally
devvelopintocolonicneurona alplexuses.Ganglioncellssareabsent colon age. connectssguttoyolksac).Ariseon nanti
inttheaffecteddistalsegmentt(MeissnersandAuerbach hsplexus). Longseggment(moreinFEMALES) rectum+entirecolon Chagasdisease(losssofganglia, mesenteericsurface.
MeechunclearRETmutation nsinvolvedinallfamilialcaasesand Dx:muco osalbiopsyabsentganglioncellsindistal estroyedentericpllexuses). Ruleof22s:In2%ofpopulation,2length,within
sommesporadic.Variablepene etrance,M>F. segment.HE/immunohisotchemA AChEstains.10%of Mechanicalbowel obstruction 2ftofileeocecalvalve,2Xmorecom mmoninmales.
Unaffectedsegment:iisdilatedproximaltoobstrruction, caseshavveTrisomy21. (tumor,inflammatoorystricture) Ifsx,willbebyage2.Truediverticculum(all
normalganglia,walliniitiallyhypertrophiesthend dilates,thins, Clinical:P
Presentinneonatalperiodfailuretopass Toxicinflammationn(IBD layersoffbowelwallpresent).50% %contain
Congenital distends,mayreupture e(cecum). meconium.Progressestoobstructiveconstipation.May UC>CD),Cdiff. heteroto opictissuepancreaticorgastric(bleed).
anomalies DisstalsegmentisNOTinnervvatedcontacted,hasnogganglion haveabd dominaldistention. Visceralmyopathy Mostasxx,incidental.
cellls.Nocoordinatedcontracctionsfunctionalobstrucction.Always Complicaationssuperimposedente erocolitis, Functionalpsychossomatic Canbeco omeintussucepted,incarcerate,
invo olvesrectum fluid/elecctrolytedisturbances,perfforation/peritonitis disorder perforatte(causingbleeding)
AfterantibiotictxusuallyfromtoxinsofClostridiumdifficile(butccanhappenanytimethereisseveremucosalinjuryassinischemiccolitis,volvulus,necrotizinginfections).Acutecolitisw/anadherentlayerof
PseeudomembranousColitis inflammatoryce ells/debrisoversitesofmu ucosalinjury.
DxconfirmedbyyseeingCdifftoxininstoo ol.Relapsein25%.
Waterydiarrheaa(nowtloss),patchesofb bandlikecollagendeposits directlyunderthesurfaceepithelium.Middleaged,,olderwomen.
ColllagenousColitis
Normalradiologgic/endoscopicstudies,lym mphocytesinepithelium+mixedinflammationinlam minapropria.
Chronicwaterydiarrhea(nowtloss)w/inttraepitheliallymphocytes.AffectsM=F,associatedw w/autoimmunediseases(cceliacsprue,thyroiditis,artthritis,autoimmunegastrittis).
Lymmphocyticcolitis
Normalradiologgic/endoscopicstudies,lym mphocytesinepithelium+mixedinflammationinlam minapropria.
AIDS:50%%getdiarrhealillness,malabsorptivesymptom.Probablyduetocoexistentinffections,butproposeddireectAIDSenteropathy
Transplanntation:pretransplantconditioninginjuressmallinte estinalmucosa.AcuteGVH HDcausessevereabruptoonsetwaterydiarrhea.FoccalcryptcellAPOPTOSISseeen.Followsallogenicbonemarrow
transplanntskinandGItractaremostaffected.DonotTcellssattackagsonrecipientep pithelialcells.
MisscellaneousIntestinal DrugInducedInjury:Focalulceratio onwhenpilladherestomu ucosaandreleasesconten ntslocally(canhappenineesophagusw/dryswallows)),enterocolitisoftenassoccw/NSAIDs.
InfllammatoryDisorders RadiationnEnterocolitis:anorexia,ccramps,malabsorptivediarrrheafromacutemucosaliinjury;finallmatorycolitis maybeseenw/chronicradiationenteritis/colitis.M Mayhaveischemicfibrosis/stricture
Neutrope enicColitis(Typhilitis):acu
utedestructionofmucosaofcecalregionseeninneu utropenicpts.Impairedm mucosalimmunity+compro omisedbloodflowdamage
DiversionnColitis:divertedstreamthroughiliumdeprivesFFAsupply.Fixedw/restoredfecalflowthroughcolon,eenemasw/shortchainFA..
SolitaryR
RectalUlcerSyndrome:recctalbleeding,mucusfromanus,andsuperficialulcerrationofanteriorrectalwaall
CeliacDisease LesionSBmucosaissflattenedvillusblunting ng,atrophy.Hyperplasticccrypts,
Sensitivitytoglutenprottein(wheat,oats,barley,rrye).Chronicdisease Dx:An ntigliadinIgA,Antitissue
lymphocytesindamaagedsurfaceepithelium(vaacuoles).Laminapropriah has
impairednutrientabsorp ption.Sx/lesionimprovew w/grainwithdrawalfrom transgglutaminaseIgA,antiendo omysial(very
lymphocytes,plasmacells,eosinophils,ms,m mastcells.Damageisgreatterproximally
diet speciffic),improvew/glutenelim mination,
(duodenum).
Biopsyyidentifyclassicfeaturess,butsprue

Epi:MainlyinCaucasians(geneticpredispositionMHCIIDQ2orDQ8 likech
hangesseeninotherchang ges.Hxof
st Sx:GImalabsorption n,fatigue,wtloss,irondefficiency.Chronicdiarrhea(steatorrhea).
haplotype;inmonozyggo ctwins,1 degreerelattives.F>M,2060yo). immu unedisease,lymphocyticccolitisisaclue.
Thegreaterthelengtthofdiseasedbowel,thew worsethesx.Latentdiseasseifonlyhave
Abooveceliac,belownormal
serology,silentifnossx.
Pathogenesis:Tcellsaccu umulateinmucosa(CD8in nepithelium,CD4inlaminaa Risk:TTcelllymphoma,smallinttestinal
Infantsfailureetothrive,irritability/mm
mwasting
propria).Gliadininducessepithelialcellstosecrete eIL15activatesCD8, adeno ocarcinoma,esophagealsq quamouscell
Olderchildren::shortstature,pubertyde lay,abdominalpain,N/V,constipation,
damagescells,riskoflymphoma.tTGdeamimidatesgliadin(peptidesbind d carcinnoma.Suspectrefractoryssprue
behavioral/sinproblems
toDQ2orDQ8HLArecep ptorsonagpresentingcellss.CD4recognize or. caancerifwtandGisxarisseinspiteof
Extraintestinal:Dermatitisherpetiformiis,jointproblems,seizuress,apthrous
mucosaldamage,BcellsantitTG,antiendomysiu um,antigliadin. dietreestriction.
Malabsorption stomatitis,osteeopenia

Syndromes: TroopicalSprue Malabsorptionsyndrome eofpeoplelivingin/visitinggthetropics.Sx:onsetdayysafteracutediarrhealinfection.Bacterialovergrow wth.Rx:broadspectrumaantibiotics,maypersistforyears.NOLYMPHOMA ARISK
Clinicallysimilar,
mayneedbiopsy, (Po
ostinfectious) Morphology:likeceliacexceptlesionalsoin nvolvesdistalsmallintestin
ne(megaloblasticanemiaislikelyduetoB12lack
effectsarebody Wh hippleDisease
wide Cause:Tropherymawhip ppelii(G+actinomycete)caausesraresystemicdisease eorgproliferate/accumu ulateinanytissue(ms). Caucasian,M>>F. Sxx:malabsorption,diarrhea,wt.Arthropathy(initia alsx),
Pathogenesis:Nohostim mmunereaction,pathogenesisnotclear.GIsmallin ntestinelaminapropria+m mesentericlymphnodes lymphatic lyymphadenopathy+skinhyperpigmentation.Mayhav ve
obstructionmalabsorp ption.(especiallyfat) po olyarthritis,psych/cardiacabnormalities.(butwithth hesesx,you
Morphololgy:smallintesstinemucosalsurfaceissh haggywallthick/edemattous.Villiblunted,foamymsinlaminapropriafilleedw/PAS+,diastase w
wouldprobablythinkofMA ACorTB)
resistantgranules.Lysosomesarestuffedw/partlydigestedrodshapedbacilli.Cancauseenlargedmeesentericlymphnodes,thicckenedcardiac Dxx:PAS+foamymsinthesmallintestinalmucosa
valves Rxx:antibioticsw/promptressponse

Dissaccharidase(Lactase)Deficiency Abetalipoproteinemia
A
Infants:congenitalenzyymedeficiencyAR,rare mutationoflactaseenco odinggene Presentsininfancy(rareinb bornerrorofmetabolism)
(malabsorptionatmilkfeedingexplosive,frothyywaterystools,abdominaldistention,correct Absorptivecellsunabletos
A synthesizeortransporttrigglyceriderichlipoproteins(AR,raremutationofmicrrosomaltriglyceridetransfe erprotein
w/milkremoval) MTP).Cellsareunabletoa
M ssembleorexportchylom icrons.Triglyceridesaresttoredtheninabsorptiveceells.Appearasfat+cellvacuolesincells.
Adultsacquireddeficiency. AlllipoproteinsthatccontainapolipoproteinBw willbemissing,nochylomiccrons,VLDL,LDL.EssentialFAnotabsorpbed.Fatso olublevitamin
Wh hy?lactoseisincompletelydigested.Osmoticdiarrrhearesults.Bacteriaferm mentunabsorbed deficiencies,lipidmembranedefects(RBCacannthocytesspurcells).
suggarsleadingtoH2produ uc on(breathtestdetectss).Nohistologicalchangess. Sx:seenininfancyffailuretothrive,diarrhea, steatorrhea

Small/LargeIn
ntestinePathologgy
Complication ns:Canhave Complicaations:Toxic
CrohnsD
Disease Sx:milddiarrhea,fevver, uveitis,sacroiliitis, megacoloon(greatest
Where:ANYPARTofalimentarytract,
abdominalpaininRLLQ.
Fluid/electrolyteimbbalance+
ankylosingsppondylitis, dilationaatcecum, Sx:bloodyy,stringymucoid
diarrhea,SERIOUSbleeding.
U
UlcerativeColitiss
OveerallEtiology Smallint+rttcolonsuggestsCD>UC. migratorypolyarthritis, canbecoome W
Where:COLONONLY,spareanus,involve
Strongimmuneresponses wtloss/malnutritionn.Anemia erythemanod dosum, gangrenoous), LLQpain//crampsrelieved
Lesionsskiparound,involveanus,sparre rectum.LesionsCONTINUOUS.
againstnormalflora(to oomuch (maybebloodlossiffcolon riskGIcarcino
oma(56X). developinngcolon w/defecation.
rectum. Histo:limitedtomucosa,submucosared,
Tcellactivationortoolittle involved) Strictures,ob
bstruction cancermmorelikely Fluid/elecctrolyteimbalance.
Histo:TRANSSMURALlymphocytes, bleeeding,granular,friable.E
Earlycrypt
controlbyregulatoryT T Assocw/SMOKING mayrequirerresection thanCD
plasmacells,,lymphoidaggregates. abbscessesexpand,coalesce.Formbroad
lymphocytes) NoncaseatingGranulomas(30%). areasofulceration(canbee extensivefrom
Defectsinepithelialbarrierfx Cobblestone emucosa.Lumennarrowed d, chhronicmucosalinflammatio on/damage).
15%have1stdegreerelatives fibrosingstrictures/obstruction.Sharplly Psseudopolypsarecreatedfromislandsof
affected(9%risk) demarcatedlesions,fat remainingregeneratingmuccosa.Ulcers
Idiopathic
Butetiologyreallyunkn nown. wrapping/cre eeping. canform,merge,stopatmm m.WallisNOT
Inflammatory
Linktoimprovedhygienic Cause:Idioppathic.NOD2assoc?(may thick,serosanormal.
BowelDisease
conditions? triggerNFkB).11%pANCA+,ASCA Heealing/regenerationcanlea adtogland
Carcinomarisk:highestw/810 (antisaccharromycescerevisiaeab) disstortion,atrophy,submuco osalfibrosis.
yrscolitis,especiallyifhave Sx:Apthousulcersearly,laterdeep Dyysplasiamaydevelopovertime.
pancolitis.w/active e linearulcersthatpenetratewallsand Caause:Idiopathic.75%pANCA+
(neutrophil)disease,dyysplasia, cancausead dhesions,fistulas,sinus
primarysclerosingchollangitis. tractstoadh
herentviscus,outsideskin, Asssocw/QUITTINGsmoking
Overall,morecommon nin blindcavitiess.Canhaveperforation,
females,frequentlyonssetin perianalabsccesses. Txx:SURGERYhelpssincelesionsare
earlyteens/20s coontinuous
Tx:Surgeryttofixadhesions,butnot
curativesinccelesionsskip
Sxthaatareredflags
Rom
meCriteria:Recurrentabd
dominalpainordiscomfortt3dayspermonthinlast3
3monthsassociatedw/2+ofthese:
IBS Unintendedwtloss,feverr,severechronicdiarrhea//constipation,onsetafteraage50,FamilyHxIBD/GIca ancer,celiac
Improvesw/defecation n,Onsetassociatedw/chan
ngeinstoolfrequency,Onssetassociatedw/changein
nformofstool
disease;PastHxofcoloreectalcancer,RelevantPEfindingssuggestGIdisease,Anemia,elevatedESR,Hig ghTSH
NoormalVascularsupply3majorarterialtrunks:Celiaacartery,SMA,IMA.

Watershed(borderzo ones)atgreatestriskofischemiafromhypoperfusion natsplenicflexure(borderr Sx:mosstprobablyhaveunderlyin ngcondition
2phases:
SMA+IMA),Rectosigm moidalcolon(borderIMA+ +pudendal/iliacaa). thatpredisposesthem
Initialhypoxiccinjury(vascularcomprommise).Ischemic
Mesentericveinthrom mbosisalsocausesvascularrcompromise. EElderlyCVproblems,athe erosclerosis;
IschhemicBowel necrosis:nost
stainingorcelldetail.Mucoosalsloughing,
Leesions:dependontheinsult: MMechanicalocclusionadh hesion,
Dissease shagginess.
Transmural:fullthickn
nessw/suddenacuteocclu usion,majormesentericarteries/veins,serosacan hherniation;Hypercoagulablestate;
Reperfusioniinjury:bloodflowrestored dtohypoxic
becomenecrotictoo((ifinflammationextends,ccausesperitonitis).Arterialsharpdemarcation. TTrauma,procedures,surge ery,shock,
tissuecauseesthemostinjury.ROS,neeutrophils,
Venousgradualtrannsition.Necrosisdusky/d dull,rubbery.Hemorrhage(red/purple).Venousonlyy ddehydration,vasoconstrictivedrugs,
inflammatory ymediators,activateHIF1,NFkB,etc.See
edema.Laterseepuus.Canleadtoacuteabdo omenboardlikerigidity,(SEELECTURETOFILLIN) nodosum,
vvasculitidies(polyarthritisn
vascularconggestion,hemorrhage
Mural/mucosalinfarcctionsacuteorchronichyypoperfusion.IschemiacaaninvolveANYlevelofGI HHenochSchonlein,Wegene er

tractfromstomachtoanus.Patchy,segmental(mostly)orcontinuous.Vaariablethickness ggranulomatosis)
Ischemicstricture:vvascularunderperfusion/hyperperfusion.
OOnceyouhaveoneevent,youcan
involvementwithoutsserosalinvolvement.Cansseesamesortofchangesaaslistedintransmural. Mucosalorsuubmucosalinflammation,u ulceration
Seebloodinthelume en aalwaysextendittotransmuralwith
Vascular healingw/fibrrosis.Getobstructingstriccture.
aanotherepisode
Disorders Watershedzoonesaremostlikelysites.Clueisprior
episodeofblooodydiarrhea.
Ddxw/IBDor infection(microscopicclueisinnearby
mucosafew wersmaller/atrophicglandss+fibrosis
fromnouri shment,especiallynearth hesurface)


Anggiodysplasia
Hemorrhoids
Vasscular,nonneoplasticlesion.Malformeddilatedsm mallvenousbloodvesselsandcapillaries.Mostince ecum,rtcolon.Maybe
Variciesofannal/perianalvenoushemorrhoidalplexuses.
muultiple.Spanmucosasubmucosa.Ectaticnestsofthinwalled,tortuousBV.Coveredbythinnedmuco osa.Tendtobleed
Secondarype rsistentvenouspressurrestrainingatstoolw/co onstipation,venousstasiso ofpregnancy,
chrronic,intermittent;occult,anemia;acute,massivem mightnotbedetectablebyycolonoscopy.Inpts>60yyo.
portalHTNrrare.Inferior(externalpleexus),superior(internalpleexus).Rareinpts<30.
Patthogenesis:Mechanicalfacctors(mmcontractionand dwalldistentiondeepve esselocclusionsuperficialvesseldilation
Thinwalled,ddilatedsubmucosalvesselss.Protrudeexposedtotraumaandcanthrombose,ulcerate,
recurrentvenousoutflowobsstruction),degenerative(m mostlyinpeople>50yr=vvesselweakenedovertime e),congenitalpredispositio
on
fissure,bleed,,strangulate,infarct
(seeenw/otheranomalies).Ce ecum(rtcolonhasgreattestdiameter/walltension n,sothiswhereweseemo ostofthese).
Divverticula:acquiredoutpoucching~50%inwesternadults>60yrs.Mucosaonlynomm.MostlyinLcolon(0.51cm).Areasofph hysiologicalwallweakness
Mostcases:asx,discoveredincidentally.20% %haveintermittentcramps,discomfort,
(whhereBV,nervespenetratebetweentaeniaecoli).+h highluminalpressure.Exaggeratedperistalsis(mmh hypertrophied,lowfiberdietstoolbulk).See
Diverticular distention,sensatioonofnotemptyingrectum m.Constipation,diarrhea.Minimal
outtpouchedmucosaw/fibrossis,NOmuscularis.
Disease massive).Mostwillregresssifearlyindietaryfiberr.Cancause
bloodloss(rarelym
Divverticulitis:initiatedbyobsstruction(fecalith)thatmigghtleadtoperforation.Inflammationextendstoadjjacentmucosa,pericolicfaat,maycausefibrosis,
obstructionrequiringsurgery.
striicturedlumen,obstruction n(requiressurgery).Mimiccscarcinoma.Infectioncanleadtoformationofabsccessorsinustract,peritonitis.

Small/LargeIn
ntestinePathologgy
Herrnias Adhesions(#1in nUS) Volvulus
Intusssusception
Weeakness/defectofperitonealcavitywall,mostly Fibrousbandsbeetweenareasof Completetwistingofbowwelloop
Intesttinalsegmenttelescopesintoimmediatelydistal
antteriorlyinguinal/femoralcanals,umbilicus,surgical inflammation(frromprior arounditsmesentericvasscular
segmeent.Mesentericvascularssupplypulledalongand
scars,LigamentofTrietz. surgery,endomeetriosis, attachmentbase.Leadstoobstruction
canleeadtoinfarction.
Serrosalinedherniasacprotruudesintothedefect,then infection).From
mbowelto andinfarction.
Infanttsnoanatomicdefectp pointoftractionmight
viscceralsegmentsfollow.Smmallbowel>largebowel> bowel,bowelto owall.Bowel Adultsoccursinsigmoid
dcolon
beinfflammation.Mayreducew w/bariumenema
Intestinal ommentum. loopscanslidethroughand Childrenassocw/malrootaionseen
Adultsspointoftractionismasss/tumortxissurgery
Obstruction Commplications becomestrangulated insmallintestine
Sxvomiting, Incarceration(permanententrapment)
constipation,abd
pain/distension entrapmentpressureim mpairsvenoustissue Directherniamedialtoinferiorepigastricvesselsw when
drainagestasis,edematissueswelling. abdominalcontentsgo othroughexternalinguinalringg.
visceralbulkcausespermanenttrapping. Adultonset,entersthrroughHesselbachtriangle(weaak
Bowelobstruction(obsstructivesx) pointinabdominalwallfascia)
Indirecthernialateraaltoinferiorepigastricvesselsw
when
Strangulation(compro omiseofmesentericaa abdominalcontentsgo othroughdeepinguinalring.C Covered
supplyandvenousdraiinage).Mayleadto byinternalspermaticffascia,congenitalonset
infarction

Nonneoplastic(NOmalignan ntpotential)abnormalm maturation,architecture
Hamartomouspolyps:focalmalformationsoflaminapropriaandglands.Donthavemalignantpottentialontheirown(but riskifseenw/adenomass)
Hypperplasticpolyps:usuallyffoundincidentally,atolderr
Juvenilepolyp: Hamartomasmay In
nflammatory
agee.Grosssmallmucosalp protrusions.Multipleor
13cm,pt<5yo.Rou und,smooth, beinman nyorgans riskofcarcinoma(GI,pancreas,breast,lung, polyps:
singgle(<0.5cm).Microscopiccabnormalmaturation. PuetzJeghe ersPolyp:
lobulated,stalked.Cystically (GI,muco ocut). gonads,urinogenital).Inttestinalhamartonas+ Ly
ymphoid
Dellayedsheddingofmatureccells.Accumulationofold,, arborizingn networkofglands, Cronkhite
dilatedglands.Nommalig riskofcarcinoma adenomascanleadtoade enocarcinoma. (n
normalvariant
nottneocells.Nomalignantp potential.Leadstocell laminaprop pria,smoothmm,CT. Canada:
potential. (breast,ffollicular bumps
cro
owding,infoldinginmaturesurfaceglands.Ddx Ifmultiple,alwaysasyndrome. GIhamartomas,
Singlesporaddiccases. thyroid, in
ntramucosal
w/ssessileserratedadenomas(dontwanttomissthese). Occurthrou ughoutGItract. ectodermal
80%inrectumpresent endomettrial) ly
ymphoid
Wh hiteglandsonsurfaceONLY Y. Alwaysinsm mallintestine.Riskof abnormalities,
w/bleedingretention nodules)
intussuscep ptions.Maybein nocancerrisk
polyps.
stomachan ndcolon.Pigment (anotherpolyp
Multipleparttofjuvenile
seenmucoccutaneously syndrome)
polyposissyndrome
(periorificiaalskin,buccalmucosa,
Rectal/colonhamartomas+
palmsofhaands,genitalskin).
adenomasmayyleadto
adenocarcinom ma.
Neo oplastic(precursorstocarrcinoma).Newcellproliferationanddysplasia.
Maalignantpotential:dependsonsize: Villousadenom ma:large(10cm),sessilee,shaggiersurface,13cmabove
Adenomatouspolyp: adjacentmucosa.Intramucosalcarcinom ma:glandsbreachbasemen ntmembrane
<1cmrisk,>4cm risk.
DARKglandsswithtoomanynucleion butdontinvaddemmucosae
Highgradedysplasiaofftenfoundinvillous
surface.Epithelialneoplasms. Ex:Sessiileserratedadenoma:whiitemucincontainingglandsfromdeep
(shaggy)areas.
Gland,cellp proliferationw/dysplasia.
Polyps: AnyadenomatouspolyyprequiresCOMPLETE osurface,NOnuclearchanges.Lookslikelargehyperplasticpolyp.
cryptsto
epithelialmasses
Precursorstoinvasive Associatedw/mismatchrepairmuttationintumors(especially yHNPCCofrt
removalpotentiallyh harborcarcinoma!
thatprotrude adenocarcinoma. colon)
o Pedunculatedpolypectomymightbe
fromthemucosa pedun nculated(w/stalk)or
adequate.Decidetoresectfurther
sessile
e(nostalkvelvety
dependingonstaalkinvasion,blood Adenoma:Sx:asx(usuaally).
surfaccelooksraspberrylike).
vesselinvolveme ent,andinvasionnear Mayhaveanemia,occuult
Tubulaaradenoma:small,
resectionmargin n. bleeding.Largevillous polyps
Surveillanceiskeytodettect pedun nculated,smoothsurface
o Sessileglandsiinvadesubmucosano maycauserectalbleed ing,
beforemalignanttransfo ormation! Villou slarge,shaggysurface,
stalktoactasbu
uffer.Polypectomy mucushypersecretion
sessile
e
mightnotbeeno ough. w/protein/K+loss.
FAP(FamilialAdenom matous AttenuuatedFAP:<100
polyps.Presentslaterinlife Inrightcollon,
Polyposis) HNPCC(HereditaryNonpo olyposis
(50yo)),50%cancer. mucinous//signetringcell
Adenomatouspolypossiscoli(APC ColorectalCancer)
MUTYH Hgenemutationin type,poorrlydifferentiated.
gene)mutation. riskcolorectal+extraintes nal
<10%.DNAmismatch Tumorlym mphocyte
1002500polyps.Anytypeof carcinomas.NopolyposisBUThave
infiltrates. OthherthingsthatGiveElevateedRiskofColonCancer
adenomatypicalad denocarcinoma. repair.Mayhavesessile polypsofanytype.Carcin nomasat
edadenomas Juvenilepolyposis(pressent<5yo)
Colon,otherGitractsiites.Presentsin serrate earlieragethansporadictumors
FammilialSyndromes mucinoousadenocarcinoma. MULTIPLE coloncancers PeutzJegher(present~~15yo)
teens,100%progresstocancerby (throughmicrosatelliteinsstability

30.Prophylacticcolecctomy. pathwayfrommutationsinDNA

Turcotsyndromme(CNS MISMATCHREPAIRGENESS)
tumors), Precursorlesion=seessile
Gardnersyndro ome(bone, seratedadenomas,presents
desmoidstumorrs,dental <40yo.
abnormalities)

Small/LargeIn
ntestinePathologgy
#1malignancyisadenocarcinomaa.Mostcolorectalcancerssdevelopsporadically. Pathogenesis: SttagingofColorectalCanceer
Mosta ariseinpolyps.Peakage66080.Youngeragethinkkulcerativecolitisor APC/Bcatenin npathway:localizedepitheelialproliferation
syndrome. smalladenomaasinvasivecancers.DuuetolossofAPC
Risk:
w/fiber,refinedCH HO/fat,transittime,antioxidantactivity, gene(tumorsu uppressorgene,gatekeepeerforBcatenin
bilesaltcontact.w/ASA,NSAIDSbyinhibitingCOX2neededforPGE2that mutationsofA APCin80%ofsporadicca)
promotescellproliferationafterinjury,coloncancerriskk.COX2inhibitorusedas o KRASm mostfrequentlyactivated oncogenein
FAPpro ophylaxis! adenommatous/colonca.Mutated in<10%adenomas
Gross:mostaresingle,maydirecctlyextendtoadjacentstru uctures(lymphnodes,liverr, <1cmsizze,in~50%adenomas>1ccm,~50%of
lungs,b
bones,brain). carcenomas.
Collorectal Proximal,rtcolon(oftene
P xophytic,bulky.Tendnottocauseobstructionsee e o Tumorssuppressors:SMAD:lackoofSMAD4GI
Adeenocarcinoma fatigue,weakness,irondef
f ficiencyanemia); tumors,SMAD2,APC,p53(in70880%ofcoloncancers
Distal,left(napkinringe
D encircle,constrictulcerated,infiltrativetendto suggesstedlateincoloncarcinogeenesis)
causeobstructionbleedi
c ngmelena,bowelhabitch hanges) o Telomerrase:stabilizeschromosom meactivityin
Prognosis:dependsondep
P pthofinvasion.Worseifin nmuscularispropria. coloncaa.
Lymphnodeinvolvementa
L alsoworse.Intestines/colo ondrainviaportalveinto Microsatelliteinstabilitypathway:GeneeticlesionsinDNA
liver.DistalrectumandannusareNOTdrainedviaportalcirculation. mismatchrepaairgenes.Doesnthavecleearlyidentifiable
Sameh histologygenerallywhethe errtorleftcolon.Welldifferentiatedglandsto morphologicco orrelates.MSH2,MLHSDN NAmismatchrepair
undiffeerentiatedpossible.Mucin ninglands,cells.Intheinterstium(aidstumor genesallowhigghmutationrates.TGFB,,BAXtumor
dissecttionthroughwall).Invasioncausesastrongdesmopllasticstromalreactionthatt suppressorsinactivated.BRAFoncogeneeactivated.
causeshardnessofthewall Generallyslowprogressing,screeningshouldppreventmostcases!!!

AnalCanalCarcinom
ma
Carcinomasresemblenativeepithelium/mixtuures:
Upper:Normallyhascolumnarglandular rectalepithelium.GetsADENOCARCINOMA
Middle:Normaallyhastransitionalepitheelium.GetsPureBASALOID
D(frombasaltransitionalccelllayer)
Lower:Normallyhasstratifiedsquamoussepithelium.GetsSQUAM MOUSCELLCARCINOMA.P PureisHPVrelated(w/condyloma
accuminatapreecursorsowartsfirst)

Tumors Carrcinoidtumors GaastrointestinalLymphomaa

Neu uroendocrinetumorsarisefrommucosalendocrine ecells.Resemblecarcinom
masbutmayshowlessagggressivebehavior. mphoma:Spruelikeillness,,enteropathy
IntestinalTcelllym
PreedominantsiteGItract/lu ung.MostcommonGIsite esappendixandsmallinttestine.GIcolon,rectum
m,pancreas, 3040yrs,Hx
associated.Arisesinsmallintestineadults3
stomach,biliarytree,liver.Se ecretebioactivesubstance es,maycausecarcinoidsyn
ndrome.Appearspaleyellow.Difficultto GItractisMOSTCOMMONSITEofextranodal ofmalabsorptionsyyndromefor1020yrs.Pro ognosispoor
preedictmalignantbehavior.D Dependonsiteoforigin(raarelymetastasizefromapp pendix,rectum,usuallydofromsmall lyymphomas. (11%5yrsurvival).
inteestine).Aggressivegrowth hhighdepthofpenetration;especiallybeyondmusscularispropria. Lymphomamorpholoogy:variablediffuse MALTlymphoma:ccanariseinPeyerspatchessbutmost
Gross:Solitary(inappe endix,colon,rectum),multticentre(insmallintestine,stomach).Muralorsubm mucosal,haveintact mucosal/muralinfilattrationw/thickening.Can n ariseinareasw/outtmaleinducedinstomacch.Different
overlyingmucosa.Cutsurfaceissolid,yellow.In nvasioncauseswallfirmnesss,smallbowelkinking(causingobstruction). havepolypoidprotruddinglesion,fungating fromnodallymphom masactlikefocaltumorssearly,
<2cmsizeinmostsize,tendtobelarger(3cm)in ncolon. ulceratedmass,disse minatedserosalnodules. resectable.RelapseecanbeconfinedtoGItracct.ExpressB
Microscopy:neurosecrretorygranules(densecore e).Monotonouscellsinne
ests,islands,trabeculae,accini.Nucleiare Sx:canhaveobstructtion,perforation.Can cellmarkers(CD19,20)butNOTthose(CD5,1 10)expressed
st
uniform,blandround/oval,w/stippledchrom matin.Scant,amphophilicccytoplasm.Seedensecore egranulesonEM. destroymmpropriaaandcausemotilityproblem ms innodallymphomass.Chemotxmaybecome1 tx.
StainschromograninA A,synaptophysin,neuronsspecificenolase (therebycausingsecoondaryobstruction).Duetto o ypical
Earlylesion:lyphoepitheliallesionaty
Clinicallyasx.Maybe esxifkinkedsmallintestin
ne(bowelobstruction),pain/wtloss/bleeding(esplaargecarcinoidsof lackofstromalsuppoort,largetumorsmay lymphocytesinfiltratemucosa.Glandsareeffacedor
colon),carcinoidsyndro ome(<10%casesduetopresenceofactivesecretoryyproductsinsystemicbloo od))5HT, perforate(especially afterchemotumorbullk) destroyed.Lyymphoidtissueexpands.M Monoclonality
histamine,bradykinin,kallikrinin.Willbeabletodetecthigh5HIAAinurin ne(becauseithasbeendeggradedtothis Bcell(95%) indicatesmalignancy.
metabolitebytheliver)However,ifintheRECTU UM,theydontusuallysecrrete5HT(sourinary5HIAA Awillbelow) o mostcommon areMALTlymphomas#11
Syndromefeaturesarerelatedto5HTdeliveredttosystemicbloodsignofmetastasisbecauseitavoidsinactivationin siteisstomach..Manya/wchronicHpylo ori
theliver.GIlocalizedtumorsshouldnthavethessesx.Seeblood/urine5HT.Skinflushing,bronchoconstriction, gastritiscureddbyantibiotics.Othersa//w
cramping,D/N/V,Righttsidedvalvularheartdiseaase(causesdeathin50% endocardialfibrosis). cytogenetictra nslocations.Bothactivatee
Bestprognosisinnon nmetastatictumorsofapp pendix,rectum.Deathdue etowidespreaddisease,livverfailure,carcinoid NFkB(Bcell survival/prolifera on)
heartdisease,bowelob bstruction/perforation,ble eeding o 2ndmostcomm monDiffuseLargeBcell o Laterlesion: mixofmalignantlymphocy ytes
lymphoma(EBV V+)immunodeficiency expands,repllaces,destroyslargeareasoftissue.
associated:trannsplantpts,HIV,Burkitts
lymphoma(Afrrican/endemic,sporadic,
HIV)

Uncommontumorsite,mo
U ostlybenign. Malignant:
o Epithelial:Adenomas(25%)AmpullaofVaterr(3060yo,similarto o Adenocarcinomamostlyinduodennum.Age4070.Encirclin ngorexophytictumors.Ob N/V,wtloss.
bstructingsxcramping,N
SmallIntestine colonicadenomas);Hamartomatouspolyps;In nflammatory,lymphoid Mostare
Jaundice((ampullarytumors),occulttbloodloss.Pointoftractiionforbowel(canrarelycauseintussusceptions).M
Tum
mors polyps. sporadicw
w/nopredisposingconditioons.Riskw/chronicinflam mmation(Crohns,Celiac).LLesscommonlyinherited(F FAP,HNPCC,
o Mesenchymal:GIST(gastrointestinalstromaltumorsbenignor PeutzJegher)
malignantbehavior);lipomas;neuromatoustuumors;angiomas o Carcinoidtumors;lymphomas;sarcoomas

Appendix
67cmlength,anchoredbymesentericexte ensionfromileum.Nokn nownfx.Richlymphoidtisssueinmucosa/submucossa(formsgerminalfollicless,lymphoidpulpinyoungpeople).
Normal
N
Progressiveatrop phyovertime.
Mostcommonacuteabdominalsurgicalcondition Psoassign:eextendingrightlegathipm makespsoasmmcontractorhavingptraisingthigha againstyour
5080%due etoobstruction(fecalith).Canalsobeduetogallstone, handifthiismovementispainful,ind dicatesappendicitis
tumor,ballofworms.Suppurativeinfflammation,edema. Rovsingssiggn:paininRLQwhenpressdowninLLQifappendicitis
AcuteAppendicitis
A Ptisteen/youngadult,anyage,M>F.Lifetimerisk7%. Obturatorssign:Rhypogastricpainwh henlegrotatedinternallyaathipifappendixisinflame
ed
Morphologytheprogression: Cutaneoushhyperesthesia:localizedpaaininall/partofRLQonth heskinofthearea
o Earlyyacuteappendicitis:dull,ggranularredmembrane Thinggsthatmimicit:
fibrin
nopurulentreactionoverse erosa o MesentericlymphadenitissecondarytoenterocolittiscausedbyYersiniaorav virus
o Acute esuppurativeappendicitiss:abscessformswithintheewall, o Systemicviralinfection,aacutesalpingitis,ectopicprregnancy,mittelschmerz,ccysticfibrosis,
ulcerations,fociofsuppurativenecrosisinthemucosa Meckeldiverticulitis.
o Acute egangrenousappendicitiss:largeareasofhemorrhaggicgreen Dx:mmustfindneutrophilsinmuscularispropriatodxacuteappendicitis.(butcanalsoseethis
ulcerationofmucosa,greenblaackgangrenousnecrosisth hrough w/alim mentarytractinfectionssoevidenceofmuscularwaallinflammationneededfo ordx).20
thewwallserosa.Leadstorup pture,suppurativeperiton nitis. 25%FFPdxestimatedbutthou ughtthatdiscomfortofexp ploratorysurgeryisworthtthe2%
Sx:Periumb bilicalpaintoRLQ.N/V,,abdominaltenderness.M Mildfever, morbiidity/mortalityassociatedw/perforationandcomplicationsthrombosisofpo ortalvenous
WBCelevattedto5,00020,000. drainaage,liverabscess,bacteremia.
Carcinoidtu umor(mostcommon),usu uallydiscoveredincidentallyduringsurgery/whenexaaminingresectedappendixx.Indistaltip(23cm
bulbousswelling).
Adenocarcinoid(gobletcell):typicalccarcinoidpatternw/mucinvacuolecontainingcells.
Tumors
T Mucocele:d dilatedappendixfilledw/mmucin.Canbecausedbym mucinousadenocarcinomaa
PseudomyxxomaPeritonei:abdomenisfilledw/semisolidmucin nfromcontinuedcellularpproliferation/mucinsecretiionfrommucocele.Can
holdinchecckw/debulkingprocedure esbuteventuallyislikelyfatal.
Peritoneum
Inflammation:PPeritonitismaybefrombaacterial Generallyfromruptureoffiscusore erosionthroughaviscus.CCausesappendicitis,ruptturedpepticulcer,cholecyystitis,diverticulitis,strangu
ulatedbowel,acutesalpingitis,
PeritonealIn
nfection abdominaaltrauma,peritonealdialyssis.
invasionorchemicalirritation.
Organismss:justaboutanythingEccoli,a/bhemolyticstrep,Sttaphaureus,enterococci, G,Clostridiumperfringenns.Cangetgonococcus/Ch hlamydiafromgynecologicinfections
Mostcommon:
Morpholo ogy:
o sterileperritonitis(leakedbile/pancrreatic
24hourspostinitiation,perittonealsurfacelosesitsgraay/glisteningquality.Accum
mulateserous/turbidfluidd.
enzymes),
Lateer>creamy/suppurativeffluid,maybecomethick,plastic,inspissated
o Perforated/rupturedbiliarysystem(usually
Mayyhealspontaneouslyorw//tx:Possibleresults:
w/bacteriialsuperinfection),
o Exudatesresolvesw/no ofibrosis,
o Acutehem morrhagicpancreatitis(freefat,
o Residualwalledoffabsccessespersistandmaybefociforfutureinfection,
chalkywhhiteprecipitates,bacteria
o Exudatesmayorganizeandformadhesions)
permeatin ngbowelwall),
o Surgery(fforeignmatterleadtoreacctions), Fibrousovvergrowthofretroperitone ealtissues,mayinvolvetheemesentery.Causeobscuure(mayberelatedtometh hysergideergotderivativeformigraine,surgeryhx,radiationtx).
Sclerosing
o Gynecologgicalconditions(endometrriosis, Possiblyautoimmune/systemicorigin.
Retroperitonnitis
ruptureddermoidcysts) Sortofananalogofdesmoidtumor..
Cancomefromlymphaticchannels,pinchedoffentericdiverticulaoffdevelopingforeguut/hindgut,fromurogenitaalridge/derivatives,fromw wing
walledoffinfections/follow
MesentericC
Cysts
pancreatittis,malignantorigin.Cansseemtobeabdominalmasssesandcausedxconfusioon
Tumors Virtu
uallyallmalignant
Primary:Rare
o Mesotheliomas:ffrommesothelium.Verypoorprognosis.Associatedw/asbestosexposurein80%.Oftenneedimmunoh histochemicalstainstodiffe
ferentiatefromadenocarciinoma
o Desmoplasticsma wnpathogenesis.MayberrelatedtoEwingsarcoma,rhabdoidmyosarcoma,prrimitiveneuroectodermalttumor.T(11;22),(p13;q12))translocationEWSWT1fusion
allroundcelltumor:rare,fromperitoneum.Unknow
Secondary:prettycomm moncanhavemetastaticseeding,penetrationintoserosalmembrane

Liver/BiliaryTract
Surgicaalfunctionalorganization::8segmentscaudatelob beissegmentI,therestmoovefromLRacrosstheliiver(eachhasindependen ntvascular/biliarypedicle,v
venous
drainagge).Bloodsupply:25%offCOviaportalveinandhepaticarteryviahilum.Wtt:14001600gm
BasicM
MicroscopicMorphologyo oftheLiver:
Hepatocyte:bathedinsinu
H usoidalblood(mixtureofp portalandarterialblood),ddrainsthroughfenestrationsinhepaticveins.Canm
make~500biochemicalrxnss,can
synthesize150proteins!
s
BileSystem:Bilecanallicul
B iCanalsofHerringB BileDucts(intraandextrahhepatic)
SpaceofDisse:containsfa
S atcontaining/VitArichstellatecells.Plasmaderivedd,drainsintothelymphaticcsystem.
Kupffercell:partofRESsy
K ystem,onendothelialcellsside.
Liveracini:Zone1(nearpo
L ortaltriad)=bestbloodsup pply,Zone3(nearhepatic vein)
Normallytheliversurface
N appearsamahoganybrow wn
Norma alLiverFunctions
Uses,supplies,storesalot
U t:
o Energymetabolism::Glucoseconsumption(glyycolysis)production(GNG))/Bloodsugarcontrol;Glyccogensynthesis,FAsynthesis:energystorage;FAoxidation,TCA
cycle,ATPProductioon
o Substrateinterconversion,clearance:Bilirubin nconjugation,clearance;CCholesterolsynthesis,TGsynthesis;ExportVLDL,preHDL;uptakechylomicronrremnants,LDL,
HDL;BileAcidSynthesis:solubilizationandupttakeoffat/fatsolublevitam mins;Aminoacidsynthesiss,interconversion,deamin
nation,ammoniafixation;D Drug,toxin
detoxification,andcclearance;Damagedcells,b bacteria,clearance
o Proteinsynthesis(90%ofallplasmaproteinsinbody):Albumin,clottinggfactors,bindingproteinss,aLP
Liverzo
ones
Periportal:aroundthepor
P rtaltriad(1)highlyoxygenatedbloodflowsfromheepaticartery/portalvein,travelstocentralvein.
Sinusoids:(2)midzonal
S
Vein/central:aroundcentr
V ralvein(3)willbeatriskofinjuryviatoxins,moostproblemsfromlowerpeerfusionofblood
Disorganizationofthissyst
D temwillimpairfxofliver

LiverFunctionTests(tthetrueonesarebilirubin,PTT,Albumin,Ammonia thesearedirectlymeasurringthefunctionoftheliveer)
Aminotransferases: AlkalinePhossphatase: GammaGlutamyl Albuminisan Prothrom mbintime Ammonia: metabolized
AST(SGOT)inm manyorgans,synthesizedin nhepatocytecytosoland inmannytissues,especiallybone,liverAPfromcanalicular Transpeptidase(GG GTP): indicatorofliverfx(~ allcoaggulation highinsevere
byliverh
mitochondria membrrane,bileductepithelium. occursinmanytissuues(BUT 10g/dayis factorsmmadeby dysfx(Reyees,cirrhosis),
ALT(SGPT)ismo orespecifictoliver,synthe
esizedincytosolonly Hallmaarkdisproportionate(toASST/ALT)APriseincholestassis NOTINBONE).Induucibleby synthesizedand liver,excceptfactor portalsystemic
reflecthepatocyteinjury/leakage,poorcorrelationw/histologicaldamageor duetosecre on,notreten on n.Riselagsa eracute ETOHandotherdruugs,mayrise secreted,w/T=20 8.Goodindicator shunting
prognosis obstruction,sincemustbesynthe esized,falllagsafterrelief 2.5Xupperlimitofnnormal>AP. days. formoniitoring
50100Xupperlimitofnormalinacutehepatitis,especiallyinfulmin nant ofobsttructionsinceT=1wk.A
APcannotdifferentiate UsedtoassessacuteeETOH Hypoalbu uminemiaalso acuteliverfailure BUNinccirrhosis
hepatitis,ischem
mia,acutebileductobstrucction betwee enintrahepaticandextrahhepaticcholestasis.Maybee intake(butnotvery
yreliable). fromextrrahepatic becauseofshort
25XupperlimittofnormalinETOHliverdiiseaseandmostotherchro onicliver highw/normalbilirubin(focallessionsgranulomata, Cholestasisstrongly
ysuggestedif factors(loowintake T. eflectshepatic
Bilirubinre
diseases tumorss),Morereflectsbilirubine
excretionthanAPsynthesiss. APandGGTPareeleevated.As and/or lossrenal, clearance/excretion
UsuallyAST/ALTT<1;inETOHhepatitisofte en>2;pyridoxine,oftendeficientin Cholestasislikelyifnormalaminootransferases.AP23X withAP,cannotdiffe
ferentiate gut). also.
alcoholism,isco
ofactorforboth,ASThash higheraffinityforitthanALT,thus upperlimitofnormal+highamin notransferasesisnon intrafromextrahepaatic
ALT=ra o specificc. cholestasis.
Test Resultw/hepatocelllularinjury Resultw/cholestasiss/infiltration
Bilirubin 130XULN 130XULN Constructionalapraxia:lo ossofspatialplanning(clocckdrawingabnormality) canindicatemildencephaalopathy
Lactuloseusedw/elevattedprotein
ALT/AST 5100XULN 15XULN

AP/GGTP 110XULN 130XULN
MELD(ModelforEndStaageLiverDisease)
Albumin insubacute/chronic Usuallynormal
o Predictsmorttalityin3monthsbasedonnserumbilirubin,creatinin ne,PT(INR).ascorefromm040where40indicatesttheptwill
Prothrombintime inseveredisease,nofallaftervitK Oftenhigh,correcteedafterparenteralVit
certainlydie,102027%willdie,andd<10indicatesonly4%will).
supplementation K o Alsopredictsoperativerisk(MELD>8inndicatesatleast44%comp plicationrate;MELD<8ind dicates10%orlesscompliccationrate)
UltrasoundorCTscaan Normalbiliarytractifextrahepaticobstructio on Dilatedbileducts o MayreplaceChildsclassification.
ERCP Normal Dilatedductsifextrahepaticobstruction
ImportantinDx: o GGTP,alkalin nephosphatasewithoutottherabnormalitiespointto omorefocalproblem
PtHx:Modeofonset,knownliverdisease,assocciatedsx/diseases,exposurrehx(travel,alcoholintake einUSblood o Enzymeelevaationsthemselvesarentgooodatpredictinghowseveereliverproblemsare/willlbecome
transfusionbefore19992HepC,sharedneedless/bodyfluids),drugs(dietarysupplements),recent upperGIsurgery,GI o Nogoodtestbeyondbiopsytotellcirrhhosisvsnoncirrhoticconditions,noreliableimaging
bleed(hematemesis,m melenaesophagealvarice esseenw/cirrhosis).

Liver/BiliaryTract
DeggenerationandIntracellullaraccumulation
Hepatocytesswellfrom mtoxicorimmunologicacccumulation
Triglyceridefatdroplettsmayaccumulateinhepatocytes
Patternsof (Steatosis)canbemiccrovascular(asseeninpre egnancy,fatty
Injury liver,valproicacidtoxiccity)ormacrovascular(NAFLDnon
alcoholicfattyliverdise
easeincreasinglycommonmetabolic
syndrome)
Copperorironmayacccumulateinhepatocytes
Cauuses:after8090%lossofccapacity.Concurrentstresssmayprecipitatefailure(G
failure,majorsurgery)
Causesofacuteliverfa ailure:
o Massivenecrosiss:Drugs/toxins(38%acetaminopheninUS,Carbonte
A/B)
o Noovertnecrosiishepatocytedysfxw/no onnecroticcells:Reyessyn ndrome,fattyliverofpregn nancy,
HepaticFailure
tetracycline
CausesofChronicLiverfailure:Progressivechron nicliverdisease(mostcom mmoncauseofliverfailure)via
cirrhosis(alcohol60% %,hepatitis10%,biliary10%,cryptogenic15%).
o PEsignsjaundicce(maynotseeuntilbilirubin>3mg/dL,maymissw
telangiectasis,paalmarerythema(duetoloccalvasodilation),whitenails,gynecomastia,atrophicctestes,
hepatomegaly(m maybeabsentincirrhosis)
Difffuseprogressivechanges bridgingfibrosis(scarringg),Parenchymal
noddules(regeneration),architectural(BV)reorganizatio on
Cauuses:alcoholabuse,nonalcoholicfattyliverdisease,,viralhepatitis,biliary
diseeases,hemochromatosis/h hemosiderosis
Patthogenesis:
Cirrhosis Stellatecellactivationcausesprogressivefibrosiscellproliferation,
reallyextracellularm matrixsecretion,reallyccollagensynthesis.
Phenotypechangesliipocytetomyofibroblastw w/contractile
properties;vascularresistanceportalHTN duetocytokines
producedbymanydifferentcells:Kupffer,inflam mmatory,epithelial,
hepatic,bileductalsooECMdisruption,directto oxineffect
PortalHypertension
Causes:resistancettobloodflowthroughtheportalvein:
Prehepatic:porrtalveinthrombosis,massiivesplenomegaly
Posthepatic:rigghtsidedCHF,constrictivepericarditis,hepaticveino obstruction
o Intrahepaatic:cirrhosis(mostcases),severediffuse(fattyliver,schistosomiasis,sarcoido
o Incirrhossisresistancetoportalbloodflowinsinusoids;m morebloodflowintoportaal
venoussyystemfromeffectofhepaticfailureonsplanchnicartteries(dilatedduetoaction
o Complicattions:Ascites(accumulatio onofserousperitonealfluiid),portosystemicshunts
(esophageealvarices,bleeding),conggestivesplenomegaly(hype ersplenism,cytopenias),he epatic
encephalo opathy(bloodammoniaa)
Sx:splenomegaly,ascites,caputmedusa,hemorrhoids,pedaledemaa
BileSaltsandabsoorption:
Necrosissandapoptosis:Canbedu uetoanysignificantinsult.
Fibrosis(Cirrhosis):Respoonsetoinflammationordiirecttoxicinsult.Generally yirreversible,
Zoonaldistribution:Ischemicanddrugscausecentrilob bular,Eclampsiacauses
butrecentevidenceindiccatessometimesreversiblee.Subdividesliverintonod dulesof
ce
entrilobularandmidzonal,Butmostinjuriesareacrosssallzones(periportal,
proliferatinghepatocytesssurroundedbyscartissuee.DeathofhepatocytesECM
midzonal,centrilobular)
deposition,vascularreorgganizationtothedetrimen ntofreperfusionofhepatocytes
Inflammation:Influxofacutteorchronicinflammatoryycells(Hepatitisex
CollagenisdepositedintoospaceofDisselosefen nestrations,shuntingthrou ughscar
geenerallycauseselevateden nzymes)
venouspressure.Thisisaallduetoactivationofstelllatecells(becomemyofibrroblasts,
Reegeneration:Aslongasstrructuralarchitecturestaysintact,generallyis
KupffercellshelpmakethhishappenbyreleasingchemokineslikePDGF,TNF).
co
ompleteevenwithmassive eresectionornecrosis
GIbleeding,systemicinfecction,heart Clinicalfeattures:lowalbuminemia,loowclottingfactors(coagulopathy).bilirubinemia(jaundice)+ammonemia+
estrogenem mia+portalbloodshun ng(varices/bleeding,feto orhepa cus).Pa entsareatriskofotherorgansystemfailure
(Generallyttherearefewmorphologicctissueabnormalitiesinth heseorgans)
etrachloride,mushrooms,Hepatitis Disturbancesinconsciousness((encephalopathy)CNS/neuromuscularsystems ammonia,possiblyedem macanrange
frommildconfusiontocoma,aasterixis
Renalfailure(hepatorenalsynddrome)kidneyshaveo outputBUNandCreaatinine,hyperosmolarw/lo owNa+.Rapid
onsettoflowurineoutput.Pooorprognosisw/thisonset(22wksifrapidonset,6wkssifinsidiousonset)
Respiiratoryfailure(hepatopulm monarysyndrome)lungshavehypoxemia+intrapu ulmonaryvasculardilatatio onmostlydue
toventilationperfusionmismattch.
w/outUVlightsource),spider Jaund dice,hypoalbuminemia(asscites,edema),hypoglycem mia,portalHTN(ascites,sp plenomegaly,caputmedusa,
hemo orrhoids),coagulopathiesffromclottingfactorproduction
Fetorrhepaticusbodyodorthhatismusty/sweet/sourdu uetomercaptanformation nviabacterialactiononGImethionine
Hepatocytedeathstimulatesnodularregeneerationofsurviving
hepatocytes(macrronodulesseveralcmorm micronodules<3mm)
Reorganizationofentirevasculararchitectureofliver:collagen(typeII,
II)depositedinspaaceofDisse,formsconnecttingfibrousseptaethat
distortsthelobule..Centralveinportaltraacts,portalportaltract.
Bloodshuntedaro oundparenchymaunderrperfusion.Obliterationoff
portalareabiliarycchannelsjaundice.Sinu usoidalendothelialcell
fenestrationsarelo ostalso(SpaceofDissebecomesacapillarylike
channelnosolute eexchangesbetweencellssandplasma,secretion of
albumin,clottingfaactorscellfxlabssho owalbuminand
prothrombintime))
Cholestaasis
Impairedbilesecretionbycells(dysf sfx)orflowthroughbilechannels(obstruction).
Extrahepatic(usuallysurgicaalsolution):stonesinbileduct,tumorswithin/comp pressingbileduct
Intrrahepatic(usuallynotsurrgicalsolution):alcoholicliverdisease,primarybiliarrycirrhosis,viralhepatitis,meds
Results:
Liveercellinjury(alkalinephhosphataseandGGTP)
osis)
Bilirrubinaccumulationinseruum(totalbilirubin),jaun ndice,icterus
Pruritis(possiblyfrombileaciidsinskin)
nofNO)
Choolesteroldepositioninskinn,tendons(xanthomas)
Fatmalabsorption(LowabsorrptionofADEK)
Moorphology:Whetherobstruuctiveornonobstructive,bilepigmentaccumulatesinparenchyma.Dropletsin
heppatocytesappearfeatheryy.Bileplugsincanalicularspaces.Kupffercells,apo optoticcells
obstructive,bileductdistenntion+reactivechangeinportaltractsductularproliferation(reactioncellssregenerate
Ino
asd
ductcellsandhelptodetoxxsomeofthebreakdownproductsofbileinthespaces)edema,neutrophils
Cholicacid,chenodeoxycholicacidaactashighlyeffective
detergentstosolubizelipidsingutlum menandsolubilizingwaterr
insolublelip
pidsfromhepatocytesinto obile
1020%decconjugatedinintestineviabacteria,butfecallossis
matchedbyydenovosynthesis(0.5g/d day).
Fecallossofsterolsinbilesaltsandre
esidualfreecholesterolistthe
onlyeffectivvewayforeliminationofe excesscholesterolfromthee
body
95%reabso orbedinileum,returnedviaaportalbloodandreused.

Causesoflowbile
e
Hepatobiliarydisease(secretion),P
PrecipitatedbileacidsinLO
OW
pH,bacteriaalovergrowth(deconjugateacids),malabsorption(ileeal
disease)

Liver/BiliaryTract
BilirubinMetabolism:
Inmacrophagess(spleen):Heme(Hemeoxygenase)biliverdin(b biliverdinreductase)
bilirubin(UCB)
Blood:lipidsoluuble,hydrophobicUCBtravvelsinbloodattachedinalbumin.Cannotbe
excretedinurinee
HepatocytestakkeupUCB,conjugateUCB+glucuronideviaUDPGTinSERCB(water
soluble)
Canaliculi:CBisexcretedintocanaliculiviaaorganicaniontransporte er(MRP2)inbilevia
biliarytractinto
ogut
Gut:IntestinalbbacteriadeconjugateCB colorlessurobilinogen urobilin(orange),
o MostUBp passedinfeces.
o ~20%reaabsorbed,90%ofthisremo ovedbyliverandreexcretedinbile,remainder
passedinurine
Normally,>80%serumbilirubinisunconju ugated
o HighUCBtotalbilirubinrarely>5m mg/dL(normalliverfx),neonataljaundice
commoneestcauseofelevatedUCB
o GilbertsDDisease(AD?)ismostcommonadulttypeofUCB(~5 5%),mostlyreduced
UDPGTacctivity.M>F,onsetinteenss,w/stressorfas ng,be enigncourse
o CriglerNaajjarTypeI(AR):geneticlaackofUGT1A1,Fatalwitho outtransplant
o CriglerNaajjarTypeII(AD):Nonfatal,reducedactivityofUGT1 1A1reallyyellowskin
butPheno obarbitaltxcanimprovebiilirubinglucuronidation(hyypertrophies
hepatocellularER)
o DubinJoh hnson(AR):hereditarydeffectinMRP2canalicularprroteinthattransports
bilirubingglucuronides,relatedorgan nicanionsintobile.Darklyypigmentedliver.
o Rotor(AR R):asxhyperCB,livernotpigmented.Jaundicew/nosx.
Hepaticjaund dice:hepatocellular,intrahepatic Neonatal:hepaticbiliru
ubinglucuronyl
Normal(nojaundice): Prehepaticjauundice:overproductionof Posthhepatic:obstructive(extrahepatic)cholestasis.
cholestasis.(C
Causesviralhepatitis,alccoholichepatitis transferaselowatbirth.Normalrbc
Blood:CB<20%,liverenzymes bilirubinand/o
orliveruptake.(Causess Bileduuctisblockedsobilirubinccantgotointestine
Jaundice anythingthaatcausesdamageofcellstthemselves). breakdownoffetalrbcss(w/HbF).
normal(AST,ALT,ALP,GGT) Extravascularhemolyticanemiaothercauses (causeesdruginducedslowedfflow,biliarycirrhosis,
Cellsdamaged dandcantconjugatebiliru ubin. Accumulatebilirubinaffectsbasal
Stool:Normal(hasUBG G) w/outurine eUBGGilbert,CriglerNaajjar, DubinnJohnson,Rotors,Gallston ne,PancreaticCain
Blood:AST<ALT,ALP,GGT,CB B(2050%) ganglia,causeskernicte
erus(toxic
Urine:HasUBG,NOCB B(never Physiologicjau
undiceofnewborn) headoofpancreas).
ALCOHO OLIChepatitishasAST>ALTW/alcohol, encephalopathy).Biliru
ubinbecomes
anormalfindinginurin
ne Blood:
UB,AST,CB<20% Blood:HIGHCB(>50%), AS,ALT,ALP,GGT
yougetttoASTed morepolarw/UVlightbecomes
becausedoesnthaveccontact Stool:D
Dark(UBG) Stool:SUPERPALE(CBcantgetthere),claylike
Stool:~
~NormalUGB,pale/claylikkestool watersolubleandcanbbeexcreted
w/bloodinitsmetabolism) Urine:
UBG,noCB Urine:Dark(CB)
Urine:DDark(UB,CB) withoutconjugation.
Blo
oodborneinfections:syste emicorarisinginabdomen nTB,malaria,amebiasis,staphylococcal,salmonello oses,Candida
Viralsystemicinfection:EBV,CMV(neonates,lowimm munity),Yellowfever,Herpe esvirus,adenovirus,rubella,enteroviruses Fulminanntacutehepatitis:rareH HBV>HAV>HCV.Massiveto osubmassivenecrosis,rappidonsetof
Viralhepatotropicinfection: HAV(food,waterfecalo oral),HBV(parenteral,secretions,perinatal),HCV(paarenteral,secretions),HDV V(only failure(w within2wksofonset).Fulminantusuallycausedbyydrugs,toxins.
w/HHBV),HEV(waterfecalo oral) Chronichhepatitis:mostHCV>fewH HBV,HDVw/HBV.Mayormaynotprogresstocirrho osis.Chronic
Clin
nicopathologicsyndromessafterhepatitisexposure: usuallycaausedbyalcohol,virus(no otHAV),NAFLD,toxins,biliiarydisease,HH,Wilsons,A A1AT
Acuteinfectionw/reco overy(happensw/allhepatotropicviruses)asx(serrologicevidenceonly)orsxx o Loobuleshaveapoptosis,steatosis.Macrophageaggrregates.
Infections o Hepaticfailure(eencephalopathy)2wksfro omsxonset.Nostigmatao ofchronicdiseaseviralheepatitisonlycause12%ofcases. o PoortaltracthasMAINDAMA AGE(lymphocytes,plasmaacells).
Viral(Seebug Drug/chemicalto oxicitycause52%(acetaminophencauses50%).Auttoimmune(15%),miscellan neous(mycotoxins,ischem mia, o Chhronicactivehepatitsinfllammationatinterfacezonesarebridgedbyne ecrosis.
chartformore massivemetastaases,venousobstruction,fattyliverofpregnancy). Irrreversibledamage(fibrosiss)1stportal,thenperiporrtalzonesarebridgedbyfibrosis.
info) o Necrosisentire eliverorrandomareas.Grrossliverappearsreducedsize,limp/red,wrinkledcaapsule.Cutsurfaceisduskky,red, Carriersttate:HCV>HBV
mushy.Microscopically,losecelldetail.Parenchymalcollapse.Prreservedportalareas.Inptswhodienoinflammattion. HIVinfecction:HCV>HBV
Survivalmassivvephagocytosis;postnecrroticcirrhosis:scars+regenneratedlivercellnodules. HBV:DN Avirushasgroundglasscytoplasmandsandednuclei
o LobuleshaveMA AINDAMAGEdamaged/in ndisarray.Theyareinjured(ballooned,apoptosis,se everenecrosis/collapse, HCV:Steeatosis(focalinlobules),lymphocyteaggregates
Kupffercelllipofuscinpigment);responsetoinfection(macrophageaggregates,lymphocytes,plasmacells),Dysfx(choleestasis, Acutevs ury,inflammation,dysfxinacute.In
sChronicActiveHepatitisLobulesindisarrayinju
steatosis). chronicaactiveseeportalperiporttalareainterfaceinflammaation/necrosis.
o Portaltracthasssomeinflammation(lymph hocytes,plasmacells,choolestasisductularrxn)
Auttoimmunehepatitis:abno ormalTcellregulation(CD44,CD8cellsmediateinjury).Geneticpredisposition, See gammaglobulinswithNO Oserumevidenceofviralh hepa s.
envvironmentaltrigger(viralin
nfection,drugs,herbs). Typessdeterminedbyspecificseerumautoabs.Usuallyno oantimitochondrial(PBC).
Autoimmune herautoimmunediseases((celiacdisease,UC,RA,SLEE,SS.
Occursinsettingofoth US type1ismorecommon(aage10elderly).InEuropeType2ismorecommon(p pediatric)
Respondstosteroids,immunosuppression. Morp phology:Classichistologyanystageofchronichepatitis+plasmacellclusterssatinterfacearea,()bileductinjury.
F>M(8:2),W>B,riskkinNorthernEuropeans. Manyymanifestacutely,amyprresentw/fulminantcourse.Ifsevere~40%diein6m mow/outtx,cirrhosis/livertransplant.

Liver/BiliaryTract
AlcoholicLiverDisea ase Nonalccoholicfattyliverdisease::Steatosisw/minorinflammation;steatohepatitis(NASH).Histo
Endstagecirrhosis.
Pathogenesis:activecelldamagehepaatocellular andchaangessimilartoalcoholicliiverdisease
Irreversible(?)changes.
damage(ballo ooningandnecrosis);Mallo orybodies NNASH(nonalcoholicsteato ohepatitis)adxofexclusiionhighserumaminotransferases,

Bridgingfibrosis(central
(cytokeratinb bundlesincytoplasm),Neutrophils GGGTP.Alcoholintake<20gg/day,labtestsnegativefo orHBV/HCV,negativeFestudies,
portalzones,thenportal
arounddamaggedhepatocytes,earlydelicatefibrosis nnegativeautoimmunesero ology.M=Friskfactorsarreobesity/metabolicsyndrrome.
Drug/Toxin portalzones).
aroundcentraalvein(chickenwirefibrosiss),Steatosis CComponentshyperinsulin nemia,obesity,dyslipidem mia,hyperlipidemia,HTN,type2DM.
Induced Regenerativenodules
aroundcentraalveininitially(alwayspressentinNASH). MMostcommoncauseofchrronicliverdiseaseinUS.~~30%ofAmericansaffected d(70%of
Disease: (micromix+
exposureto Macrovesiculaarlipidincells(centrilobulaar). oobeseindividuals)
macronodules;ETOHif
toxin/therapeut 2hithypothesis:fataccumulation+oxid dativestress. CCanstopprogressionofsteeatosis,butNOTreversibleeinNASH.
ischemicnecrosisbroad d
icagentshould o Inmoststeatosiscases,ptsareasx.Dxisoften CCanprogresstoAdvancedffibrosis(3040%ofpts),cirrrhosis(1020%ofpts),hepatocellular
alwaysbe
scars(Laennecscirrhosis)),
incidenttal,duetofindinglivereenzymes. ccarcinoma(?Biggerinthepastbecauseliverdiseasewasdiscoveredlater)
includedinDdx Endstage(shrunken,
ALTASTT~1.52Xnormal;ALT>AS((reverseof 4findinngsnonspecificfindingsth hattogethershowNASH/A Alcoholicliverdisease:
ofliverdisease brown),Vascular
ETOHhepatitis).AdvancedNASH//cirrhosis HHepatocytedamage(swelling/necrosis)
Grossssoft,greasy,yellowliver..Wtis40006000gm. reorganization(endstage
w/norm malliverenzymescanoccur.Causeof MMallorybodies(cytokeratinfilamentsindamagedceells)
Alcoholicscanreverseitwithaabstinence.Continued nonspecifichistology.
mostcaasesofcryptogeniccirrho osis. NNeutrophilsatdamagedceells
ETOHHuseriskofinjuryand dfibrosisthatmay Mallorybodiesarerare
o Sympto omaticfatigue,malaise,oorvaguedull FFibrosis:perivenularearly((chickenwireatcentralveein)
leadtocirrhosis(1020%). now)
RUQab bdominaldiscomfort. ++Steatosistriglycerideaccumulation(microvesiculaarfat,initiallycentrilobularrthendiffuse).
Hem
mochromatosis WilsoonDisease A
A1antitrypsindeficiency
Labs:Ele evatedliverenzymes,hepaatomegaly, Patho ogenesis:Defectiveexcrettionofcopperinto AbnormallylowserumlevelsA1AT(AR).
Pathhogenesis: cirrhosis.Elevatedbilirubin,transaaminases.EKG bile.Copperaccumulatesinlivver>brain,eye,other A1ATproducedbyliiver,fxasproteaseinhibito orofelastase,
LostregulationofdietaryyFeabsorption.0.51.9gm m/yradded, QRS,TTwavefla ened/inverted..Assoc organns.Toxictissuedamageis duetocopper cathepsinG,proteinaase3releasedbyneutroph hilsatsitesof
presentsafter~20gmacccumulate.Sxatage4060 0yrs(sxlater w/hypotthyroidism(fromfibrosis,d developmentof catalyyzedROS.WNDgeneisATTP7B,encodesan inflammation.
inF).Fetoxictotissues(generatesROS)lipidpe eroxidation, antithyro oidabs).1/31/2havearth hropathy ATPaseenablingcoppertranspportacrossthe Deficiencylungtissuedestructionemphyssema.
stimulatesstellatecellsttocollagen.**Hemosiderin (resemblesosteoarthritis). canallicularmembrane.Mutatiooncapacityto Cirrhosisdevelopsthrroughaseparatemechanissm!Most
deposition,Cirrhosis,Pa ancreaticFibrosis** Causes:FamilialForm:ARinheritan nceofHFEgene incorrporatecopperintocerulopplasmin commonnormalgeno otypePiMM.Commonestsignificant
Feaccumulatesinmostlyyparenchymalorganslivver(+20gm, (C282Y,H H63D),onsetage4050,lo owhepcidin ceruloplasmin.Lessceruloplas minmeansless deficiencyvariantP
PiZZ.WithPiZZgenotype A1ATlevels
normal~0.5gm),pancre eas,skin(melanin+hem mosiderin), levels.HHepcidincirculatinghorm monesynthesized copperexcretedbile(theboodysmaincopper ~10%normal;riskfordisease.Heterozygote es(PiZM)have
>heart(brown,enlarged),>endocrineglands(fxx),>joints inliver,rregulatedbyironstores/inflammation eliminationmechanism).>300differentmutations, intermediateA1ATleevels.
(acutesynovitis,pseudoggout),Hypogonadism(testtes). actsonfferroportintoinhibitirontransport. notallcauseWND. Eppi:Mostcommonlydxped diatricgeneticliverdiseaseecansee
Hereditary(AR)geneticd defectofFeabsorption(HHtotal SeecondaryCauses:Thalassem mia, shhortlyafterbirth
bodyFecontentregulate edthroughabsorption,nottexcretion Sid deroblasticanemia,Chronicliverdisease Cause e:MostWND(AR):compooundheterozygotes Paathogenesis:100%ofPiZZZgenotypes(normalPiMprotein
hepcidinproteinpreventtsironreleasefromintestinalcellsto (H
HCV,HBV,Steatohepatitis,A Alcoholassoc 2m
mutatedalleles,eachw/diff fferentmutation. migratesfromERGolgiaapparatus)PiZvariantpolypeptideis
m
Metabolic plasmadeficiencycaussesFeoverloadotherpro oteins livverdisease),multipletransfusionsseen abbnormallyfolded.PolymerizesandaccumulatesinlivercellRER.
LiverDisease regulatehepidinlevels.Genemutationslackoffhepcidin moreinmales(becausewom menmenstruate) Sx:prresentsafterage5.Whennnonceruloplasmin Only1015%PiZZdevelopcclinicalliverdisease(?Othergeneticand
O
expressionHH.HFEggeneC282Ymostcommo oninadultsa Dx:highlevelsofserumiron,ferrittin;exclusionof bounndcopperspillsoverfromllivercirculation, ennvironmentalfactorshep patocyteinjurycausedby
channelthatisinsmallin ntcryptcellskeyinFeab
bsorption, secondarycausesofironoverload,,liverbiopsyif otherrorgansaredamaged.Braain,cornea,kidney, auutophagocyticresponse,m mitochondrialdysfx,activattionofNFkB
NorthernEuropeanCauccasians11%areheterozyygotes,only indicated d(showinghepatocytesstaainingdarkw/ jointss,bones,parathyroidglandds.Highurinary paathway).Hyalineglobulessincytoplasm(PAS+,diasta aseresistant).
20%penetranceinhomo ozygous,M:F6:1,Secondlesscommon Prussian blue).Importanttoscreen nfamily copperexcretion(screeningtesst).Brain Neonatalcholestasishepaatitiscirrhosis.Childhood d/adolescent
gene=H63Dhistidinetoaspartateatposition#6 63)AR;or memberrsforhighserumiron,ferriitin(?transferrin involvvementofbasalgangliapputamenhas heepatitiscirrhosis.Adultcirrhosisdefinitelyseen.
duetointake(mostlyfromparenteraltransfusio ons). saturatio on>60%M,50%F).Heterozygotesusually atropphy/cavitation,leadingtonneuropsychiatric Sxx:canvaryallthewayfrommhepatitis(cholestasis)tocirrhosis
Sx:U
Usuallyasxatdx.CausesBronzediabetesGlycossuria havelow wofreallyloworgandamagenormallife manifestations.KaiserFleischeerringsinmost (nneedlivertransplant).Emp physema(avoidsmoking recruits
(diab
betesviadepositioninBce ellstoinsulinproduc on nanddirectly expectan ncyiftx/dxprecirrhosis. casessgreen/browncopperdeepositsin neeutrophilstolung).Hepattocellularcancer(23%PiZZ Zadults+/
impaairedinsulinsensitivity),brronzeskinpigmentation(gray/brown Tx:usuallyregulartherapeuticphle ebotomy, Desceemetsmembraneincorneeallimbusbyslit ciirrhosis.
patchhes,canbeseeninmouthprobablysecondaryto chelation nw/deferoxaminenotusuallydone lampexam(supportsWNDdx).. Morphology:hyalineglobullesincytoplasm(PAS+,diastase
M
melaanin/irondepositionaroun ndsweatglands),cirrhosis.fatigue, Morp phology:livermorphology yisnotspecific. reesistant).Onlydistinctiveffeaturesteatosisisclueinneonates.
atypicalarthritis,hepatomegaly,arrhythmias,cardiomyo opathy, Steattosis,acute/chronichepatittis,macronodular
impootence,(infection).Deathcirrhosis,cardiacdisease e, cirrhoosis.Massivenecrosisisraare.Rhodanine
hepaatocellularcancer.200X riskofhepatocellularcarccinoma stain showshightissuecopper (nonspecific)
Dx:tiissuecopperlevel>250um m/gmdrywt. PAS+
Pathogenessis:Intrahepaticbileductd destruction(mediumsized).Chronic,progressiven nonsuppurativeportalinflaammation,scarring.Insidiiousonset, Tx:liverttransplantation.
nosxforyears.Leadstocirrhosis,live
erfailure,death.riskofhepatocellularcarcinoma.Autoimmunee ology?A AbantimitochondrialIgM M,others. Sx:F>M(6:1),2080yrs,peak40500yrs.Onsetpruritis,fatig gue,then
Prim
maryBiliary
Assocw/oth herautoimmunecondition ns.DonebySTELLATECELLLS xanthomaas,xanthelasma.Latejaun ndice(liverfailure),stigmattaofcirrhosis.
Cirrh
hosis
Morphologyy:portaltractsareinflame ed(floridductlesion)lym
mphocytes,plasmacells,+/eosinophils,Ductdestrucction+/granulomatousreeaction. Labs:antiimitochondrialabs(~95%)).Earlyserumalkalinep phosphatase,
Eventualinttrahepaticobstructiontofflowofbile.Upstreamb bilestasisleadstohepatocyyteinjurycirrhosis.Obseervegreen,micronodularssmallerliver. GGMTandcholesterol.Lateh hyperbilirubinemia.
Pathogenessis:Processaffectingbothintraandextrahepaticbile educts.Inflammationw/o obliterativesclerosisofsom mesegments.Dilationoffintervening Tx:liverttransplant
nonscleroticsegments.Classicbead dedpatterninradiograph hiccontraststudies.M>F((2:1),2040yrs.MaybeimmmunemediatedgutactiivatedT Sx:70%h havehxulcerativecolitis.A Asxpersistentalkalineephosphatase
Prim
mary
cellsorbactterialiver.crossreactw/bileductags.Absan ntismoothmm,antinucle ear,atypicalpANCA,rheum matoidfactor. levels.Sxxprogressivepruritis,fatiiguejaundice.Diseasecoourseismany
Intrahepatic Sclerrosing
Morphologyy:affectedductslympho ocyticinflammation=cholaangitis.Concentricperiducctalstromalfibrosis=sclerosis.Resultsinprogressivve years(5117).Lateseveredisease,sttigmataofcirrhosis,risk kof
BiliaryTract Cholangitis
stricture/obbstructiontobileflow.Bile
eductseventuallyatropyaanddisappearreplacedbysolidcordlikescar.Interveningnonscleroticducttsdilated, cholangio ocarcinoma.Duetochronicinflammation.Alsorisko ofchronic
Disease inflamedb bilestasisleadstohepatoccyteinjury.Endstageisno
onspecificbiliarycirrhosis.. pancreatitis,hepatocellularcarcinoma.
VonMyenb burgComplexes: CaroliDisease:Dilatedlargerducts
PolyycysticLiverDisease: CongenitalHepaaticFibrosis: ofintrahepaticbiliarytreeAR
Anom maliesof closeto/witthinportaltracts,
Multtiplecysticlesionslined portaltractshaveecollagenous
theBBiliary smallclustersofdilatedbile
bycuuboidalflattenedbiliary tissue,separatelliveroddly
Treee ductembed ddedin
epithhelium,containstraw persistentmalforrmed
(inclu
uding fibrous/hyalinizedstroma.
coloredfluid,F>MAD, embryonicbiliaryytreefibroses
livercysts) Fromresiduualembryonicbile
asso
ocw/ADPKD overtimeAR,aassocw/ARPKD
ductremnantsSporadic
Liver/BiliaryTract
Congenital Alaagillesyndrome Syndromicpaucityofbiled
S ductstheductsarentpre esent.DuetomutationofJagged1onChromosome20p
Centrilobularnecrosis(Lsi
C idedheartfailure,shock) hepaticarterycompromiise,portalveinobstruction n,intra/extrahepatic
Imp pairedbloodflowto
thrombosis.Centrilobularhypoperfusion/hypoxiaischemicnecrosis.Seeessophagealvarices,splenom megaly,INTESTINAL
liveer
congestion
c


Combination:Sinusoidocc
C lusion(sicklecellanemia,DDIC),systemiccirculatoryccompromise,cirrhosis.Seeeascites,esophageal
varices,hepatomegaly,elev
v vatedtransaminases.
centrilobularhemorrrhagicnecrosis==thisisth hegrossmottledliverwithNUTMEGappearance.Redtissueiscongested
Circulatory Imppairedbloodflow
(centrilobular),palettissueisviable(periportal)).Microscopically,seecongestednecroticcentrilobuularareas,viable
Disorders thro
oughliver
periportalareas.
PeliosisHepatis:sterroid,oralcontraceptiveusemayleadtosinusoidaldiilation.Usuallyasx,butmayhavepotentiallyfatal
intraabdominalhem morrhageorhepaticfailure e.Lesionsgoawayaftertxstopped.

Heppaticvenousoutflow Chronicpassivecongestion
C n(Rsidedheartfailure)centrilobularcongestion,h
hepatocyteatrophy.Hepaticveinthrombosisin
obsstruction BuddChiarisyndrome.See
B easciteshepatosplenomeggaly,abdominalpain,elevaatedtransaminases,jaundice

Preeeclampsia,Eclampsia AcuteFattyLiverofPPregnancy IntrahepaticCholestasisoffPregnancy
710%ofpregnanciesHTN,proteinuria,peripheraledema,coagulationabnormaalities,sometimes Womanin3rdtrimesteer
asppectsofDIC. Sxfromhepaticfailure re(bleeding,N/V,jaundice,,coma).2040% PPruritisonsetin3rdtrimestterfollowedby
Hepatic
Eccclampsiawhenassociated dw/hyperreflexiaandconvvulsions havepreeclampsiaw//this. ddarkeningurine,lightstoolls,jaundice
Disease
HELLLPsyndrome:hemolysis,elevatedliverenzymes,low wplatelets Dx:confirmmicrovesiicularsteatosisw/Sudanblackstain.Difficultto G Generallybenign,butmom matriskfor
w/Pregnancy
Liveer:periportalsinusoidscon ntainfibrinw/hemorrhageintospaceofDisse(getpe eriportal distinguishfromhepaatitis. ggallstones,malabsorption,someof
heppatocellularcoagulativene ecrosis).Cangethepatiche ematomaanddissectiono ofbloodunder ffetaldistress,stillbirths,prematurity
Glisssonscapsule(mayrupturre) Tx:terminatethepreegnancy
Livercelladenoma(beenign): MetastaticNeooplasms
Mostinyoungfeemales,assocw/longterm museoforalcontraceptive es.Alsomen,assocw/anabolicsteroids. morecom mmonthanprimarytumo ors
Glycogenstoraggedisease Multiple breast,lung,colon,panccreasaremostcommon
Mostsolitary(80%).Oftenbeneathlivercapsule.530cmddiameter,welldemarcatedd.Tan, origin
yellow/greenfro ombile. Anycanccer,especiallyfromorganssdrainedthroughportalveein
Microscopic:pro oliferatinghepaticytesinsheetsandcords,oftenlooklikenormalcells.NObile eductsorportal toliver
triads.Largeblooodvessels. Classic multiplesmallernodulesiinenlargedliver.Often
Dangerssubcaapsularrupture,bleeding,e especiallyinpregnancy.Rarelycontainortransformto clinically silent.Ifsingleorfew,no
odulesmightberesectable.
hepatocellularccarcinoma.OftenmisdxasHCC.
Malignant Hepaatocellularcarcinoma/HCC C(HBV/HCV,ETOH,HH) Hepatocellularlamellarvariant(no Hepatoblastoma(pediiatric) Angioosarcoma Cholangiosarcoma
Neoplasms Mostcommonprimarylivercancerworldwide.M M>F(2:1). cirrhosis) Mostcommoncchildhoodliver (thorootrastassociatedw/ (PSC,chronicinflammmation/infection)
MostcasesgloballyarerrelatedtochronicHBVinfe ection. Fibrolaamellarvariant:5%ofall tumor(~80%,bu utrare).Most riskoffangiosarcoma,HCC, Malignancyofbileductepithelium(adenocarcinoma).
Otherfactorschronicaalcoholism,nonalcoholicffattyliver HCC.22040yo,M=F.NO casesininfants~~1yr.riskif cholanngiocarcinoma;PVC, 90%ariseinexxtrahepaticbileducts.UShas
disease,chronicHCVinfe ectionw/cirrhosis,aflatoxiin.Also settinggofchronicliverdisease prematurew/low wwt.M>F arsen ic) incidenceofinttrahepatictumors.Donootarisein
hereditaryhemochromaatosis,A1ATdeficiency,glycogen (noHBBV,cirrhosis)prognosis (2:1),W>B(5:1).. Rare,3rdmostcommon cirrhosis.
storagedisease,hereditaarytyrosinemia.Cirrhosisalso better..Large,hardtumor malformationss,nocirrhosis. primarylivertumor. Riskfactors(mostcasesarewithout):clonorchis
playsavariablerole.Chronichepatitiscyclesoff transecctedbythickfibrous Solitary,solid/taantumor.Well Riskw/exposureto sinensisinfection,thorotrastexposure,congenital
death/regenerationaaccumulationofDNAmutations. bands (collagenlamellae). circumscribed,b bulging.Asx PVC,arsenic,thorotrast. intrahepaticduuctdilation,HCVinfection
Classiconelargetumo orw/manysatellitetumors(or Welldifferentiated abdominalmasss. Lowgradeproliferationn MixofCCA+HCCpossibleduetooriginffromcommon
multiple/diffuse)allcauseanenlargedliver.Palee,green hepato ocytes.Eosinophilic, Smallroundimm mature ofmalignantatypical, precursorcell.
frombile.Invadehepatiicbloodvessels(especiallyyveins). abundaantcytoplasm hepatocytesinccords plumpendothelialcells Invadingductscausedesmoplasticstromalresponse,
Proliferatinghepatocytes.Welldifferentiated (mitoch hondria),prominent 2patternspurreepithelialcells thatformvascular hard/grittywhitetumors
anaplastic(doesntlooklikeliver). nucleoli ormixedepithelial+ spaces.
Clinicalfeatures:sxrelattedtochronichepatitis,cirrrhosis. mesenchymaltisssues(cartilage, Highgrade
Vagueupperabdominalpain,malaise,fatigue,wt. bone,striatedmmm),teratoma cellularity,solid,
Senseoffullness,mass.Liverenlarged,palpable like.Genetics mutationsin abnormalmitoses,
nodularity,distinctfromcirrhosis.Jaundice,fever,, WntBcateninssignaling spindled.Endothelial
esophagealorGIbleedin ng. pathway. originhas+stainsfor
LabsserumAFP(10 00Xnormal)butCEAnot .(AFPis Arisefromapluripotentstem Factor8,CD31.
alsoingermcelltumo ors,rarelyw/cirrhosis,hepaatitis, cell,mimicsnorm malfetalliver
posttraumaticregenera ation) development.
ReallyhighAFPlevels.
Mayhavefocalh hematopoiesis
likenormalfetallliver.
Completeresecttion+chemotx
==80%5yrsurvvival.

TheBiliaryTraact

1Lsecretedperday;Hasacapacityof50mL.Gallbladdernot
reequiredforbiliaryfx.

H
Hasnomuscularismucosaeeorsubmucosaonlyhasamucosa
lin
ningw/asinglelayerofcolumnarcells,afibromuscularlayer,a
Normal laayerofsubserosalfatw/arteries,veins,lymphatics,n
nn,and
paraganglia,andperitonealcoveringexceptwheregallbladder
embeddedintheliver

Congenital Majoranomaliesareraare
Anomalies Gallbladderabsent,d
duplication,bilobed,folded dfundus(Phrygiancap),ab
berrantlocations(510%)
Above:a Bileducts:mayhaveaggenesisofallorpart(withotheranomaliesinspleen//heart/GItracttheonesidedstructures),atresiaa(fetalperinatal) P
Phrygiancapfrominfolded
dfundus

Chholesterolstones Pigment(bilirubin
n)stones
predominantforminno
onwestern
(80%ofthosefoundinwesst,industrializedcountries) countries

Mo orphology: Mucushypersecretio on(scaffoldingandcementtallowssustained indevelopingcountries,Asia.unconjugated dbilirubinin
Contain50100%chole esterol(100%cholesterolaarerare).Radiolucent,yellow.Mosthave crystaltrapping,aggrregation,growth) bile.MixtureofabnormalinsolublecalciumsaltssofUB
mixedcomponents.Caanberadioopaque(1020 0%)addgray,white,blackkcolors. Clinicalfeatures:
C w/inorganiccalciumsaalts.Infectionofbiliarytractcauses
Singleormultiple.Mmm(gravel)tocm.Rounded,,barrelshaped,orfaceted d(formedintight 75%areasxforyrs/d decades.14%peryrdeve lopsx(riskw/ me). releaseofmicrobialBgglucuronidaseswhichhydrrolyzebilirubin
apposition) Mainsxbiliarypainn.Thisissevere,usuallyinRUQ.Constantor glucuronidesandun nconjugatedbilirubiningallbladder
Cholelithiasis
Risskfactors:4simultaneousdefects: intermittent(colickyy)relatedtoobstructionoofbileexcretion.Also Blackgallstones:forminsterilebile,gallbladderindicate
Supersaturatedbile( cholesterolsecretionbyliver)Conditionsthatchangebile relatedtogallbladderinflammation(cholecystiitis). chronicintravascularrhemolysistoomuchtheerefor
compositionchole esterolconcentration(agge,female,femalesexhorrmoneslike Complications chasbypass
ut,severeilealdiseasesuc
conjugationandprecipou
estrogen/progesterone e,contraceptives,pregnancy,weightobesity,rapidwtloss;D19Hgene o Obstructionb bileducts(obstructivechoolestasis),pancreatic surgery).Radioopaque,many<1.5cm,crumble,speculated,
variantproteininvolvvedincholesterolsecretion nhyperlipidemiasyndrommes),bilesalts ducts(pancreaatitis).Smallstones/graveelhaverisk.Large molded.
(inbornerrorsofbileacidmetabolism) stoneshave riskbuterodeintoandobbstructthesmallbowel Browngallstones:form mininfectedducts(bacteriaor
Gallbladderstasis(freeecholesteroltoxictowall;nucleationintocrystals))riskw/acquired (gallstoneileu
us) parasites)theyarerad diolucentmadeofcalciu umsoaps
hormonal,nervedisord ders(spinalcordinjury),starvation(prolongedtotalp
parenteralnutrition) o Empyema,perrforation,fistulae,inflamm mationofbiliarytree (glucuronidaseunconjugatesbilirubinandformssthis).Soft,
Acceleratednucleation n(proantinucleatingprroteins,calciumsaltmicrop precipitates) o riskofgallbladdercarcinoma soapy,greasy
Acu uteCalculousCholecystitiss(inthepresenceofstone es):
AcuteAcalculousChole ecystitis: ChronicCholeccystitis:
Chemicalirrita ation(NOTbacterialinfeection)inflammation Ischemia/poorperfusion(NOTcausedby Likelyarresultofgallstones+lowleevelacuteinflammation.LLongterm,somereportantecedent
resultingfromobstrucctedgallbladder90%necckorcysticduct gallstones)cystticarteryisanendarteryithas attacks. Sxsimilarasacutecholecyystitis.Gallstonesrolenootclear(butpresentin90%%ofcases).
obstruction.Bilelecith
hinsarehydrolyzedbymuccosalenzymes.Atoxic nocollaterals.
riskofgangreneand Sameriskkfactors.Obstructionisntnecessary.Similarsx/mo orphologycalculi.
Cholecystitis
form(detergent)candisruptmucuslayertissu ueexposedtoirritating perforation.Tendtohappeninseverelyill 1/3ofcaaseshavemicroorganisms(E.coli,enterococci)
Acuteorchronic,
acutecanbe bilesaltscanbecomeinflamed. hospitalizedpt(++additionalriskfactorsseevere Morphollogy:Lymphocytes,plasmaacells,macrophagesfrommucosatoserosa.Inseve erecases,
superimposedon Muraltissueswelling PGreleaseinflammattiondysmotility trauma,burns,se epsis/infection,hypotensio on
fibrotic/tthickwalls.Rokitansk kyAshoffsinuses benignreactiveproliferatiion.
chronic.Nearly furthertissueswellingmucosalbloodflow(riskofnecrosis, w/multisystemo organfailure,DM,
Epitheliuumpouchesdown,insinuattesthroughwall.Mimicsaadenocarcinoma.
alwaysoccur perforation) hyperalimentatio on).
w/gallstones. Grossmoorphology:mucosanotulccerated,tanwhite.Lumen nclear,mucoid,greenbile;;stones
Clinicalfeatures:progrressiveRUQorepigastricpain.Mildlyfebrile, Insidiousonseto fsx(obscuredbyserious
InUS,oneofthe usuallyppresent.Wallthick,opaqque,graywhite.Serosa:sm mooth/adhesions.
anorexia,tachycardia,sweating,nausea/vomitinggabdominal precipitatingcon dition,oftensxnotgallbla dder
mostcommon porcela in(calcified)gallbladderriskofassociatedcarccinoma
indicationsfor tenderness.MildlyW WBCs,mildlyserumalkalinephosphatase related,dxneedssindexofsuspiciontoavoid
Hydropspsofgallbladderclearfluidfillslumen(longtermccompleteobstruction)
abdominal (obstruction).Hxofprreviousepisodeislikely.
bilirubinandjaundice mortality!)
features:similartoacutecholecystitisbutrecurrent,indolent.Fattyfoodintolerance.
Clinicalfe
surgery. ONLYw/commonbiled ductobstruction.Bacteriaalcontaminationand Morphology:Acu uteinflammatoryrxn
Epidemiologic
Complicaations:bacterialsuperinfection,perforationabsceess,ruptureperitonitis,
infectionmaydeveloplater.Maybeasurgicalem mergency(orptmay (neutrophils,vasccularcongestion,edema
distribution cholecysttentericfistula,aggravatioonofpreexistingillness
havemildsxthatresolvvebutrecur) grosslyenlarged,tenselumenhasbloodyybile
closelyparallels
pus,stones;mucosaishyperemic/red,wall
thatofgallstones
thick/edematouss,serosahaspus/fibrinexu udates)
IndifferentialDxxofacalculousvscalculous,
therearenospeccificdifferences


Cho oledocholithiasis:stonesinthebiliaryducts(generallyCBD) AcuteCholangitis:Bactterialinfectionofbileductss
Westcholesterolston nesformingallbladder(ste erile),traveltoducts Duetoobstructio ontobileflow.Stone(cho oledocholithiasis)ismostcoommoncause.BacteriaasscendthroughsphincteroffOddi.Tendtobecausedbyenteric
Disordersof Asiahighincidenceo ofbrownstoneformationin nducts(infected) gramnegaerobe es(Ecoli,Klebsiella,Clostriddium+bacteroides,Enteroobacter,Interococcus).Otthercausescatheters,paancreatitis,otherinfectionss.Ascending
Extrahepatic Ptsareasxorhavesxddueto: cholangitis:infecctionintrahepaticducts.
Ducts o Obstruction(bileecholestasis,pancreatitis) Sx:Feverandchills,abdominalpain,jaundice(classicsxtriad).
o Infection(acutecholangitis,liverabscesso orcirrhosis) Morphology:Muralneutrophilsmovetowaardinfectioninductlumenn.
o Concurrentacutecalculouscholecystitis Suppurativeacuttecholangitismostsevereform.Purulentbilefills//distendsducts.Sepsisism mainclinicalfeature.
TheBiliaryTraact
Com mplete/partialobstruction nofextrahepaticbiliarytreeelumenby3monthsof o Effectsofintrahepaticcholestasissinliverbiopsy(2/3casess)Parenchyma
agee (cholesttasis),bileductules(prolifferation/regeneration),Poortalareas
Perinatalform:80%.(mostcommon)bornw/n normalbiliarytree, (edema a/fibrosis).
destroyedafterbirth.Theoryamultihitprocessisresponsibleforinjury.. o Paucityyofbileducts(1/3cases)
Geneticpredisposition,autoimmunity.Viralinfectionofbiliaryepithelium Clinicalfeatures:Neeonatalform:slightF>M,A Asian/African>CaucasianinnUS.Normalwt/stools
BiliaryAtresia (reovirus,rotavirus,CMMV)
Fetalform:20%.Abno ormalintrauterinedevelop pmentoflaterality.Other initiallyacholic.Bilirubin~612mg/dL(no ormally<1.0mg/dLby1moonth).Moderately
anomaliesofonesided dorgansassociated. aminotransferases(cellinjury)andalkalinephosphatase(obstruc on)).Cirrhosisbyage36
Morphology:inflamma ation+fibrosisofextrahepaticductsleadsto month(secondarybiliarycirrhosis),deathbyaage2yrs.Txlivertranspllantationforcure
stricture.Onceductsh havenarrowedlumen,the engetintrahepatic (surgicalresecetion//bypassifptproximalbiled ductbranchesBUTbacteriialcontaminationand
cholestasisperiducttuleinflammationseco ondarybiliarycirrhosis. diseaseprogressionafter)
Choledochal Choledochalcyst:conggenitaldilationofthecomm monbileduct.Mostptspresentbeforeage10,F>M M(34:1).Ptshavejaundicee,recurrentbiliarycolilikeeabdominalpain.RUQmaass.Complicationsstoneeformation,stenosis,strictture,
Cysts pancreatitis,secondaryybiliarycirrhosis,riskoffbileductcarcinoma(inolderpts)
Tumors:
Ade enomas:similartoelsewhe ereinGItract
InflaammatoryPolyps:inflamed dmucosalprojections
Ade enomyosisofgallbladderbenignintramuralglandsw w/stromainahyperplasticcmuscularis.Canmimic
carccinoma.
o Gallbladdercarcinoma
Carrcinomaof Uncommon,F>M,older.
Gallbladder Pathogenesisirritation,traumachron nicinflammation.
Stones/west,infection/Asia
Sitesfundus/n
neck.
Adenocarcinom ma(invasive)mostinfiltrateintoliver,exophyticmasses.
Tumors Insidiousgrowth(incidentaldx,almostne everpreop,atdxmosthavveinvadedliverviabile
ducts,lymphnoodes)
Asx,RUQpain,aanorexia,N/V,wtloss.50%havejaundice.
Unccommon,M>F,older
Irrittation,traumachronicin nflammation.
Due etostones,parasiteinfectiion.
Carrcinomaof
Primmarysclerosingcholangitis.
Exttrahepatic
Ulce erativecolitis,choledochalcyst
BileeDucts
Ade enocarcinoma(invasive)m mostinfiltrate,ductalsmmall,obstructing/firmgraynodulesofwall;fibrousStrromalrxntoinvasion.Pappillary.
KlattskintumoratjunctionoffR/Lhepaticducts,slowgrowing,rarelymetastasize e(thisparticularvarianthasabetterprognosis)
Sxpainlessjaundice.HIGHserumalkphos,higham minotransferases,HIGHdire ectbilirubin,hepatomegalyy(50%),palpablegallbladdder(25%)
Needlethrustfromperrcutaneousliverbiopsy/traanshepaticcholangiograph hy
Iatrogenic Bileleakageintoperito oneumcancausebileperitonitis(inflammationinperritealcavity)
Injuryto Chemotxagentsinfuse edintohepaticarterycanccausedruginjuryofbiliarytree
BiliaryTree Biliarystrictureafteroperativetrauma(seenw/laaparoscopiccholecystectomy)10%associatedw/pancreatitis,externaltraum ma
Stricturesofcommonb bileductproximaltocysticcduct=usuallymalignant.

Pancreas
Emb bryology:madefromfusionoffdorsalandventraloutpouchin ngsof
Assecretoryrrateschange,the CyssticFibrosis:CFTRis Pancreaticsecretion:
foreegut(wk7)
electrolyteco
ompositionof deffective,preventsClrecycling Cephalicphase:sighht/smell/eatingAcinarcell
Seccretin:stimulatesreceptorsthatactivateadenylatecyclasean ndinitiate
pancreaticsecretionchanges:Low ductsecretionresultingin stimulatedtoreleassesecretionsbyAch,VIP(Ach
bicaarbsecretioninductcells,ScellsinduodenumstimulatedbyH+(max
flowrate(Na++/Clpredominate, thiccksecretionandplugging. potentiatesactionoofsecretin.)
secretionatpH3),luminalFA
LowK/HCO3);highflowrate Itsthemostcommonlethal Gastricphase:stom machdistension,amino
CCKK:promotesdischargeofdigesttiveproenzymesbyacinarcellss,stimulated
(bicarb,Na+p
predominate,low genneticdisorderofCaucasians. acids/peptidesinguutlumenstimulate
byFFA,peptides,AAs
Cl/K+) Inabilitytorecyclechloride mechanoreceptors causevagovagalreflexefferrent
Proenzyesreleased:(activatedbybrushborderenteropeptidase ein
reqquiredforbicarbsecretion. vagalfiberscauseggastrinreleasefromGcells(whichact
duoodenumlumen,activatedtrypssindoesthistoo)Trypsinogen n,
CFptshavesecretionof asendocrineonpanncreaticacinarcellsecretion)
Chyymotrypsinogen,Procarboxype eptidase,Proelastase,Allikreino
ogen,
panncreaticenzymesand Intestinalphase:thhemostimportantphaseinitiiated
ProphospholipaseA/B.Thereisatrypsininhibitorinthezymoge engranule
panncreaticinsufficiency byentryofgastriccchimeintointestinallumen
soeenzymesarentactivatedinthe ere.
(me echanismunknown).Causes chemoreceptorsduuodenum(Scells)detectacid,rrelease
AdvvantagesofmaintainingintraluminalpHatnearlyneutralvalu ues
Normal maldigestion,malabsorptionof secretin(stimulatessbicarbsecretionbyductcells..I
Preventsacidpepsindamaagetoduodenalmucosa
nuttrients(onlyoccurswhen cellsdetectfat,releeaseCCK(actonacinarcellsecretion
ProvidesfunctionalpHforpancreaticandbrushbordere enzymes
90%%ofpancreasfxislost). ofenzymes).CCKthhoughttoactivatevagovagalrreflex
solubilityofbileacidsan
ndFA
SeccretionsofthePancreasandth heirfxs
Accinarcells:secrete
diggestiveenzymes. Enzym mes:secretedinzymogenform mandstored
StiimulatedbyCCK, inzym
mogengranules.
Se
ecretionrate0.2 Bicarrb:secetedbyductcellsviaCl/HCO3
0.3
3mL/min exchaanger(apical)drivedependsonduct
luminnalCllevels;luminalmembran neCFTRCl
channeliskey(regulatedbycAMPd dependent
kinasse).

Ageenesis Conge
enitalCysts Annular Ectopic Pancreaticdivisum
m
Congenital
(usuallyinsmallintestine/stomachwall)~11cm
Anomalies Usuuallyassociated Ventralprimordiumfuses Failedfusionofdu
uctsystemsdorsal
anomaalousducts.Canbeinpancreaasalone(sporadic)orcoexist nd nodule,inpylorusitmayleadtoinflammationn,
inadvertentduct w/wwidespreadsevere w/head.Formsringin2 2 partof +ventralprimordial.Smallductof
w/kidn
ney/livercysts(ADPolycysticKidneyDisease,VHLdisease edema,obstrucction.Apotentialsiteofisletccell
traumaduring mallformations duodenumresultsind duodenal Santorinidrainsmostofpancreas.
w/brain/renal/retinalvascularneoplasms) neoplasms.
surgery/endoscop inco
ompatiblew/life obstruction Canleadtochronicpancreatitis
Microsscopiccystslarge(5cm).Th
hinfibrouscapsule.Singlecell
ycanleadto
epithe
eliallining,mucoid/serousfluid. CanleadtoanttisusscesptioninMeckels
pancreatitis IPF11iscritical Sx:gastricdistention,vo
omiting 310%haveit
diverticulum.

Chronicpanccreatitis:Parenchymaldestructtion,inflammation,fibrosispermanent.
Acutepancreatitis:Reverssiblediffuseinflammatorycond
dition.Pancreaticsubstanceisdestroyed.Activation+releasseofproteolyticpancreaticenzzymes.
Irreversible F).
inglandfx.Fibrogeniccytokkinespredominate(TGFB,PDGF
Causes:IntheWest80%o ofcasesassocw/alcoholism(M
M>F),(65%UScases),biliary Sx:abdominalpain(mildtosevere),constant/intense
tractdisease(F>M,gallsto
onesin3560%).Tissuechange
eswilldetermineclinical Pathogenesis:pancreaticaautodigestionbyinappropriateelyactivated Cause:multipleattacksofacute painprecipitatedbydemandsuchas
Sx:p
toupperback.Alsoanoorexia,N/V.HIGHserum
featuresmildedema/intterstitialinflammationtoseverrehemorrhage/parenchymal proenzymesproducedbyaacinarcells.Triggeringeventtrypsinogen pancreatitis((?),longterm ETOH/eating;sphincterofOdditone
amylase24hrs,thenlipase
ein7296hrs.Glycosuriain
necrosis. trypsin.Trypsinactivattesproenzymes(prophospholippases damage(alco oholabuse,duct opiaates/otherdrugs);canbesilent(firstsignis
10%ofcases(endocrinetissuedestruction).
membranes,proelastasebloodvessels,prekallikrein clotting: obstructiontrauma,calculi, insuffficiencyexocrineproblemsleadingto
Hypocalcemia,calciumsoaapsprecipitateinnecroticfat.
damage),lipase,amylaseaaresecretedinactivatedform (levelsare divisum,tum
mor,CF;hereditary malaabsorption,endocrineproblem msleadingto
Toxicenzymes,cytokines,inflammatorymediators
circulationsystemicinfllammatoryresponseshock pancreatitisPRSS1,SPINK1) maldigestion
DM));recurrentjaundice,stones,m
(vascularcollapse)
Morphology:hard,dilatedducts
+intraductalcalcifications.
Parenchymalfibrosis,lostacini
(number/ssize)
elevatedinserum)

Dx:rrequiresahighdegreeofsuspicion.During
attacckshaveserumamylase.Gallstone
nephosphatase.
obsttructioncanleadtohighalkalin
Morphology:mildinterstittialform(BVleakage CT/UUSshowspancreaticcalcificatio on
edema,lipasesperipancreaticfatnecrosis (PATTHOGNOMONIC).Malabsorption(wtloss,
white/yellow,chalky);seve
erenecrotizingform
hypooalbuminemicedema).
(Proteasesparenchymaalnecrosis,BVdestruction
Rx:pancreaticrest(foodd,fluidrestriction,supportivettx).Mostpts
hemorrhage).Acuteinflammmatoryresponsetotissue s
st Proggnosis:50%mortalityover202 25yrs;pancreatic
recoverfully,~5%diein1 wk(shock).Sequelae~50% %get
Inherited(trypsinautoinactivation(PRSS1cationictrrypsinogengenegermline destructionaddstodamagge!Cansometimeshave 10%develop
insuffficiency,severechronicpain,1
bacterialsuperinfection(G
GIGorgs),pseudocystweeksslater,sterile
mutationincleavagesite,AD,childhoodonset;SPINK1 serineproteaseinhibitor somecalcification/soponifficationbutitsmoreofan pseuudocyst
abscess)
Kazaltype1inactivation
nmutation,AR) accumulationthanhardcaalcifications.
Pseeudocysts(Nonneoplastic=ussuallyunilocular) Serouscystadenoma MucinousCystadenoma Solidpseudopap pillarytumor:
Intradductalpapillarymucinousneooplasm
75%%ofallpancreaticcysts.Walledoffareaof Inadolescentgirrls/youngwomen
Cysts:
panncreaticnecrosishemorrhagiccnecrotictissue solidandcysticczones,filled
Nonneoplastic
+ennzymes.Solitary(230cm).Onn/in/near w/hemorrhagicdebris,papillary
usually
panncreas.Walloffibrous+granulationtissue.No heets.B
projectionsorsh
unilocular.
epittheliallining.Duetoacutepan
ncreatitis(~6wks catenon/APCpathwayaltered.
Neoplasticusually
possttrauma)orinthesettingofcchronicETOH Benignglycogenrichlow wcuboidalcells Mostlyinwomen.Canbebe enignormalig.Arise
multilocular Cystw
w/mucus,canbebenignormalig.More
panncreatitis.Sometimesresolveaanddisappear, surroundingsmallcystsw w/clearstrawcoloredfluid. inbody/tail,painless,slowgrrowing.Contain
inMEEN,headofpancreas.
mosstcanbeeliminatedbysurgicaaldrainage 2Xmoreinwomenin70ss.Nonspecificsx mucin.Lookforinvasiontosseeifmalig
PancreatticDuctalAdenocarcinoma Morphology:60 0%ariseinheadofpancreas.2 20%inentiregland,15%body, 5%tail.Hard,stellategray/wh hitemass(desmoplasticstromaalresponse).Poorly
Solidtum
mors,ariseinductcells.Progressfromnonneoplasticepitheliumintraepithelialneoplasia(PanIN) defined.Inhead dobstructcommonbileductjaundice).Inbody/tailissillentuntillate.Caninvadeearlyintoextrapancreatictissues,adjacent
orinvasivvecarcinoma.Precursorsepiithelialtelomereshorteningmaaypredisposetoaccumulationof organs/nerves/rregionallymphnodes.Canmettastasizetoliver,lung,bones. Overall5yrsurvivalis<5%!Fo ormmalignantductstructuresveryHARD(abortive,
Pancreatic chromoso omalmutations.Activationofoncogenes(KRASin>90%ofcaases),inactivationoftumorsup ppressor irregular,small)..Anaplasticcuboidalcolumnarcells.Secretemucin.DesmooplasticStromalresponse.Perrineuralinvasion++.Lymphatiicandbloodvessel
st
Carcinoma genes(p11695%,SMAD4BRCA2p53).Accumulationismoreimporttantthantheexactsequence. Cause: invasion.Cliniccalfeatures:silent,sxappeartoolate.Painis1 sx(perineurralinvasionlink).Wtloss,anorrexia,malaise,weakness.Obsttructivejaundice(head).
notwelluunderstood.Age6080yo,M> >F(2:1),Blacks>whites,Jewish
hslightrisk.Smoking2Xrrisk,Not Migratorythrom mbophlebitis(Trousseausignoffmalignancy)in10%thromboosesform,resolve,reappearin ndifferentsitestumorreleaseeofnecrotictissue,
sureabou utdiet,alcohol,DM,chronicpaancreatitis.Hereditarypancreaatitis(PRSS1,SPINK1risk50XX).Puetz othersubstance es.Dx:endoscopicultrasound,CTimaging.Tumormarkerscaanmonitor(butnotdetect/screeen)diseaseCEA,CA199ag.Prognosis:poor
Jehger=>100Xrisk,inheritedcancersyyndromes(BRCA2AshkenaziJJews,p16CDKN2Agene) becauseoflated dx,<20%areresectableatdx.
DrugsListt
Drug Category MOA//USE PK SE
Oraladmin,butnotactiveuntil
O distalGItractbecauseofazoliink(activatedbyGI N/V
V,hepatotoxic,bonemarrowssuppression,reversibleoligospe
ermia
Sulfasalazine bacteria)Convertedtosulfapyraadine+5aminosalicylicacid Sulfaallergies
5ASAderivativemayinhibitIl1/TNF
Delayedreleaseformreleasedt
D throughsmallintestineandcoloon
a,inhibitLOX,scavenggefree IBDrem
missionusefulnessinCrohnscontroversial,helpfulin MoorewelltoleratedthansulfasallazineSErelativelyinfrequentt/minor.
Mesalamine radicals/oxidants,inhibitNFkB(but UC
pHsensitiveformreleasedinterminalileum/colon
Heaadache,dyspepsia,skinrashm
mostcommon.Assocw/interstitialnephritis.
Rapidabsorption,butmostislostinthestool
theyarentsure)
Assecondgeneration5ASAcreaatedtotrytodiminishSE
Olsalazine Oraladmin,anASAprodrug(act
O tiveinlargeintestine,bypassssmallintestine)
Diaarrhea,rarelynephrotoxicity
Canbeusedtopreventbleedingofessophagealvaricesincirrhosis.Blocksbeta2receptorsof Nausea,diarrhea,bronchospasm,,dyspnea,coldextremities,Ray ynauds
AdrenergicAntagonisst(Bblocker
Propranolol sympathetictone)
theme
esentericarteriolesresultinginunopposedalphavasoconstricctionreducingbloodflowto Oraladmin,verylipophilic(hhighfirstpasseffect) exaacerbation,bradycardia,hypoteension,heartfailure,heartblock,fatigue,
mesentterywhichreducesportalHTN. dizziness,concentration,halluccinations,insomnia
Pep pticulcersw/longtermuse,GIbleeds,uricacidretention,sa
aliicylism,
NonselectiveNSAIDa InhibitssCOX1and2toinhibitPGE2syynthesis.BlocksmucussecretiionstimulatedbyPGs,
Oraladmin otootoxicity,hepatotoxicity,nephrrotoxicity
(Ketorolac) blocksacidinhibitionbyPGs.Causesacidsecretioningut
Analgesicantiinflamm
matories Can ncausebigGIproblemssincen
notselective
COX2NSAIDs SelectivvelyblockCOX2toinhibitPGsyynthesisininflammationbutdoesntblockCOX1this Carrdiovaculardisease,thromboticevents,profuseGIbleeds,edema,elevated
Oraladmin
(celecoxib) meanslesserosionofGImucosa,lesssinhibitionofplateletaggregattion BP,,allergicrxns.
TripletherapyforHpyylori=(PPI),Metronidazole,AmoxicillinorTetracyccline,BismuthPleaseMakeTummyBetter)
Antibacterial:bindsbacterialtoxins(Bisthmus)
Bismuthsubsalicylaate Larrgedosescancausebismuthorrsalicylatetoxicity
Cytoprotectant:coattsirritatedmucosa Usedfordiarrhea,indigestion,abdo
ominalcramps Suspensionadmin
(Peptobismol) Blaackstools/tongue.CancauseR
Reyessyndromeinkids.
Antiinflammatory(suubsalicylate)
Binds30Sribosometo opreventproteinsynthesis OralorIV.Absorptionblockkedbyfood,milk, Teeethstaining/hypoplasiainchild
dren,Photosensitivity
Tetracycline Bacteriostatic,Broadspectrum(G+/)
UsedforHpylori,vibrio,coxiella,E.histolytica,spirochetes
Mg/Casalts.Renalexcretionn CIiinpregnantwomenandyoungchildren
Oraladmin,widedistributionnexceptCNS(only
Betalactam:Inhibitsccrosslinkingofpeptidoglycanccellwallbybinding Alleergy,neurotoxicityifinflammation,seizures,plateletdyxfx,G
GIdisturbance,
Amoxicillin w/penicillinbindingp
protein.Blockstranspeptidasess
Exten
ndedspectrumHpylori,G+/ cocci,G+rods,spirochetes. thereininflammation).Elim
mviaactiverenal
nepphritis
tubularsecretion.
Usew
w/anaerobicbacteria,H.pylori,,C.Difficile,bactrioides, Neurotoxicity,nausea,diarrhea,ccystitis,allergy,metallictaste,ttransient
BreaksdownDNAbyintroducingnitroradicalswhichcausecytotoxic
Metronidazole effect(pyruvadeferre
edoxinoxidoreductase).
anaerrobicprotozoa,trichomonas(m
mosteffectiveforgiardia, Oraladmin(gelformforrosaacea) leu
ucopenia/thrombocytopenia, anticoagulanteffectofwarfarin.Has
entam
moeba,trichomonas) disulfiramlikerxnw/ETOH.
Binds50Stoblockpeptidyltransferaseactivityinh
hibitstranslocation, Oral,IV
Ciarithromycin bacteriostatic
Usew
w/Hpylori
Metabolizedviacp450(CIw/
w/statins)
Sto
omatitis,heartburn,N/D,anoreexia,peristalsis(abdominald
discomfort).
IVforinfections(pneumoniaa,sepsis)
Vancomycin Blockspeptidoglycansynthesistoinhibitcellwallbu
uilding G+baacteriaCdifficile.
OralforCdiff
Flushing,nephrotoxic(rare),ototoxic(rare)
nd
2 genfluoroquinolone:inhibitDNAsynthesisbyinhibiting Oral Artthropathy,damagetojointdevvelopmentinchildren,adultten
ndinitis,some
Ciprofloxacin topoisomerase/gyrasee
Gbaacteria,UTI
Poorabsorptionwhentakennw/antacids pro
olongedQTintervals,GIupset,convulsions.
Loperamide(Imodium) MuopiioidreceptoragonistinhibitN
NO/VIPreleasetoblockrelaxattionbelowfoodbolus.
DoesntcrossBBB(soabusepotentiallimited) Craamps,nausea
Nonppropulsivemotilityspastic,uncoordinatedcontractionsresult LimitedBBBcrossingHasabbusepotentialandcan
Parradoxicalinmotilitybutp arrhealatlow
propulsions.Iseffectiveantidia
Diphenoxylate Antidiaarrheal causeeuporia.Adminw/atrrophinecanreduce
dosses(highercauseeuphoria,abuusepotential)
Antidiarrhealdrugs/a antivisceral potentialforaddiction.
hypersensitivitydruggs:Diarrhearesults 5HT3re eceptorantagonistpreventssensorynerveactivatedexcitattion/activationofmotor
Sevvereconstipation,ischemiccolitisfromfecolithobstruction
Alosetron frompropulsion,enhancedH2O& reflexes.Reducespain/cramping Oraladmin,rapidaction,liveermetab
CI:constipationpredominantIBS,,IBSw/mixedsx
electrolytesecretion,orboth.Caused Relieveessxinfemalediarrheapredom minantIBS.
byinfectiousagents,inflammatory CentrallyactingSNSinhibitionbutinw wallofgut,itisanA2adrenerggicagonistinhibitsAch
boweldisease,thyroiddisordersordrug releaseefrommotornervessupplyingggutmmlayers.Mimicseffecto ofsympatheticnn(actsat Hyppotension,drowsiness,constip eadache,
pation,drymouth,dizziness,he
Clonidine a2toin
nhibitAch,VIPrelease)soitinhibitspropulsivemotilitytoo
Oralortransdermal
fatigue/weakness,withdrawalsynndrome
effects.DiarrheaisaaSx,notadz.
Therefore,treatunde erlyingcause&use Hasbeenusedtotxdiarrheapredom minantIBS
Nortriptiline thesedrugssparingly BlocksNEreuptake,secondaryamine e
Desipramine ATCA
usedfordiarrhea,depression
n Oral.SometolerancetoSE, ECGrequiredprior Carrdiacdysrhythmiasw/overdosee,drymouth,blurredvision,urrinaryretention,
BlocksNE/5HTreuptake,a1/Mantago onist,tertiaryamine to/duringtx.Overdosedangger. nstipation,sedation,wtgain,orthostatichypotension/dizziness,sexualdysfx.
con
Amitryptiline ATCA
usedfordiarrhea,depression n,fibromyalgia,IBS
Macrollideantibiotic,butalsoaverysselectivepotentmotilinrecepto
oragonistcauses Con ncernsaboutdevelopingantibioticresistancethemotilidessarebeing
Erythromycin contracctionofsmoothmm,usew/van ncomycinforC.diff. Oraladmin creeatedasanalogstoerythromyccintosolvethisproblemsame eeffect,no
Prokinetics:Someuse espostsurgical Treatsconstipation anttibacterialactivity.Cramps,diaarrhea
ileus,delayedgastricemptying HR,blurredvision,constrictedbronchioles
MuscarriniccholinergicAch(M3)agon nistonthemmtostimulateconntraction Canadministerparenterally,,butuseorallyto
Bethanechol associatedw/diabeticcneuropathies,
eallyuseinahospitalsettingwheretryingtotreatpostsurgeryduetoSE.
Onlyre avoidCV/respiratorycompliccations
hoot as a hare, blind as a bat, d dry as a bone, red as a beet, and mad as a
GERD,functionalconsstipation(IBS) hattter
D2antaagonistonperipheralnerves.(leadstoAchreleasefromprresynterminal).Tightens NotapprovedinUSA.DoesntcauseParkinsonianlikesyndromesfromD2
Domperidone LESand dfacilitatesgastricemptying.O
Onlyhelpsw/upperGItractpro
oblems.
LimitedBBBpermeability
anttagonistactionbecauseitdoessntgettobrain.
5HT4re eceptorsagonist(enhancesAchrelease) Parrkinsonianlikesyndromesfrom mD2antagonistaction(EPSsideeffects)
Metoclopramide Periphe eralD2antagonist(leadsto Achreleasefrompresynterminal).TightensLESand PermeatesBBB Hyp perprolactinemia>amenorrheaa,galactorrhea
facilitattesgastricemptying.Alsohelpw/lowerGItractproblems.Anntiemetic. Agiitation,insomnia,anxiety,drow wsiness
Hyp onlikeSElisted
potensionmanycholinergicSSE(diarrhea,salivation,urinatio
Neostigmine AchEin
nhibitortoprolongAchexposuretoreceptorsexcitesthemm
mtopromotemotility. Usuallyusepostsurgicallyd uetoSE
forrbethanecol)
Methylnaltrexone DoesntcrossBBB.Doesntbblockanalgesiceffects
GIopiaate(u)receptorantagonist
likeNaloxonewould.Canussetotreat
Treatp
postsurgicalileus,constipiation
n,gastroparesis,beingevaluate
edforuseinidiopathic Can
ncauseN/V,buttolerancedevvelopsovertime.
Alvimopan constipationanawfulSEasssociatedwithopiate
constippation
use.24hrrelief.
Inhibitpeptidechaininitiation,stimullatemRNAdegradation,inhibittelongation,induceNKcells Thrrombocytopenia,bonemarrow wsuppression,leucopenia/anem mia,liver
Interferon Ifna:He
epB/C,posttransplantCMV,ge enitalwarts,tumors 1/wkinjection enzzymes,CNStoxicity(depression n,lunginfiltrates,flulike,autoimmune,
Ifnb:M
MS alo
opecia
Antivirals Nucleoosideantimetaboliteguanosin neanalogthatinhibitssynthesisofGTP,viralmRNA Red ducedrbcfromhemolysis,myeelosuppression
Ribavirin HepC,usew/pegylatedIfn,RSV
Oraladmin
CIiinpregnancyteratogenic
NRTI(nnucleosideRTinhibitor)termiinatesDNAchainelongation Hepatotoxic,resistancein1yr(200%),headache,nausea,pancreatitis(kids),80%
Lamivudine HepB,HIV
Oraladmin
havverecurrencew/discontinuatio onofdrug
DrugsList,Continued
Drug Category MOA/USE PK SE
Helpsdigestproteins,starches,fats.Containslipase,amylase,protease(trypsin). Entericformcoatedforreplacement(sonotbrokendownby
Pancrease Pancreaticreplacement Useinexocrinepancreaticinsufficiency,CF,chronicpancreatitis,blockedbileduct, gastricacid)mayneedtouseH2blockeraswelltoallowit Hyperuricemia(gout),hyperuricosuria,allergicrxns,GIupset
steatorrhea nottobreakdown
NeurotransmitterReleaseinhibitor
pancreaticsecretions(bigtimeinhibitorydrug)InhibitsgastrinreleasefromGcellsinantrum,inhibitsCCKsecretion,inhibits
Nausea,cramping,diarrhea,vomiting,fatty/loosestools,cholethiasis,HA,
Somatostatin H+productionbyparietalcells,inhibitshistaminereleasefromECLcells.Inhibitssecretionofpituitary/pancreatichormones,
SCorIMadmin dizziness,fatigue,hyper/hypoglycemia,hypothyroidism,galactorrhea,flushing.
(octreotide) GIhormonesecretionandGH/IGF1secretion;inhibits5HTreleaseforsxreliefofcarcinoidtumors.
RecommendedtomonitorVitaminB12.
Canbeusedtotreatesophagealhemorrhagesinhibitsvasodilatorymediatorstocausevasoconstrictionofmesentericblood
vesselstherebyreducingbloodflowandportalpressures.
Shortduration,fastonset.Canchelate,effectivenessof Becarefulwithalloftheseifpthaskidneyproblems(hardforthemtopassthe
CaCO3(Tums) Antacid:Chemicallyneutralize CaCO3+2HClCaCl2+H2O
otherdrugs(liketetracycline) ions)otherwiseprettysafeshortterm.Hypercalcemia,reboundacid
stomachacidraiseGIpHtorelieve
painofdyspepsia,acidindigestion, Constipation,alluminimumamountoffeces,hypophosphatemia,proximal
Al(OH)3 Al(OH)3+HClAlCl3+3H2O Longduration,slowonset
mmweakness,osteodystrophy,seizures
enablepepticulcerstoheal.Mostly
Mg(OH)2(milkof hydroxidebasesassociatedw/various ProducesdiarrheaagoodlaxativeMg=MustGotothebathroom.
Mg(OH)2+HClMgCl2+2H20 Shortduration,moderateonset
magnesia) cations Hyporeflexia,hypotension,cardiacarrest

Neutralizesacid,pepsidinhibitionfrompH(sameasallothersabove,Ijustdont
NaHCO3 Allcausehypokalemia
knowthechem.equation)
Shortduration,fastonset Metabolicalkalosis

Bifidobacterium
Probioticagents:seemtosuppress
infantis systemicinflammation,feelingsof
Mechanismnotreallyunderstooddothebacteriaoutcompeteinfectious
VSL#3 bloating,andimprovemild
pathogen?Dotheysubduethereleaseofinflammatoryfactors?Wearentsure.
Oral Nonethattheyreallytalkedabout
diarrhea/constipationasassociated
Lectobacilus withlowlevelentericinfection
plantarum
Oraladmin,urineelim
Opioidagonist(mu,kappa) CrossesBBB(addictivepotential) Tremor,seizures.Cautioninrenalfailurebuildupofmetabolite
Meperidine NarcoticAnalgesia
Painmed. Givenaloxene(opiumreceptorantagonist)tocounter normeperidinecancauseseizures.Drymouth,sorethroat,constipation.
overdose
MildextrapyramidalSE(canreversew/muscarinicantaglikebenztropine)
Dareceptorantagonist(phenothiazine)bindD2receptor(andD1,a1,M1,H1).
dystonias,tardivedyskinesia,parkinsonism,sedation,hypotension,
Chlorpromazine Antipsychotic,centralstimulantblocking,antiemeticbyinhibitingNSTandCTZ
hyperprolactinemia,neurolepticmaligsyndrome(rareemotionaldetachment,
Usedforchemoassocemesis,palliativeforschizo,mania
OralorIM(highlylipophilic) affectiveindifference),sexualdysfx.
Droperidol Antiemeticdrugs:workinCNSat QTprolongedw/droperidol,EPS(high),sedation/hypotension,
D2antagonistantiemeticbyinhibitingNSTandCTZ
vomitingcenter(areapostrema,NTS, hyperprolactinemia,sexualdysfx.Tolerancetosedation/hypotensiondevelops,
Haloperidol Usedforchemoassocemesis,schizo,mania(bipolar)
CTZ).Canbeusedtotxchemotx nodependenceorabusepotential,highpotency
inducedemesis(acutein24hrsdrugs Da/5HT3antagonist,weak5HT4agonistforAchrelease.WorksinCTZ/NSTas
Agitation,insomnia,anxiety,drowsiness,EPS,hyperprolactinemia>amenorrhea,
Metoclopramide mosteffectivehere,delayeddrugs antiemetic,GImotility
galactorrhea.Stimulatessmallandlargeintestinemotility.
notaseffective,anticipatoryless Usedforchemoassocemesis,GERD,postsurgileus
Ondansetron severewhenacuteemesisistreated
5HT3receptorantagonistonafferentnerveendingsinGImucosa,central5HT
effectively). CanbeoralorIV Relativelysafe,fewSEconstipation(occasional),HA,lightheadedness,
Dolasetron blockinNST/CTZ
Livermetab prolongedQT(minor)
UsedforchemoassocemesisYouwontvomitsoyoucangoONDANSing
Granisetron
SyntheticmarijuanaactsatCB1receptorssuppressesneuronsinarea
Dronebinol postrema.Alsostimulatesappetite.
MakesareallysickpatientfeelaLOTbetter
Intheacidicenvironmentofthestomachbecomesnegativelychargedandturns
Difficulttousehavetowaitforulcertohealbeforeyouuse
intoaviscousgelformingaprotectivebarriertopromotehealing.Notreallyused
Sucralfate Cytoprotectants:PGsinhibitacid atonnow,maybeinburnpts.Thinkofitlikeachemicalbandaidthatallows
anyacidsuppressiondrugs(sinceitneedsacidtowork) Constipation,assocw/bezoarformation
Locallyacting,shorthalflife
secretionandstimulatebicarb/mucous ulcertoheal.UsedforulcersnotcausedbyNSAIDuse.Helppreventrecurrence.
secretion.Neededtoprotectthe AstablePGE1analogusedtotxpepticulcerdisease,especiallythatassociated
stomachwhenPGsarebrokendown w/useofNSAIDs.ActsonEP3receptortostimulatebicarb/mucoussecretion,
Diarrhea,cramping,menstrualirregularities,
Misoprostol (NSAIDs,etc) cAMP/inhibitsacidsecretioninparietalcells,mucosalbloodflow ShortT
CIinpregnancy!Abortioninpregnantwomen.
UsedtopreventNSAIDinducedulceration,maintainpatentductusarteriosus,
inducelabor
Glucocorticoids:IBD(bothCrohnsand Cataboliceffectinducesnewproteinsynthesis,GNG,lipolysis,peripheral
Prednisone UC)oftenabletoinduceremissionbut glucoseuse.Antiinflammatory,immunosuppressant SE:Osteoporosis,Cushingoidrxn,Psychosis,Glucoseintolerance,
Oral
lessvaluableinmaintainingremission, Infection,HTN,Cataracts,longtermusehasnomaintenancebenefit
Budesonide especiallywithoutcausingtoxicity
Hasaffinityforglucocorticoidreceptor50100Xgreaterthanprednisone
Unknownmechproposedtoimprovehealthandrecoveryfromillnessandtxof
HepC.Aphrodesiac,improveenergy,reducestress,improvementalperformance. Oral
Ginseng Evidencedoesntsupportclaims.Maybeusefulindiabeticstocontrolblood Interactsw/phenelzineHA
Headache,GIupset,hypoglycemia,sleepdisturbances
sugars
InducescytP450!!!Preparationsnotstandardized
Herbalproducts Usedformilddepression.Hypericinisactiveingredient.EffectsequaltoTCAsin SimilartoSSRIs:Photosensitivity,drymouth,dizziness,majorGIupset,Di
St.Johnswort someclinicalstudies,lowgradeevidenceforotherbenefits
Interactsw/alotofmedsdigoxin,oralcontraceptives,
w/cP450
warfarin,indinavir,loperimide,omeprazole,
GradeBevidencefortxofchronichepatitisorcirrhosis(alcoholicorotherwise), Cautioninptsw/diabetesorhypoglycemiamayactasphytoestrogenand
MilkThistle
andgallbladder.Moststudiesshowedimprovementinliverfxtestsovertime. Oral shouldbeavoidedbypregnantwomenandptsw/hormonesensitivecancers.
(Silymanin) Antidotefordeathcapmushroom(amanitaphalloides) Laxativeeffect,upsetstomach,diarrhea,bloating,allergicrxns
TNFamonoclonalab.
Infliximab UsefulbecauseTNFaisexpressedinCrohns,alsousedinRA
IVinfusion
Fever,chills,fatigue,hypersensitivity,riskofinfections/malignancies
Monoclonalabs TNFamonoclonalab,DMARD
ShouldobtainaTBtestbeforestartingtx(canallowreactivationtb)
Adalimumab(Humira) UsefulbecauseTNFaisexpressedinCrohns(alsousedinjuvenileRA,ankylosing SCinjection
spondylitis)

DrugsListt,Continued
d
Drug Category MOA//USE PK SE
Omeprazole H/KATTPaseformscovalentbondwith hactiveformofdrugthatcomp
pletely Inactiveun ntilithitsacidicenvironmentoofthestomach
Lansoprazole inactivaatesthedrug.IrreversiblyinacctivatesH/KATPasechannelandnewones sulfonylgrrouposcillatesbetweensulfonaamideandsulfenic VirttuallyfreeofSE(onlyactivated
dinstomach).Stateoftheartfortxofulcers,
Protonpumpinhibito
ors:
Pantoprazole havetoobecreatedbeforetheirfxreturnsforacidsecretion acid.Sulfeenicacidisactiveformofdrug..Verypowerful,only etcc.CanhaveMMC.B12ab bsorption,bacterialgrowth
Use:peepticulcer,gastritis,esophageaalreflux,ZES 1doseperrdayisneeded
Rabeprazole
PurineanaloginhibitDNA/RNAsyntthesisbyinhibitingfirststepindenovopurine
6Mercaptopurine synthesis,metabolizedbyxanthineoxxidase DI:Allopurrinol(whichinhibitsxanthineooxidase,lowerby75% Hepatotoxicityjaundice,bonem
marrowsuppression,immunosu
uppression,GI
UseA
ALL,CML,IBD orelseseeetoxicities) distturbances
Azathioprine Metabo
olizedto6mercaptopurine(so
osamemech).UseIBD
FolicaacidantagonistblockTHFFsynthesisbyinhibitingDH
HFR,lackof
Immunosuppressantss Accumulattesinfluid Moouthulcers,GItoxicity,hepatottoxicity,nephrotoxicity,alopecia,bonemarrow
THFinnterferesw/dTMPandden novosynthesisdiminishD DNA
Methotrexate replicaationinSphase
Weeklyinggestion(IMorSC),Takessevera
ralweeks. sup
ppression.Cautioninedemaan ndrenalfailurecanaccumulatedoses.
Renalelim
m Leu
ucovorinusedtorescuenormalcellsinbonemarrow.
UseA ALL,AML,NHL,choriocarcinoma,osteosarcoma,RA,IBD
Calcine
eurininhibitorblockslymphoccyteactivation
Cyclosporine UseC
nd
Crohnsdisease(2 line)
Addedafteerinitial710daysofIVhighdoosecorticosteroids Nephrotoxic,hyperkalemia,HTN,gingivalhyperplasia

Bran
Bulkfo
ormingwhenabolusgetsinto ocolon,itabsorbswater,disten
ndsthecolon, 13daysto
oeffect.Usedasanadjuncttoodietary/behavioral
Psyllium activatespolarizedreflexestostimulaateperistalsis. changes,aacutetxafteranalrectalsurgerry
Methylcellulose Obstructionifyoudontproperlyhydrate
Laxatives:constipatio
oncanresultfrom
Bisacodyl StimulaantdirectlystimulatecAMPforwater/electrolytesecretion getsemi
adisruptionofnormaal
fluidstools.Widelyusedandsometim
mesabusedbypts.Butoktou
usefor 68hoursttoeffect.Semifluidstools
Anthraquinones absorptive/secretorybalanceand/or
occasioonalconstipation.
alteredmotility,abuseoflaxatives.
Magnesiumcitrateor Besttotxunderlyingcause.Useprior
Salineosmotic.Waterevacuation(SEEVERE)souseisreallylimitedd.Usedto
sulfate tocolonoscopy.
preparebowelforcolonoscopy(cleannitoutcompletely)resultisEXPLOSIVE 13hoursttoeffect Fluid/electrolytedepletion
Lactulose
Helpso
openClC2tosecreteCl.Watermovesintolumenusedtottreatchronic
Lubiprostone constip
pation
Oral Noproblemsw/tolerance,dependency,orelectrolyteimbalance
K+sparingdiuretic,AldosteroneantagonistatDCT,U
Usedfordieresis Hypperkalemia,gynecomastia,imppotence,GIdisturbances,metabolicacidosis,
Spironolactone Canbeusedw/furosimidetotreatascites
AvoidK+supplements,dontuseinrenallfailure.
loselotsofNa/waterinurine
Cimetidine H2Antagonists:blockkH2receptorsonparietalcellsashistaminefacilitatesH+se
ecretion Theleastpotento
ofH2blockers Anttiandrogenic(gynecomastia)++alllistedbelow
Ranitidine causedbyothersecre
etagogues,H2blockersareeffe ectiveinreducingH+secretionin
responsetoanysecre
etagogue.H2antagonistsareu usedinitiallyforthepharmacologicaltx MorepotentthannCimetidine,
enal
P4550inhibition.Diarrhea,headacches.Needtoreducedoseifre
Nizatidine ofgastroduodenalulcersandGERD(inexpensive).UseofH2blockersshouldbe butwithfewerSE.Allavailable Longerhalflivesthancimetidine
insufficiency.
OTC.
Famoticine accompaniedbylifesttylechanges.
AcetominophenusesupGSHalcoholmakesthisw worse.ThisdrugGSHandbinndstoxins,
Nacetylcysteine preventsliverdamage e. IVadmin N/V
V,anaphylacticrxn.
Txforacetaminophen noverdosew/prompttx
Glutathioneprecursorprovidesprotectiontooxidaativestress.SAMisreducedin nalcoholicliver
Liverprotectants disease.WeakandinconsistentevidencehintsthatSAMemightbehelpfulforavaarietyofliver e,hives,stomach
Serriousallergicrxnclosedthroaat,swellingoflips,tongue,face
Sadenosyl conditionssuchascirrhosis,chronicviralhepatitis,p
pregnancyrelatedjaundice,andGilbert's achhne,nausea,diarrhea,gas,anxiety,spasms,insomnia
Oralsupplement
methionine syndrome.Thebodym makesalltheSAMeitneeds,so othereisnodietaryrequireme
ent.However,
deficienciesinmethio
onine,folate,orvitaminB12can nreduceSAMelevels.SAMeisnotfoundin CIiifpregnantorbreastfeeding
appreciablequantitiesinfoods,soitmustbetakenaasasupplement.

DrugDrugInteractionss,metab
Ptfactors:diseasestatte,renalfx,hepaticfx,seru
umproteinconc,food,
env,useofalcohol/tob bacco,genetics,age,gendeer
Riskfactors:drugsw/n narrowtherapeuticindicess(doseresponsecurve
shiftedleft),administrrationoflarge#ofdrugs,criticalillness,HIV
infection,substanceab buse
CYP450interactions:
Phase1metab((addgrouptocompound oxidations,
reductions,hydrrolysis)CYPsdooxidation nreaction(alsoFMOs,
MAOs,XO,etc).
o ReactionofCYP450:Drug+2NADPH H+O2DrugOH+
NADP++H2O
CYYP450s:afamilyofenzyme esthatoxidizedrugs.
M
Manyisoformsexist.Inmosthumans,catalyzed
byyCYP3A,CYP2D6,CYP2C,C CYP1A2,CYP2E1.
M
Manydrugdruginteractionsthrough
in
nhibition/induction.Altere
edhepaticbloodflow
caanaffectdrugmetabol(proopranolol)
Caanmakedrugsmoreorlessstoxic(dependingon
th
hepathwayandwhatthem metabolitesare)
Exxofinducers:Phenobarbital,carbamazepine,
Ciigarettes,ETOH,phenytoin n,Rifampin
nhibitors:Allopurinol,cimetidine,ciprofloxacin,
In
clarithromycinetc
o GrapefruiitjuiceinhibitshepaticanddintestinalCYPs
responsib blefor1stpassmetabofsomedrugs(dueto
furanocou umarineslikebergamottin)getCmaxand
AUC.Can nalsoinhibitorganicaniontransporting
polypeptide,Pglycoproteintranspo ortofdrugsinGI
epithel.(exfelodipine,cyclosporine,tacrolimus,statins,
buspironee,carbamezepine,diazepam,midazolam,
triazolam,,methadone,sildenafil,niffedipine)
o
Phase2:conjugaationsw/glutathione,glucuronicacid,sulfate,
acetate,methyl,,etc
Eliminatedviametaab:ETOHacetaldehyde Alcoholblooddiisappearanceiszeroorderr.Fastingalcohol Ethanoldruginteractionexample:
acetate(Krebbsccycle)H20+CO2 dehydrogenase. Expectexceesssedation(interactw/se
edative
Alcoholdehydrogen nases: Adverseeffectsofethanoldependondoseeandfreqofconsumption n. hypnotics,aantidepressants,neurolepttics,sedating
o HumanADHiscytosolic,containsZn.2 20 antihistamines,narcotics)
isozymescoddedin5genes,allprettysm
mall. Effectsonliver:NADH/NADratio,aceetaldehydeconc,steatosiss, Interferesw
w/metab(inhibitscertainC
CYPs,induces
Lotsofpolym
morphisms(leadtodifferen nces proteinaccum, proteinexport,produuctionofcoagfactors, others)in
nterferesw/warfarin,hypoglycemic
amongindividuals) watercontent, watercontent,oxygeenuptake(centrilobular sulfonylureas,acetaminophen,otherss
o ETOHlosesanelectrontoNAD:ETOH+ + hypoxia),prolifeerationofER(CYPconceentration,ordrug Somedrugsscauseaccumofacetaldeh hydefrom
NAD+Acetetaldehyde+NADH.Canget metab),producttionoffreeradicalsandlippidperoxidation,collageen ETOHmetab(metronidazole,sulfonyllureas,
excessNADH(shiftinglactate/pyruvateratio) deposition(scarring,cirrhosis),hepatitis,ccelldeath n,cephalosporins,chloramphenicol)
griseofulvin
MEOS(microsomalethanoloxidizingsystem)= CanriskofGIbleedfromNSAIDs
CYP2E1residesinSER,requiresO2+NADPH H, Extrahepaticeffeects:GI(gastritis,pepticullcer),pancreatitis,heart
producesacetaldeh hyde,NADP,andH2O.Only (vasodilation,caardiomyopathy,arrhythmiaas),portalHTN,endocrine
doesabout10%ofalcoholmetab (feminization),ccancer(upperGI,liver),fettalalcoholsyndrome,acutee
Catalase:inperoxisomes:ETOH+H2O2 depressant,chro onicWKsyndrome,imm munecompromise
acetaldehyde+H2O O(probablycontributesvery
little)
(acetaminophen==APAPinthisslide).
Overtime,depletionofglutathionecausesN NAPQIbuild
upbindstothingslikeproteinsinliverfo
orm
macromoleculestthatcanleadtonecrosis.
CYP2E1isaffecteddbyETOH:competitiveinh hibitionor
inductionCYP2E1canoccurwhenethanolistakenin,
getmoreproteinfor2E1
ss
Acetaldehydeoxidation:e efficientinmetabolizing
acetaldehyde.2classes lowKmALDH2(in
mitochondria,doesmostmetab),highKmALDHs1//3/4
(incytosol)
Inhibitors:disulfuraam,daidzin(unpleasantrxnnof
periphvasodilation,sweating,headache,naussea,
vomiting)
50%ofAsianshaveinactivegeneticvariantoff

ALDH2slowerme etab,lowincidenceof
Ethanolmetab/toxicityy
alcoholism
Rapidlyabsorbeed.
Liverisorganoff1stpass.

BugsList
Normalfloraofth
he
GItract
Organism
EscherichiacoliETEC
C pathogenicforpigsonly;HumanETEChasC
(enterotoxigenic)
EscherichiacoliEHEC
C ShigatoxinsStx1//2;Hemolysins
(Enterohemorrhagic)
EscherichiacoliEPEC
C Noknownexotoxxins
(Enteropathogenic)
EschericiacoliEIEC
(Enteroinvasive)
EscherichiacoliEagggEC
(Enteroaggregative)
Salmonellaenteric
gastroenteritis
Salmonellaenteric
serotypeTyphityphoid lactose(clearon
fever
Mouth:heavilycolo onized,variesfromsitetositeAlpha Esophaggus:mostly Smallintestine:moreanaero obic Largeintestine:9095anaerobes.Feces byweightis
Stomach:sterrileifacidpromotesenzymes.OccasionallyseeG+sthat
streptococci,Streptococcusmutans,Neisseriasp,Diptheroids,S. transien
ntsfrom environment.Floraisscarce,,with 20%bacteeria.IncludesBifidobacterium,Eubacterium,
areacidresisttant(Streptococcus,Staphyloco occus,Lactobacillus,
aureus,S.epidermid dis,Lactobacilli,spirochetes,Mycoplasma;Lots mouthaandURT distancefromstomach.Mosstlyanaerobes Bacteroidees,Fusobacterium,Clostridium,Lactobacillus,
peptostreptoccoccus,fusobacterium,helicob bacter).
ofanaerobes:bacteroides,fusobacterium,clostridium, (veryfew
worganisms (Enterococci,peptostreptocoocci, Streptococcci,Enterococci(upto1%),Enterobacteriaceae
10^31 10^5pergramofcontents
peptostreptococcus ingenerral) Porphyromonas,Prevotella) (0.1%).100^1110^12pergram!Lots!
RolesofGIFlora:
Diarrhe ea:aninstoolmass,freque ency,and/orfluidityruns
excludingexogenouspathogenscolonizaationresistance(occupiesadh hesionsites,alters
Dysenttery:painful,frequent,smallvo olumestoolsw/fecalleukocytees(andblood)commonlycau usedbyShigelladysenteriaesquirts
physicochem micalenvironment,produceanttagonisticsubstanceslikebacte eriocins,useup
Noninnflammatorysecretory:viaenterotoxinand/oradherence/suuperficialinvasioninproximalsmallbowel.Causeswaterydiaarrhea.NOFECALLEUKOCYTES S.Exfood
availablenuttrients),
poisoningviapreformedtoxin,waterydiarrheafromproxsmallinttestine(Vibriocholerae).
developingimmmunefx(numberoflymph hocytesandplasmacellsinlam minapropria,size
Foodpoisoning:group,acuteN/V,timeofonsetveryshort((14hrs,preformedtoxin)maajoragentsareBaciluscereus,Staphaureus
ofPeyerspaatches,mesentericlymphnode es,spleen,thymus,m
Waterydiarrhealargevolum mesricewaterstools,oftendduetoproductionoftoxinsthattaffectsecretion/absorptionin nsmallintestinestarts13da
ayspostinfection
chemotactic//phagocyticactivity,productionofIgGandIgA),
andlastsseveraldays(choleraa)
developing/d differentiatingmucosalepithelium,
Rotavirus:Youngpt,3dayhx,nooneelseinfamilyhassx,pootentiallyexposedtoanotherssickchild
developingnnutritionalcapabilities,providinngnutrients,
Norovirus,:2dayslateracutteN/V/diarrhearelatedtoGRO OUPeatingFOOD.Nopus/RBC Cs,lasts12days.
providingvitamins:K(bacteroides,prorpionobac,enterococci,enterobac)),Folicacid
Exudattive(inflammatory)diarrhea:vviainvasion/cytotoxin,inflamm matoryresponsetriggeredincoolonleadingtodysentery/inflam mmatorydiarrhea.Stoolexamhasfecal
(bifidobacterrium,enterococci,Ecoli),B12((Ecoli,bifidobacterium,klebsieella,clostridium,
leukocyytes,sometimesRBCs(exshigella,EHEC,Salmonellaenteridditis,Campylobacter).Leukocyytesinstoolindicateinvasivepathogen(butlackdoesntruleitout)
fusobac),B2(Ecoli,citrobacter,Klebsiella),Biotin(Ecoli,bifidobacterium),Thiamine
Dysentery(shigella,EIEC,EHECC,campylobacter,somesalmoonella):Pus/blood,eatingtogetther.AcuteN/V,SEVEREabdom minalpain,frequent/smallvolu umediarrhea
(bifidobacterrium),Nicotinicacid(bifidobactterium),Pyridoxine(Bifidobactterium)
w/pus/blood,canlastseveralday
detoxofmatterials
Shigella:Daycare,spreadseassilytoothers(group),pus/bloodd,fever,tenesmus,slowlyproggressing(3days)
Disruptionofnorma alGImicrobiota:susceptibilitytoentericdisease,antibioticassocdiarrhea,
Giardia:Wtlossover2months,greasystoolsmostlyafterm meals,35waterystoolsdaily,hxofmountainstreams
andpseudomembraanouscolitisfromCdiff.Canch hangeentirepopulationofgutmicrofloraand
C.diff:45y/owoman,nosoco omial,dischargedw/maintenannceantibioticsafterelectivesurgery,nooneelseshowssx
thatisseenafter2wweeks
SystemmicDisease(entericfever):organismpenetratesthebloodsys ystemfromtheGItract.Startsinsmallbowelbutspreadstotthewholebody(exSalmonellatyphi,Yersinia
Jejunum:absorbs35Lwater/day,iliumabsorbs24L/day,colonabsorbs12L//day(canabsorb
enterocolitica).Sx:N/V,abdominalpaain,diarrhea/dysentery,fever((happenespeciallyw/orgthatcausecolitis,lowerinGItract)
6).Inseverediarrheea,canlose14L+ofwater.
Staining/Dx Virulence ClinicalPresenttation Epi
Fimbriaeconveyspecificity:K99strainspathogenicforcalves,lambs,pigs;K88strains
CFA,CS(colisurfaceag)
Hypersecretioninsmallintestine. Endemicinssomeareas
Exotoxins:
600millionccases
LT(labileto
oxinlikecholeratoxinA
ADPribosyltransferasethaattargetsGsandleadsto
AdheresviaCFAppili,butnoninvasive,noinflammation worldwideannually(800
elevatedcA AMPlevelsinintestinalepithelialcellswaterydiarrrhea),
thousanddeeathsin
ST(stablettoxinsmallpeptidetoxinthatbindsguanylatecyclaaseandcausescGMP
Travelersdiarrheaa(watery) children<5y
yrs)
samenete effectsasLT)
Toxingene esareencodedonaplasmaa(oftensameasCFA)
LargeGramnegrrod
Intiminadhesion,,T3SS,Tir Attaching/Effacingglesionsinlargeintestineformationofpedestalun nder Lowinnocula ativedose
Fermentslactose e
bacteria,lossofloocalmicrovilliandelongationofremainingmicrovillileadsto
Often0157:H7,b butotherserotypesalsoseen. lossofabsorptive capability. Undercookedbeef,milk,
TSI:yellow/yelloww
Doesntinvadeattachtoepithelium,insm mallbowel Hemorrhagiccolittis.Bloodydiarrhea,HUS.Stool:RBCs es
fruits,veggie
MAC:pink
Bundleformingp pili,Intimin,Type3SecretionSysteminjectstoxinsinntohostcells,Tir(abacteriial
HE:Orange(FLac/Suc) Attaching/Effacingglesionsinsmallintestine (formpedestalunderbactteria,lose
proteintranslocatedintoepithelialcellsbyatypeIIIsecretionsystem
m)
CNA:nogrowth localmicrovili,rem
mainingmicrovillielongatee) Infants
Oxidaseneg Causeswaterydiaarrheaininfants,sometravvellersdiarrhea.Diarrheaadueto Food/water
EPECadhesion:M MicrocolonyformationbyB Bfp(step1).ThenintimateeattachmentbyOMP
Indole:pink(+) damagetohostceellsanddisruptionofabsorption on
contaminatio
receptorbindingmediatedbyOMP(intim min)andreceptor(Tir).Baccteriaattachtoenterocytee
Tx:Usuallyselflim
mitingfluoroquinolones,bacim
membrane,injecttothereffects,disruptthe ehostcellapicalcytoskelettonandformpedestals
Invasiveincolonmucosalinvasion,localsppread(likeShigella) Children<5
WateryDysenttery,inflammatorydiarrhea(gastroenteritis) RareinUS
Invplasmidmobilegeneticelement
Tx:Usuallyselflim
mitingusefluoroquinolonnes,bactrim T:Oralfecal(food)
Stool:RBCsandPPMNs Humanreservoir
Bundleformingp pili Formsadherentbbiofilminsmallintestine
Hemolysin,ST,Ch holeraliketoxin(ST). Mucoidwaterydiaarrheainchildren(2wks),prolongedinAIDSpts.
Noknownexotoxxins Gastroenteritisinvvolvingsmallbowel(diarrh hea,nauseaw/fecalleuko ocytes)
LPS(Oagrepeatss)causesfever Duetodirecctdamagetoenterocytes//inflammatoryresponse
poultry,eggs
R:animals,p
TypeIIIsecretionsystems,invasinproteins(invAHgenes,others) 12dayslatterabdominalpain,N/V//Dfor34days
T:contaminaatedfood
Entryviatriggerandmembraneruffling(enterMcellsofsmallintesstineusingT3SStoinduce Somecauseecolitis(dysenteryw/pmnsandbloodinstool)
(raw/underccookedmeat,
membranerufflin ngandformationofphagosome,injecteffectorsthattmodifyphagosomeso Salmonellosis:Noontyphoidalorganismsten ndtocauseonlylocalized
y,milk),water.
eggs,poultry
bacteriacanmulttiplywithin).Liketomultip plyinPeyerpatches.Exoccytoseintolaminapropria inflammatoryrespponseindistalileumandcolon.Gastroenteritisdiarrhea.
Grod, (thereT3SSfacilittatessurvivalinms/killing).Stimulateslocalinflam
mmatoryresponse.Diseasee Bluntvilli,vascula rcongestion,inflammatio
on(watery)
Need>10^6cfu.
Motile duetoenterocyte esandinflammatoryrespo onsesmorethantoxins. Tx:Onlytxw/antibbioticsifothercompromissingillnesses(usuallydont
Fermentglucose,, Acidenvironmen ntofstomachturnsonexp pressionofvirulencegenes. recommendtxbeccausecarrierstate).Sto ool:PMN+
Oxidaseneg, Capcularags(Viaags)stopsPMNphagocyttosis Systemicinfectionentericfeverr(pain,diarrhea,dysenteryy,bacteremia,extraintestinalinfectionslow,lastsffor
Doesntferment Noknownexotoxxins weeks)..Rosespotsonabdomenandchestblanchonpressuure.Constipationthendiaarrhea(chronicinfectionofblood
LPScausesfever stream,,encephalopathy,infection natbiliarytree).Chronicccarriersmaygetgallbladdeerinfection.
Strictlyhuma anpathogen
Mac), TypeIIIsecretiontoinjectproteinsfrombacteriainto
Tropical(LatinAmerica,
H2S+ cytoplasm Typhoid dfever:
Asia,India),developing
Multipliessameaasgastroenteritisform(see eabove) Wk1:bacteremia,fever,ch
W hills
Usuallyfood
countries.U
GenesinducedbyylowO2tensionofgut.M Maybeinduced Wk2:mononuclearphagoc
W cytesrash,abdominalppain,prostration
borne
byacidpHinstommach Wk3:ulcerationofPeyers
W patches,intestinalbleedinng,shock.Cantraveltomesentericlymphnodesand dms
T:Oralfecal
Passthroughinteestinalepithelialcellsviatrranscytosis candisseminateinfectionbbodywidebacteremia,syystemic
w/minimalepithe elialdamage,enterlaminapropria(5 Stool:m
monocytes
10%leadtobacte eremia) Tx:fluid
d,electrolytes;canusechloramphenicol,ampicillin,,cephalosporins,quinalon nes
BugsList,continued
Shigellaspp(S. Facultativeanaerrobe
dysenteriae,S.sonneii,S. Nonmotile
flexneri)
Campylobacterjejuni
Clostridiumdifficile
Clostridiumperfringen
ns
Helicobacterpylori
Listeriamonocytogenees
Attachtolargein
ntestineMcells,triggerupttakeviareceptormediated dendocytosis(membrane
Intestinalepitheliaalcellskilledbyintracellulaar R:StricthummanpathogenNEVERco onsidered
ruffling)mediated dbyTypeIIIsecretionsysttemandIpaproteins(IpaAABCD)encodedonlarge22 20
multiplicationofbbacteria,shigatoxineffectss normalfloraa.
Kbinvasionplasmmid.Rapidly(<15min)escaapephagosomeintohostccellcytoplasm(IpaB/C/D
inflammatoryrespponsesurfaceerosions//ulcersin T:Oralfecal,especiallyinunderdeveloped
Grod requiredformp poresinphagosomememb brane).Onceincytoplasm,bacteriamultiply,spreadto
gutwall,acuteinfflammatorycolitis,bloody countries;mmostlyinyoungchildrenoffdeveloped.
otherepithelialcellsviaIcsABintracellularspread.Polymerizeshostcellactinatonepoleofceell
dysentery.Usuallyyinfectionsarelimitedtothe Outbreaksiindaycarecenters,mentalinstitutions,
andmovesthroughcytoplasmonactintails.Canspreadlaterallyfrromcelltocellthroughhosst
intestinalmucosallepitheliumandsubmucossa.Onset cruiseshipss.
Acidresistant epithelium,andccanmovethroughepitheliaallayertolaminapropria,w wheretheytriggerastrong
afewdays.1stw
waterydiarrhea,thenbloo ody(50%)
Doesntferment inflammatoryressponse
causeshemorrh agiccolitislikeIBD Highlyinfecctions(<200canleadtodissease)because
lactose(clearon
veryacidreesistant.
MAC) LPS,Shigatoxin(vverotoxinnotnecessaryfo ordisease,butcontributestoseverity)
ShigatoxininkidneeyscanHUS(alsoseeniinEHEC)
Closelyrelatedto
o Similartoxins(Stxx1/2)inEHEC.
~25,000cassesreported/yrinUS.>1/2 2inchildren
EIEC ABsubunittoxin
Tx:generallyselflimiting,butdehydrationccanbea <5yrsold.
bindsGb3globotriaosylceramidesonrenaltubularce
Bsubunitb ell,vascularcellson
severeproblem.H Hydration,fluoroquinolonees,
Hektoenagar kidney/braain/intestine,Pnethcellsinintestine.
bactrim(ifsuscepttible) Preventionsanitationnoeffectivevaccineyet
Asubunitisofthelargesubunitofhoostcellribosome,irreversiblydestroyingribosomalfxx,
althoughlivveattenuatedvaccinesund der
blockingprroteinsynthesis(leadstoccelldeath.Damagescapillaaryendothelium
Stool:rbcs,pmns investigation.
(microthroombiincolonandkidney HUShemolyticanemia)
Grodscurved(S
Invasiveaffectsjejunumtoanus(DISTALCOLON ).Mostcommonbacterialcauseofdiarrheaindeveeloped
shape),highlymo otile T:Lowinfecttivedose
enetratemucus.
LPS,flagellatope countries.Cryptitis,absccesses,,ulceration(needtoodifferentiatefromIBD).Lowerabdominalpaintod
diarrhea
Microaerophilic (<1000cfu)
inhours(wateryordyseentericw/blood/pus)+feveer.Resolvesspontaneouslyindaystoweeks,cangivve
(requirespecialm
media R:GItractso
ofanimals,
ndocyticvacuoles,thenasssociatesw/cell
Enterscellsviaen macrolides,fluoroquinolonesifsevere.
andgrowth uncookedpo oultry
microtubulenetw work. Diarrhea(canhap ppenevenifnoninvasivesttrain)
conditions42C,,low
Dysentery
O2). Mostcommo onbacterial
Cytolethaldistendingtoxinarrestscelldivissionbutcytoplasm Entericfeverifpro
oliferateslaminapropriaaandmesentericlymphnodees
Catalase+,Oxidase+ causeofdiarrrheain
continuestogrow w ComplicationsGuillian nBarre,reactivearthritis
CampyBacis developedcountries
Stool:PMN,RBCs
selectiveforthis!!
Antibioticassociateddiaarrhea(Dysentery510dayysafterantibioticcourse Normalflorain~55%ofhealthypeople.Canget
Enterotoxin(GIupset)andcytotoxin(killsmmucosalcells)leadto
G+anaerobicspo ore wateryorbloodyw/abd dominalcramps,leukocytoosis,fever)whichcanfurtheer nosocomially(buttcommunityacquiredisbe ecomingmore
disruptionofepitthelialcytoskeleton,lossooftightjunctions,
formingrod. developintopseudomem mbranouscolitis(colonis coatedw/plaquesoffibrin
n, commonfluoroq quinoloneresistantstrainw
w/toxin
cytokinerelease,andinflammation.
deadepithelialcells,mu
ucus,andinflammatorycellls).Seeneutrophilserupting production).Riskfactorsadvancedage,ho ospitalization,
ToxinA:causescellroundingandinterruptsstightjunctions
Dx:demonstrate fromcrypts. estinalflora
antibiotictx.Antibioticsdisruptnormalinte
alterspermeabilitty/secretion
toxininptfecal Dx:findcytotoxininsto
ool,cangrowonselectivemmedia andeitherpermitovergrowthbyresistantorganismsor
ToxinB:cytotoxicc(altersnormalintestinalfflora)
specimen Tx:discontinueantibiotiicimplicatedinproblem,trreatAADw/vancomycinor makepatientmorresusceptibletoacquisitionfrom
Binarytoxingene
esmarkersofhypervirule ence.
metronidazole,relapsesscommonduetopersistennceofresistantspores. environment.
G+rod,nonmotiile
Sporeforming, WaterydiarrheaN/D/painw/outvomitinggorfever
Anaerobic
Noinvasion Somestrainscaussenecrotizingenterocolitisspigbowelofcolon/ileeum
Doublezone R:Ubiquitouusinsoil
EnterotoxinintracellularCa,altersmembbranepermeability.Losso
ofcellularfluid, Gasgangrene
hemolysisonbloo
od T:Oralfecal
macromolecules
agar.
Mucinase:burrow wsintomucouslayerofsto
omach,residesthereattacchedtogutepithelium. Tx:Prostacycline, clindamycin,broadspectrrum
H2,CO2gas+
Adhesins(BabA) adheretosurfaceoffoveeolarmucuscells.Notinfo ociofintestinalmetaplasiaa. Mosthaveasxgasstritisbutareatriskofd
developingPUD(1020%develop)
Enhancesbindinggtorbcsw/Bag. andgastricCa
Urease:makesam mmonia+CO2fromurea((buffersgasricacidnearby)) Gastritis:anntrum(mostcommonhigghacid,highriskofduoden nalulcer), Notsureofttransmission
Expresstoxins(CaagAregulatesVacAcause escellinjury,damagesgasstrictissue,permeabilityyof pangastritiss(leadstomultifocalatrop
phy).Earlyseeerythematoous routeseemmtoacquirein
epitheliumtoureea) mucosa.Laater,coarse/thickenedrugaalfolds,evennodular.Latest childhoodan ndhaveit
Gnegcurvedrod.
Causeelaborationofphospholipasesthatd damagesurfaceepithelialccells(proteases, atrophy.MMicroscopic(biopsy)seeo organismsONfoveolarsurffaceand ecades.
persistforde
phospholipasesb breakdowngastricmucus) neckcellMU UCUS.Canbeseenw/H/EE,Giemsa,silverstains.Neeutrophils
Flagellaallowmo
otility
Doesntinvadetissues,butinducesaninten nseinflammatoryandimm muneresponse(IL1/6/8, (epithelial)aandplasmacells(laminap
propria).lymphocytesand
inmucus.
TNF) aggregregattesw/germinalcenters(inducedMALT).Noninvasivvetest
ImmunogeniccanattractB/Tcellsandleaadtogranulomas. detection=ammoniuminbreath,baccteriainfeces,absinserum m
Plateletactivatinggfactorcancauseocclusio
onofsurfacecapillaries Weirdfact: peoplew/duodenalulceronlyhaveHpyloriintheirr
Hpyloritakesadvvantageofmucuslayerthaatcoversstomachliningfightacidviaureaseenzym me stomachsperhapslinkedtoacidproduction?
convertsabundan ntureatobicarb+ammon nia.Itlivesinmucusliningofstomachwherebodys *1causeoffduodenalulcers
naturaldefensesdontreachuntileventuallytheycauseanulcer. #2causeoffpepticulcers(behindNSAAIDs)
mammals,food
Birds,fish,m
Majorcauseofstiillbirth,spontaneousaborttions.
LLOhemolysin
G+rod Primaryinfection sxin1wkN/D/pain/myaalgia Wedefenda againstthem
AcAprotein
Catalase+ Disseminatedm monthslaterconstitutionaalsx,meningitis. w/CMIhighriskif
3humanpathoge enicstrains4bmostcommon(causesfoodborneliisterosis)
Betahemolytic Intracellularwithinnmononuclearphagocyteesandepithelial,othernoon immunocom mp,young,old
SpreadissimilarttogroupBstrep
professionalcellss.EntersviainternalineescapesphagosomeviaLLO
Horizontaltransfeerfromcelltocellmeansttheyarentexposedtoimm munesystem
Dx:Gramstain hemolysinrepl icatesincytoplasmuseesAcAtohaveactintoprop pellikea Tx:Amp/Gen ntfor
Cancauseplacenntatoinfectfetus,caninfecctfetusinvaginalcanal
cometw/theirtaillhorizontallythroughmem mbranes. fulminant,alsosensitiveto
prostacycline e,TMX/SMX
BugsList,continued
TCP(toxincoreggulatedpili)adhesion:
Bundleformingpili,requiredforadh herencetointestinalepitheelium
GRod,highlymootile Choleraseverew watery(ricewatermucu usflecks)diarrheaduetoin
ngestion
Vibriocholera Encodedonpathogenicityislandonafilamentousbacteriophaage.
ofORGANISMnottatoxin.Littledamagetointestinalmucosaalleffeectsdue
ReceptorforCtxphage(encodescho oleratoxin)#percellcan
namplifyinvivo
Fermentsglucose ebut totoxinandresulttingfluidloss/electrolyteimbalance. Oralfecalsp
pread
ABsubunitprote einexotoxin:typeIIsecretion(holotoxinisformedinnperiplasm)
NOTlactose DOESNOTINVAD DE.NOhistologicchange.
B(binding))bindsGMgangliosideatbrushborderofSIepithe elialcells,facilitatesAentry.
Mortalityduetoddehydration(>60%ifuntx).Overallgutaborptionisin ntact ontaminated
Reservoir:co
A(active)isADPribosyltranferase: ADPribosylates/inactivatesguaninentprotein
Flatyellowcolonies Tx:fluids/electrolyytes water/food.Needto
(regulatesconversionofadenylatecyyclasefromactiveinactiveform)locksproteinin nto
onTCBSagar ingest~10^88cfu.
activeGTPboundstate.Resultisperrsistentadenylatecyclaseactivation,elevatedcAMP.
Prevention:improovesanitation.Vaccinesexxistbutdontprovidelongterm
OpensCFTRchannel(hypersecretew water/Cl,blockNa+absorpttion)leadstowatery
Oxidase+ immunity
Notepertussis,diphtheria
diarrhea.N ahavesamekindoftoxin!
Toxinproducedaatmucosalsurface,bindsG GM,istransportedintointeestinalepithelialcells
Vibrioparahaemolyticcus ParacholeraWWaterydiarrhea.Relativelyymildcomparedtocholeraa.
Gcommashaped
Bowelinflammatioon.
rods Shellfish,raw
wfish(25%of
molyticcytotoxin
Enterotoxin,hem Onset24hrs,lastss3days
Motile foodpoisoniinginJapan)

Halophilic(saltlo
oving)
Usuallyselfresolvvingcanusetetracycline,,ciprofloxacin
Cancausedysenteryliked diarrhea.AffectsRLQareaa(ileum,appendix,rightcoolon).EnterthroughMcells
Gramnegcoccob bacilli Yops(yersiniaoutermembraneprotein)dissruptscellularfx, Canspreadsystemiccally.
Yersiniaenterocoliticaa msoflaminapropriaandPeyerpatches,drainttomesentericlymphnodees.
Oxidase,Catalasse+, cytotoxic. riskinhemochrom matosispts.
Bowelthickwall,mucossalbleeding,ulcersenlarggedPeyerpatches.MESEN NTERICLYMPHADENITISW W
glucosefermenting Virulencefactore
expressionregulatedbyCaa++,temp. R:Worldwideconttaminated
/NECROTIZINGGRANULOMAS.Mimicsacuteappenndicitis,Crohns.
RequiresFefor Canparalyzephagocyticabilityofcell food,
Canhavepolyarthriticsynndrome1monthafteriniti alinfection(resolves36m months).Erythema
growth,difficulttto T:fecaloral.Highestratesin
nodosum(nodulesonlegss,resolvesin1month)
isolate Penetratesilealm
mucosa,multipliesinPeyerrpatches/regional European/Scandinav viancountries

Bipolarstaining lymphnodes.Bacteremiarare,usuallyseen nw/Feoverload (lowestinUS/UK)
Tx:notusuallyrequired.SSevereusedoxyclyclineaandaminogly;coside,bactrim,orfluoroquinolone
Baciluscereus Associatedw/ricethhatiscooked
G+sporulatingro
od Heatstableemettictoxinthattriggersseverrevomitinganddiarrhea Foodpoisoning:VVOMITING,diarrhea andthenkeptwarmspores
Motile Enterotoxins Onsetin16hourss,Usually<24hrduration germinateintherice
eand
vegetativecellsprod
ducethetoxin
Staphylococcusaureus Foodpoisoning:VVomiting,diarrhea(cantrigggerotherthingsliketoxic R:humanskinconttaminated
SomestrainsproduceheatstableSuperAgenterotoxins
shockifgetintob lood) foodpreparercancaauseit.
Superagtooxinsextracellular,oversttimulateimmunesystembyybindingMHCII/CD4and
Onsetin24hourss, Infoodsnotkeptsuffficiently
forceassocciation.Dontneedtobep
processedbyagpresenting
gcells,actaspolyclonalTccell
Usuallyafter<24hhrduration warmorcoldespeciallyeggs,
stimulatorss
FordxwanttocculturetheingestedFOODnotthestool! custard,mayo
Clostridiumbotulinum
m
Nausea,vomiting,,dizziness,cranial
G+rod,sporeforrming PotentneurotoxininhibitsAchreleaseatm
myoneuraljunctioncausesflaccidmmparalysis Endosporesinsoil
palsy,doublevisioon(mydriasis).
Anaerobic Foodpoisoningfrromingestionofpreformeedtoxin Cannedfoods,honey y
Oftenininfants

HepatitisA NOcarrierstatenevergoeschronic,but223relapsescanoccur. T:Fecaloral
AntiHAVIgM=acctiveinfection.
Picornavirus,Nakked, 3wkincubation,aacuteonset.LOWFATALITTY enters,prisons,
Occursindaycarece
AntiHAVIgG=re ecoveryfrominfectionorvaccination(protective)
+ssRNA Sx:fever,jaundicee,nausea,anorexia.1%go
otofulminanthepatits. travelerstodevelopingcountries,

StableatlowpH, malehomosexuals(a anal
Replicatesinente ericmucosaliverviremiia/infiltrationoflymphoidcellsnecrosis/proliferattion
inactivatedbybo
oiling Tx:supportivecarre intercourse)
ofKupffercells.A
Amountofnecrosiscorrelaatesw/diseaseseverity.
eimmunization
Px:passive/active Shellfish

Canhaveacarrierrstate.Chronicin10%ofiimmunocompetentpts
Serumsicknessprrodrome(510%)vasculittis(PAN),polyarthritis, T:parenteral,sexual,vertical
HepatitisB Hepadnavirus,
Daneparticles membranousGN. (pregnancy90%risskof
enveloped,circular
Cansurvive 426wkincubatioon transmissionduringdelivery,
dsDNAw/gaps
extreme incidenceofheepatocellularcarcinoma od
breastfeeding),bloo
(smallestDNAvirrus)
conditions Sx:fever,jaundicee,serumsickness,arthritis,,anorexia,nausea,RUQ transfusions.Presentinallbody

outsidethe pain.Hepatocyte damagesecondarytoTcellresponse.Hepatocytes fluidsEXCEPTstool.
Coreprotein
body havegroundglasssappearance
w/HBcAg
Thereisavaccine
Incubationtakes4426wks.

HepatitisC Canhaveacarrierrstate(chronicin70%)
T:parenteral,sexual,blood
Sx:mildhepatitis((jaundiceNOTcommon).
transfusion
Assocw/posttranssfusionhepatitis,typeIMP PGN,alcoholexcess,PCT,

Flavivirus,envelo
oped, NovaccineE2enveelopeprotein
E2,NS5AhaveIFN
Nactivity riskofhepatocelluularcarcinoma.IntermitteentlyhighALT
+strandssRNA isvaccinetarget(butthighly

variablemakesvacccine
Dx:AntiHBCabs, RNAtesttoconfirm
developmentdifficult)
Tx:IFNa,ribivirin,,livertransplant
BugsList,continued
Circular,ssRNA, UsesHBsAgasco oatproteintoinfect Canhaveacarrierrstate.Chronicstatelessllikelyw/coinfectionthan
Hepatitis
surroundedbyde elta superinfection T:parenteral,sexual
D
ag. Disadudbyitse
elf,butwithBitsprettybaad RequiresHBsAgtooreplicate(sohastohappenw/orafteranHBVinfecction)

orchronicstate.
Nocarrierstateo
40dayincubation n.Infectionoftensubcliniccal.Ifsxonlycausesacuttedisease,Fulminanthepaatitismaydevelopinpregnnantwomen(20%mortalittyinpregnantwomen)
T:Fecaloral (waterborne)
Hepatitis Sx:24wksbeforreresolution.
+strandRNA,nakked
E Happensinddeveloping
HEVRNA,virionsinstoolandliverbeforesxxALT/AST,Sx,IgMIggG countries
DxviaIgMabs.

Causesvomiting,wateerydiarrhea,fever,dehydraationinchildren.Nofecallwbcsor
Virusisingested,capsuleaidsinsurvivalofstomachacid. Oneofmo ostcommoncausesofserio ousdiarrhea
rbcs.Prodrome28daays,mostlyaffectsduodennum,jejunum(stomach,LB B,SB)
dsRNA inchildren
n.Ubiquitousworldwide,o occursyear
Asxinadults.
Detectvia Multipliesinmatureepithelialcellsattipso
ofvilliinsmallintestine round.955%ofchildrenaffectedbya age5,most
Rotavirus
immunoassayNO
OT causeslysisof cellsleavingimmaturecelllsthatdontabsorbas age624mmo
*1causeseverediarrh
hea(death)inchildrennoowvaccine.
culture wellloseelecttrolytes,reducedreabsorptionofwater T:Oralfeccallotsofvirusshedinfe
eces.

diarrhea/dehydraation. ROTAZYMEtestinfecesestablishesdx
Dx:immunoassayofsttoolforvirus
Diarrheaw/N/V((outbreaksofgastroenterittisfromcommonsource) MOSTCOMMONCAUSEO OFADULTGASTROENTERITTIS Gastroentteritisoutbreaksfrominfecctedfood
Calicivirus
2448hrincubation,1260hrduration.Selflimiting,Effectsinsmalliintestine(seelymphocytessinLP+SE,SEvacuoles,brrushborderloss,spruelikeevillus handler
(Norwalk
ssRNA blunting) #1causeoofoutbreaksofsecretoryd diarrhea
virus,
Stool:Norbcsorwbcs worldwidee,alsocommonlycausesporadic
noroviruses)
Histo:LymphocyttesinLP+SE,SEvacuoles,,bruishborderloss,spruelikevillusblunting infections.Stomach,smallbowel.
Mumps Inhaledlungs replicatesinTlymphocyytessalivaryductcells
mmonly
Inhaled,com
Ms,lymphocytess,plasmacellsaccumulatee
ssRNA pediatric
Hemagglutin,neu
uraminidase,hemolysin
Paramyxovirusfaamily
Sxflulike.3wkpprodromeparotidglandinflammation.Parotitis,
MMRvaccine
constitutionalsx. Alsoassociatedw/meninggitis,pancreatitis,ovary,orchitis.

Giardialamblia Cysts=infectivesstage(persistinenvironme
entalwater,onfood, Waterydiarrhea,flatulence,steatorrhea waterborne(mountainsttreams,
Primarilyw
Flagellatedprotozoan
fomites) Canblockabsorptioninsmallintestine(duodenuumhasbluntedvilli, beaverdams)
thatparasitizesG
GI
Developintotropphozoitesonceingested,caandivideandmultiply lymphocytes/plasmaccellsandhastheseorganism msadheredtotheepitheliium) ThosewithhoutIgAorlowIl6.havesevere
tractofhuman,oother
Developbackinto ocystsincolon Stool:foulsmellingsteeatorrheaw/N/V/abdpainn,flatulence.Monocytes,ccysts. infections
animals
Lactasedefin2040% Smallinfectiousdose(cystresistanttostomach

Doesntinvademakeaproteinlikeatoxin n(giardin)thatcauses acids)
Trichromestain
waterydiarrhea.Bothformsinfeces. Tx:metronidazole,treaatwaterw/tinctureofiodiine. Dximmu unofluorescentstainforcyystsinstool
Liquefactiveflaskulcers:Trophozoitesburrow formflaskulcersincecum m+LB.Can
havelungmigrationph hase(40%gotoliver,rarellymigratetolung)
Colonizecoloniceepithelium. Grossly:seeulcers(normaltissuebetweenulcers rsgreatestamountintheececum.
Entamoebahistolyticaa Ingestcystsinfoo
od/water.Excystationinsmmallintestine, Complications:stricturres(ifcircumferential),liveerabscess(solitaryormulttiple,looks
trophozoitesmigratetolargeintestine likeanchovypaste inflammation/shaggyfibriinlining+centralhemorrh hage,can Oralfecaltransmissionofcysts.
Invadeintestinalmucosa,cangosystemicaandinfectlungs,liver causelungabscess)
n
(rightlobe),brain
WorldwideRiskinmalehomose exuals,
Spreadwhenquaadranucleatecystissecrettedinfeces
travelers,recentimmigrants,instituttionalized
Movesviapseudo opodia.Cystsresistanttogastricacid
LectinbindsCHOonrbcs,attachestoepitthelium.

Amebaphorech hannelformingprotein hostcelllysis
Tx:metronidazole,trytopreventbyboilingwateer,goodsanitation
Bloodinstoolindicatesactivedisease.
Cryptosporidium
parvum Oocystsingested Survivesharshcoonditions(bleach),freezinggkills. Spts(300%
Expecttoseeinchildren<5yrs,AIDS
Sporozoitesareaactive Ingestedoocystsareactivatedbygastricaccid. immuneinnUS)highlyinfectious
Cryptosporidiosis:Watterynonbloodydiarrhea.VVillousatrophy,cryptenlaargementin
form Sporozoitesarereleased(25umbasophiliccspherules)adhereto Foundinw
water,food,soilworldwide e.
jejunum
Obligateintracellular e,mostlyterminalileum,Rcolonengulfedin
epithelialsurface
Malabsorptionmayocccurifpersistent.BiliarytrractinvolvementinAIDS
parasite(lifecycle
ein vacuolesinmicroovili.Nomucosalchangesunlessmassive,persistent Dx:immunnofluorescentstaindetectsoocystsin
infectedenterocyyte. infectionvilousblunting,atrophy,inflammmation. stool

Importantmeedia/teststoconssiderwhendxinffectiousGIdisease:
MacConkey:Selective(onlyallowsGtogrrow),Differential(LactosefermentermakesredcoloniesexEcoli,otherGlactosefermenters)
HektoenEntericc:Differential(onlyGandnonfastidiousgrow),Diffe erential(lactose/sucrosefeermentersmakebrightoraangecolonies,nonlactose//sucrosefermentersaregrreen/bluegreen,H2Sprod ducersmakeblackprecipitate)
CNA(ColistinNaalidixicacid):SelectiveMeddia(G+onlygrowonit)
Campybloodaggar(CampyBAP):Selective eisolatescampylobacterffromfecalspecimens
TSI(TripleSugarr):
o Butt(lactoose)/Slant(glucose)
o Kalkalinee(nonfermenter),Aacid(ffermenter),GGas.
o Ex:Ecoli==A/AG.Salmonellatyphi=
=K/A+G.Shigella=K/A.Psseudomonas=K/K.
MotilityAgar:Sttabsemisolidagarincubbate24hrs.Ifmotile,orgw
willdiffuseintomediuman ndcauseturbidity.Ifmotileseeconeofturbidity.Nonmotileorgonlygrow alongstabline.
Oxidasetest:Eccoliisoxidasenegnocolo
orchange.+testhascolonniesturnpurpleblack.
Indoletest:Deteectsifbacteriacausesredu
uctivedeaminationoftrypttophan,producinganindo etopinkin30seconds.ttesthasnocolorchange. Ecoliispositiveforthistest,klebsiellaisnegative.
ole.+testhascolorchange

Osmoticdiarrhea: Motilityabnormalities Watery/blo oodystool
Definition:in ntraluminalosmolalitylitttle/nopassiveelectrolyteaabsorptioningut,cannotssustainosmotic Luminalflowdependsonpressuregradients. Generallylittleworkuprequiredunleessseverelyill,bloodydiarrrhea(ifnot
gradient.3.mLLwaterretainedinlumenfforeachadditionalmOsm.stool(water)osmoticggap.290292 Directionandspeeddueetostrengthandfrequenccyof infection,cconsiderIBD,bowelischem miainelderly),epidemicsettinghospital
(Na+K)=gap>500mOsm/kg.Unabsorbedo osmolswatervolume eoverwhelmsthecolon contractionsnupstream,resistancedownstream. setting,anttibioticusehx,seriouscommorbiddisease.
Causes:Laxativees(Mg,SO4,PO4,PEG),No onabsorbablesweeteners(mannitol,sorbitol),CHOmaldigestion flowtransittime(exIBS,diabetic Chronic
(intraluminald disaccharidasedeficiency,pancreaticexocrinedeficie ency),Malabsorption(murral)tolesser neuropathy,scleroderm ma,bacterialovergrowth,bbile Maypresen ntasrecurrentacute.
extentCeliacssprue,othersmallboweld diseases,Fasting/stoppingo offendingagent/stopsd diarrhea aciddeconjugation,thyrrotoxicosis) Includesfunctional(IBS),meds(surreeptitiouslaxativeuse),
Secretorydiarrhea: Smallbowel/rtcolonsseeveryhighvolume,wateery malabsorpttion/maldigestion(celiacsprue,disaccharidasedeficiencies,
Definition:Netssecretionofwater(moreccommonthanosmoticdiarrrhea).Disruptedmucosalabsorptionand stoolsfromsecretion/absorptionoverwhelm ming chronicpan ncreatitis,IBD),previousGGI/biliarytractsurgery,systtemicdisease
secretionseccondarytodisorderedelectrolytetransport.DrivingforcesusuallyCl/bicarbsecretion, colonorlargevolume,faattygreasy,malodorous (HIV,DM,tthyrotoxicosis,malignanciees)
inhibitedNaabssorption.Stoolwaterosmoticgapnot.290292(Na+K)=gap<30mOsm/kgg.Unaffectedby Largebowel(especiallyd distal)smallvolume,muucusy LargerDdxthanacutediarrheafocu usonprobabilities
fasting. bloodystoolurgency,tenesmusfrom o IBS:If<50,noredflags,fitROM
ME3criteria
Bileacidsifmalabsorbed,reachcolon,stimulateH2OsecretionviaacAMPsecretion.Excee edscolon distensibilityofinflamed
dstiffwall o IBDendoscopy,biopsies
absorptivecapaacitydiarrhea. Acutte o Disacccharidasedeficiency:dod dietaryexclusion,H2breathtestafter
Steatorrhea:OH HFFAhavelaxativeeffectooncolon.Malabsorption(T TGsdigestedtoFA,inhibitingcolonicwater Includesmostinfectionss(travel,camping, ingesstingsuspectedsugar
absorptionseecretorydiarrhea).Maldiggestion(luminaldefect)likepancreaticinsufficiencyyTGsnot hospitalization,epidemic),assocw/meds(antibiottics, o MalaabsorptiontestHb,PT,Caa,stoolfat
digested,theoreeticallylessdiarrheaalthou ughstoolbulky/soft. antiHTNsBblockers,H H2RBs,PPI,chemotx);Dietaary o utaminase,endomysialab,smallbowel
Celiaacsprue:testIgA,transglu
Alsocausedbyn noninvasiveentericinfecttions(bacterialcoleratoxxin,Cdifftoxin,ETEC,Cjejuni,rotovirus, (dairyproducts,nonsuggarsweeteners,rarefood biopsy
norovirus,aden novirus) allergy,stres o Surreeptitiouslaxativeabuse:teeststoolforlaxatives
o Infecctions:Lookforgiardia,C.jjejuni,HIV,etc


Radiology
Contrastagents:
Radioopaquematerial
administeeredtosee
structuress/pathologicprocesses
thatwouldnotbeseenotherwise
Usefulones:bariumsulfateinGI
tract,Iodinecompoundsin
vessels,CO2invessels/GItract,
naturallyoccurringairinGItract
Intestinalmotilitty
Evaluated dbyfluoroscopy:
intestinalobstruction,paralytic
ileus(lackkofperistalticactivity),
intussusceeptions,
Pneumop peritoneum
MechanicalObstructionofSmallbowel
Smallbow weldilated>3cmw/gas
(swalloweedair)andfluid(excretedb by
digestiveglands).Formsmultipleaiirfluid
levels.Plaainabdominalfilms(erectand
supinevieew)toconfirmthedx
Multipleaairfluidlevels,stepladdering
(intestinalcontentsmovetowardre
fluidpushhedupoverloopsdifferent
levelsind
differentareas)
Linitis
plastica:diffusenarrowingin
proximalstomacch,diffuse
infiltrationoflym
mphomainwallof
stomach.Nomo otionon idio
fluoroscopy(perristalsisimpeded)
SupinevsUprightabdominalXray: NormalMucosal AcuteAbdominalSeeries
Supine:airinboddyofstomach,transverseccolon(anteriorstructures) folds: Supineabdom men(KUB/flatplate)
Prone:airinfunddisofstomach,rectum,asccending/descendingcolon Valvulae Uprightabdoomen:detectsairfluidleveelsandfreeintraperitonealairhorizontalbeamparalleltoflooris
Upright:airinfun
ndus conniventeso of used.Ptneeddstobeinuprightposition natleast10minpriortoraadiograph
Decubitus:Rtside eairinrtcolon/duodenu um;Leftsideairinleft smallintestin
ne Chestxray:ddetectsfreeintraperitoneaalair/chestpathology
colon/stomach Haustraof LLDecubitousabdoomensubstitutesuprightviewindebilitatedptpttneedstomaintainposition10min
ReadingtheXRay:ABC CDApproach: colon
Air(pattern,freeair) GastricRugaee
Bone(anychange eshappeningaffectingptssx?) ofstomach
Calcification(uretteral,gallbladder20%calcified,pancreatic?)
Density(anyabno ormaldensity,softtissuemmasses?Dosize/configof
normalorganslookok?
SmallbowelcanbeexxtensionofupperGIexamfollowbariumthrough
bowelw/serialfilms.Ennteroclysiscanalsobedon ne(canidentifybetter
mucosaldetail).
MechanicalOb bstructionofLargeBowel Paralytic(adynamicileus):T
P Thebowel Penumoperritoneum:Freegasinperittonealcavity Contraststudies:
Distende edcolonfromcolontoleve elofobstruction lu
umenispatent,butfunctio onal Com monlyduetoperforationofGItract(pepticulcer), Bariumorwater
w/airanndfluidinside defect.propulsiongen
d neralizedor Folloowingsurgicalprocedure(laparotomy) solubleagentsusedto
Incompe etentileocecalvalveletsgaasbackwardinto lo
ocalized Xrayysigns:onerectabdominaal/chestfilmacurvilinearr(small fillthelum
men
smallboowel Largeandsmallbow weldilation, amouunt)orcrescent(moderateeamount)oflowdensityggas indirectlyyhelpevaluate
Dilatedccolonindistaldescendingandsigmoid occasionallystomach hdilated area betweenopacityofdomeeofdiaphragmandliveron nthe themuco osa.
Commonlyduetocancer,volvuluss(midgutinchildren, also righttmostreliablesignforidentifyingthiscondition.W
Withno Evaluateforbarium
ectum, cecalinadults,sigmoidinelderly) Commonlydueto furthhergasorotherconditio onthefreeairwillbeabsorbed extending goutoflumen
Uprightviewshowsmultipleairflu uidlevels(largerthan intraabdominalinflam mmation, in7110daysormuchfaster(12days)inchildren (ulceratin ng,
thoseseeeninsmallbowelobstructtion) postsurgicalorposttrraumatic ExsseeCurvilinearareabetweeenrtdiaphragmandliverr inflamma atoryprocess)
reaction,spineinjuryy
UpperGIExamination
Bariumenema:Bariumcoats
mucosa,followe edbyCO2.
Coatingofmuco osaand
distendedw/gas.Appendixis
filledw/barium also
Boerhaav
Gastriculcersbenignulcer(u ulcer
Achalasia: es Neoplasmsinstomachwall
projeectsbeyondgastriclumen,,
Disstended syndrrome MalloryWeiss(nnontransmural silhouettetumo ormasslooks
sharp pmargin,roundbariumdo ot
esoophagusw/distal (transmur tearcausedbyseevere likeafillingdefecctextending
view
wedenface,edematoushalo
Esophageal biirdsbeaksign al retching/vomitinng)Othercauses intobariumcolum mn.Irregular
aroundulcerinacutestage,gaastric
carcinoma ofttenseefoul perfooratio ofesophagealruuptures:, fillinginstomach isspace
foldssradiateoutlikespokesoff
odors,vomitingof nseeen iatrogenictraumma(8590%of occupyingcomm monlysee
wheeelinsubacuteorchronicsttage,
esoophageal w/vo omitin cases),foreignboodytrauma GISTs(leiomyoma as,
perfoorationleadstolargeamounts
conntents g, adenocarcinoma,,lymphoma)
offreeeintraperitonealair).
bulimmia),
Malabsorption:willsee Crohnsdise ease Complication ns Diverticulitis:com
mplicationof
changeinappearaanceof unknownetiology, obstruction,ffistulas, Diverticulosis diverticulosis,inflaammatory
bariumcolumn transmural,can abscess.Areasof multiple process.Causesp perforationof
segmentation,flocculation, affectanypaartof narrowingseeparatedby diverticula diverticulum.Inflaammatory
dilution,separatio
onof alimentarytract, areasofmorenormal processusuallyloccalizedand
loops.Sprueexin
npicture mostlyaffeccts bowel.Separationof formspericolicabscess.Can
terminalileuum, loops,fistulas developfistulastoovagina,
proximalcolon,may bladder,etc.Extraavasation
Duoodenalulcerstypically affectduode enum. Diverticulaa fromlumenseen,abscess
locaatedinbulb.Maybeassocc Cobblestone e mucosaprrotrudes cavityw/bariumseenin
w/ggastriculcers.Mayperforaate, appearance(edema outofbowwel picture.CanalsouseCT
mosstcommoncauseofnon w/crisscrossed lumenthroougha evaluation(seeinfflammatory
opathicpneumoperitoneum m. ulcers).Skip
pareasof weakpointntinmm processinthemessentery
Mayypancreatitis normalbowel. layer. w/aircollections)
 Polyposis:canidentifyw/singleconttrastbarium
TumorsofGItracct: enemasseemultiplesmallfillingde
efectsfrom
UlcerativeColitis: polyps(heereditarypolyposissyndromme).Polyps
Appendicitis:CTisusefulst
A tudy mostcommonlyfoundinrectosigmo oidalregion
Unknownetiologymucosalinflam mmationandulcerationinlaarge Generalsignfilllingdefectmassreplacesbarium.
Irregulargraydensityy
bowel.Allwaysinvolvestherectum..Earlywidespread
representsinflammatory
fuzzy/serrratedulceration.Laterigid
dtubeappearance(Lead CommonsignsoffUpperGItumorbybarium mmeal
changeinRLQinareaaof
pipe)chronicscarringcausesnarrowing,lackofperistaltic mass,constrictioon,ulcerationwhenmassggrows
theappendix.Maysee
activity,lo
ossofhaustra,narrowing,smoothsurfaceofdistal beyondbloodsu pply.
stoneinappendix
colon/rectum.Complicationstoxicmegacolon,carcinoma.Late
(fecolith).
stagecanshowmarkednarrowing,abnormalsmoothnessw/loss CommonsignsoffLowerGItumorbybarium menema

ofhaustraations. polypoidmassleesion,annularconstriction

Hepato
obiliaryevaluation: Cholecystitis:UsseUSEchogenicfoci
Coloncarcinomaa:abrupt Pancreasevaluation
Standardradiographsmo
S ostvalueinevaluatingcalcifiedgallbladderstones(20
0%) (gallstones),thickkenedgallbladder
narrowingoflummenascending Imagingevaluationplainfilmsentinelloop p,calcifications
Nuclearmed:lookateithe
N rKupfercellsorhepatocyttes,functionalevaluation wall,pericholecyysticfluidmaybe
colon,primarynneoplasm (chronic);ultrasoun nd(enlargements,cysts),CT T(fluid
US:fast,inexpensive,fairly
U yaccurate,goodforGB,somefunctionalevaluation theMOSTSENSITIVESTU
UDY difficulttodiscrim
minateacuteand
lookslikeanAp
pplecore collections,infiltrationoffat,density,losso
oftissue
forgallstoneandgallbladd
f er.Appearround,echogenicseeacousticshadowiing chronicdisease
planes,calcificationnschronic),MRI(fluidcollections,
Dilatedcommonbileduct:causes
edema)
includestone(m mostcommon),
Sentinelloop:dilateedduodenalcloopcau usedby
carcinoma.DoaalongitudinalUS
irritationofretropeeritonealportionoftheduo odenum.
throughliverhiluumseetypical
Wideningofloopcaausedbyedemaorpseudo ocyst.
doublechannelssigndilatedcommon
bileductanteriorrtoportalvein.Duct
usuallysmallerthhanvein.USbest
initialimagingmoodalitytoevaluatefor
CTcolonographyy: dilationofbiliaryytree.
CT:moreexpensive,verya
C accurate,canevaluateforccontrastenhancement,ion nizingradiation
Minimallyinvasiive
MRI:mostexpensive,nora
M adiation,canusecontrastaagentsspecificallyforliverrreallygoodforhemangiioma
examination,reqquiressame
ofliver.Detectsironaccum
o mulationsinliver(hemochromatosis)futurevalueb byusingironcontrastaggents
prepascolonosccopy.Sensitive
HIDAimaging:radionuclide
H etargetedtohepatocytes. Nonfillingofthecommon nbileductorgallbladder
tosubcentimetterpolyps.
indicatesobstructiveproce ess
Substituteforen
ndoscopy.Still AcutepancreatitisC CT:seeedema(densityiinfatty
Sulphurcolloidscanliverm
S metastases:labeltheRESsyystem(usedlesstoday)
willrequireendo
oscopyif structures)andlosssoftissueplanesaroundth hepancreas.
Labeledrbcstudylookfo
L orareasofuptake(seeinh
heart,spleen,focalareainliverinthiscaseshowingga
abnormalityfouund. Fluidcollections(psseudocysts).Diffuseinflam
mmation
hemangioma)
h
Completedevalu uationif Phlegmon(maydevveloptopseudocystsasenzymes
Plainfilms:Gallstonescan
P beseen(inthe20%thatactuallyhaveCa++)Appeaarfaceted,denserimw/less
normal.Radiationrisks. breakdowntissuein ntheseareasofinflammation).
densecenter.Separatedfr
d romrenalcalculiorcostocchondralbydifferentpositiions,morefilms.