PathGILiverBiliaryExocrinePancreas

CONGENITALDISEASESOFTHEESOPHAGUS

TracheoesophagealFistula

Esophagushasbothatresia(blindpouch)andfistula(connectiontosomethingelse)
Atresia Patientshavethetracheaandesophagusconnected
o Patientsswallowfoodintotheirlungs=aspirationpneumonia
Fistula
o CoughingandCyanosisduringfeeding
o Amnioticfluidcannotbeswallowed,causespolyhydramnios
Mostcommon
Mustbesurgicallycorrected,whichiseasilydone.
presentationof o Mostcommon=atresiaofupperesophagusandfistulaofloweresophagustotrachea
atresia/fistula
EsophagealWebs

Weblikeprojectionsofesophagealmucosaintothelumen
Foodgetsstuckinwebs,presentingwithdysphagiaandbadbreath
Associatedwith
o PlummerVinsonSyndrome=webs,irondeficiencyanemia,women,Riskfor
sqaumouscellcarcinoma
o SchacktziRing=websdownattheesophagealgastricjunction

Achalasia
Esophagus
o InabilitytorelaxtheLowerEsophagealSphincter(LES)
o Presentswithdysphagiaormegaesophagus(cantgetfoodintostomach)
BirdsBeak
o Diagnosedwithbariumswallowrevealingbirdsbeakesophagus
Stomach o CausedbydeathofganglioncellsintheLES
o Treatedwithstentingorsurgicalresection
Pylorus


HEMATEMESISANDBLEEDS

MalloryWeissTear

StomachLesionEsophagus o Associatedwithretchingorprolongedvomiting=bulimicsandalcoholics
o Arelongitudinaltears,usuallyatthegastroesophagealjunction
o Maycausehematemesis,butbleedingusuallyspontaneouslyheals
o Lesionsmaycompletelyhealovertime,ifretchingisdiscontinued


EsophagealVarices

o Patientswithliverfailuredevelopportocavalshunts(LeftGastricVeinEsophageal)
o Oneshunt=esophagealveinsgivingrisetodistending,tortuousveinsinesophagus
o Varicesarepronetoruptureproducingmassivehematemesisandmelena
o Surgicalemergency;thesewillnotspontaneouslystopontheirown
Candoaballoontamponadetotemporarilystopthebleeding

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Endoscopywithprotrudingdistendedveins(arrows) Sheets

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ESOPHAGITS(BigRobbins803,BabyRobbins412)
Esophagitis=inflammationoftheesophagealmucosa.Ithasmanycauses,butherewecoverthemost
commonthree:Reflux,Barretts,andInfectious/Chemical

RefluxEsophagitis,akaGERD,akaHeartburn

Definition
o RefluxorregurgitationofgastriccontentsthroughtheLEScausingcausticdamageto
theloweresophagus
Causes
o LESToneallowinggastriccontentstocomebackouttheinhole
CNSdepressants,Pregnancy,Obesity,Alcohol,andTobaccoallincidence
o PresenceofaslidinghiatalherniawithsubsequentdilationofLES
o Inadequateorslowingofgastricemptyingwithincreasedvolumeofstomach
Elongationofdermal
papillaeandbasalzone
o Actionofgastricjuicesiscriticaltothedevelopmentofmucosalinjury
hyperplasia Morphology
o Dependentonseverityandexposuretime(twoweeksversussevenyears)
o SimpleHyperemia(redness)maybetheonlyindicator
o InflammatoryInfiltrate=PMNs,Lymphocytes,and/orEosinophils Redstreaksarehyperemia.
o BasalZoneHyperplasia>20%ofepithelialthickness Endoscopicimage.

o ElongationofLaminaPropriaPapillae
Clinical
o Commonwithincreasedage(>40)thoughpossibleinchildrenthroughadulthood
MinorEosinophiliainthe
Esophagusisalmost o Severityofsymptomsseverityofdisease(lotsofburningwithoutlotsofchanges)
pathognomonicforReflux. o Mostcommoncomplaintisheartburn,diffuseburninginthecenterofthechest
LOTSofeosinophilsmeans
o Ifnottreated,theburningwillstopasmetaplasticchangescreateBarrettsEsophagus
EosinophilicEsophagitis

BarrettEsophagusthis,orcancer,willundoubtedlybeonyourTulaneexam,Shelf,andonStep1

Definition
o LongtermGERDresultsinaprotectivereplacementofdistalesophagealsqaumous
epitheliumbyametaplasticcolumnar,glandularepitheliumresemblingtheduodenum
Pathogenesis
o LongstandingacidicpHintheloweresophagusinducesmetaplasticdifferentiationof
pluripotentstemcellsintocolumnartypeepitheliumwithgobletcells
o AprotectiveprecancerouschangetodefendagainstacidicpH

Morphology
o Gross=circumferential,red,velvetymucosaatthegastroesophagealjunction
o Micro =columnarepitheliumwithglandulardifferentiationandgobletcells
=Dysplasiaisnotrequiredfordiagnosisbutiscriticalforprognosis
Clinical
o GERDlasts20yearsbeforeBarrettssetsin SalmonVelvetappearance
o Patientgoesfromsevereheartburntonopainspontaneously(progressiveoracute)onendoscopy
o Thisisprecancerouswith3040TIMESriskforadenocarcinoma
o TreatmentwithPPIscanpotentiallyreversebothdysplasiaandmetaplasia

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ColumnarEpithelium
withgobletcells=
Barretts
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InfectiousandChemicalEsophagitistheothers

Types
o Ingestionofmucosalirritants=alcohol,corrosiveacids/alkali(suicide),hotbeverages
o Infectionofanykindsuchasfungus(candida),bacteria,orvirus(Herpes,CMV)
o UremiafromRenalFailure
Morphology
o Dependentonetiology,BabyRobbinsbasicallysaysdontbotherwithspecifics
o Allshareacuteinflammation,superficialnecrosis/ulceration,andeventual
granulation/fibrosis
Candidaesophagitis.Thisisafungus
HerpesEsophagitis.Inthe
showingpseudohyphae,stained immunocompromisedindividual,
blackagainstagreenbackground. lookforCowdryTypeAandCowdry

Candidanormallylivesinthemouth; TypeB.Thereistypicallynuclear
youmusthaveinvasiontocallit moldingandinclusionsshowing
candidiasis.Usuallyoccursinthe perinuclearhalos.
immunocompromised.ItisanAIDS
definingdisease.
TUMORS(BigRobbins806,BabyRobbins413)

MalignantTumorsSqaumousCellCarcinoma

Definition
EtiologyandPathogenesis
SCCshowingKeratinPearls
(arrow)amidstdysplastic
mucosalepithelium
LungEsophagusTumor
Tumorgrowingontopof
lungs,fromthemid
esophagus,meansitmust
beSCC
o Dysplasticcarcinomaofthesqaumouscellsoftheesophagus
o Obviousimpactofvariousenvironmentalfactorscombinedwithgeneticpredisposition
o Chronicesophagitis,Alcohol,orTobaccocontributetorisk
o Mostcommonesophagealtumorworldwide
GERDBarrettsAdenocarcinomaequaltoormorecommoninUS
Morphology
o SimilardevelopmenttootherSCC,withcharacteristicbenigntransformationthrough
carcinomainsitu,andpresenceofkeratinpearls
o Appearasgraywhiteplaquesorelevations(unnoticedexceptonendoscopy)
o Locationoftumormayhelpidentify
SqaumousCellCarcinomacangrowanywhereintheesophagus
Adenocarcinomacangrowonlyinlowerthird
Ifitisinproximalesophagus,thenitmustbeSCC
Clinical
o Insidiousonsetwithwithoutearlysymptoms(earlydetectiononlywithendoscopy)
o Dysphagiaislate,ominoussign,usuallyindicatedbyachangefromsolidtoliquidfoods
o Earlydetection=positiveprognosiswithresection
o Latedetection=poorprognosisfromtumorinvasion
o HemorrhageandWeightLoss(tumorstealsnutrientsandcausesmalnutritionfrom
stenosis)arealsopossible.

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MalignantTumorsAdenocarcinoma

Definition
o Truemetaplasiaoftheesophagustogastricmucosawithsubsequentdysplasia;when
Barrettsturnstocancer
EtiologyandPrevention
o MostcommonesophagealtumorintheUS
o EssentiallythisiscausedbyBarrettsEsophagus
HighgradeDysplasia o Helicobactermaycontribute,buttheonlywaytogetglandulartissueintheesophagus
ismetaplasiaorlocalspreadofgastriccarcinoma
Morphology
o Locatedinthedistalesophagus
o Theyareflat,mucinproducingglandulartissueresemblingtheduodenum/stomach
o Degreeofanaplasiavarieseveninlocationsadjacenttoobviouslesions
Clinical
o Presentswithdysphagia,hemorrhage,andulceration,justlikeSCC
o Prognosisisverypooroncetheyreachthisstage
o Theyhaveanobviousclinicalcourse

Grossimageofesophageal 10yearsofheartburnwithouttreatmentforGERD
adenocarcinoma.Normal 25yearsofBarrettswithouttreatmentforGERD
mucosa(blue),gastgric
mucosa(red),
15yearsofadenocarcinomaleadingtotheirdeath
adenocarcinoma(yellow) o ProtonPumpInhibitorTherapypriortoadenocarcinomaformationiscurativeand
reversedmetaplasia/dysplasiabacktoesophagealmucosa

InitialsymptomsofGERDwhere Theburnbeginstospontaneously Metaplasiahasgivenwaytodysplasia.Youvegotcancer.
heartburniscontrolledbyPRNantiacids, disappearoverthecourseofyears.You Cancerousgrowthshowsnosignsorsymptomsuntilyoucant
followedbyOTCdrugs.Theburnmeans
feelbetterbutyouresophageal eat(dysphagia)orafistulaismadetoyourlungs(aspiration
youresophagusisnormal pneumonia).Youdiewithin5years(20%5yearsurvival)
510 epitheliumhasundergonemetaplasia
years 25 years 15years
Heartburn,AcidReflux,GERD BarrettsEsophagus Adenocarcinoma Death


ProtonPumpInhibitorsare ProtonPumpInhibitorsarecurative. Youarescrewed.Atthispointitstoo
preventativeofdisease.Getan Theyreversethemetaplasiaand late,asthesearenastyinvadersand

endoscopytotrackchanges holdoffdysplasia.Getendoscopyfor haveaverypoorprognosis,even
diagnosisandtotrackchanges withresection

ProgressionofGERDtoCarcinoma

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STOMACHSTART

CONGENITALSTOMACH(BigRobbins812,BabyRobbins415)

PancreaticHeterotopia=islandsofpancreasfoundwithinmucosaorthemuscle
Diaphragmatichernia
o CongenitalDefectinthediaphragm,allowingintestinesintomediastinum
o lungdevelopment(pulmonaryhypoplasia)ifsevere
PyloricStenosis
o Occursinmalesmorethanfemales
o Patientwillpresentwithnonbiliaryprojectilevomitingaftereating
o Lookforolivelikemassinthevignette
Thereisanovergrowthofmuscle,causingaphysicalobstruction
Myotomyiscurative,removingtheexcessmuscle
MenetriersDisease
o Thisisaproteinlosingenteropathythatisnotcongenitalbutdoesntfitanywhereelse
MenetriersDiseaseand
Ifpatientpresentswithedemaorascites,buthasnormalkidneysandliver,look
ZollingerEllisonbothhave
enlargedrugae,butdonot forthisdiseaseasanoptionchoice
looklikeeachotheratALL o Therewillbesignificantlyenlargedrugalfoldscausedbyaproliferationofmucouscells
inpresentation
Mucous=ParietalCell=AcidicContent=Digestion=Malabsorption
Mucous=ChiefCells=Pepsinogen=Digestion=Malabsorption
Mucouscell=Proliferation=riskforCancer
ZollingerEllison
o Agastrinsecretingtumorofthepancreas,causinganincreasedrugalfoldsize
Gastrinisthegrowthstimulatorandacidsecretionstimulatorfortheparietal
cells(differentiatingfromMenetriersDisease)
AcidicContentleadstorefractorygastricandduodenalulcers
Crosssectionshowingenlarged
Gastriniselevatedinthebloodatalltimes,anddoesnotsufferacidcontent
foldsofthemucosainZollinger feedbackastheGcellsdointheantrum
EllisonSyndrome
o Ifyouseeapatientwithaduodenalulcer(gnawingepigastricpainrelievedbyfood)and
H.Pyloriisnotanoption,pickZollingerEllison

GASTRITIS(BigRobbins812,BabyRobbins416)

Definition

Histologicdefinitionmeaninginflammationwithinthegastricmucosa
Canbeformanyreasons,andbeacute(rightnow)orchronic
Gastritiscanpresentasanerosion(superficiallesion)orulceration(deeplesion)

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AcuteGastritis=GastritiswithoutH.Pylori

Associatedwithmanycauses(NSAIDs,ASA,EtOH,Smoking,NGTubes,Uremia,Chemotherapy)
Mustbeafailureofmucosaldefense
o ParietalCellmass=acidproduction,causedbyGastrinorSensitivitytoGastrin
o Regurgitationofduodenalcontents=detergentdamage
o Ischemia=mucosallayernecrosis=noprotectivemucous
o NSAIDs=Cox=prostaglandins
Presenceofneutrophilsdefinesacuteinflammation
o Theremaybeerosionofmucosallayer
o Theremaybeulcerationofmucosallayer(seeacuteulceration)
o Theremaybehemorrhageintogastriclumen(hemorrhagicgastritis)
Presentationcanvaryfromasymptomatictoepigastricpain,nausea,vomiting,uptomassive
hematemesisandmelena(whichislifethreatening)

AcuteGastricUlceration=StressUlcersorSuperAcuteGastritis

Small(<1.0cm),focal,oftenmultipleerosionsorulcersofvaryingdepth
Representerosivegastritisfollowingasignificantstressor(burns,shock,sepsis,headtrauma)
o Splanchnicvasoconstriction(cellularhypoxia)andacademia(lowpH)injurescells
o NSAIDs,whenabundant,cansignificantlyimpairmucosaldefenses
Healindaystoweeksifunderlyingcauseisfixedandpatientsdontdiefirst
Foundinintensivecarepatients.IffromICP=Cushings,iffromTrauma=Curlings

normalmucosa(arrowheads)hemorrhagicmucosal
Multipletinystressulcers,highlightedby
Grossviewofpunctuateerosionsinan thedarkpigment(digestedblood)onan
disruption(arrow)
otherwiseunremarkablemucosa otherwisenormalmucosa

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ChronicGastritis=GastritiscausedbyH.Pylori

Definition
o ChronicMucosalInflammationthatmayleadtomucosalatrophy,intestinalmetaplasia,
dysplasia,andevencarcinomausuallywithouterosion
Pathogenesis
o TypeA:Autoimmunegastritis,FundicType
TypeAisAutoimmune AntibodiestargetandkilltheParietalCellsandelimateIntrinsicFactor
AutoantibodiesdirectedagainstH/KATPase,GastrinReceptor,IntrinsicFactor
TypeBiscausedbyaBug
Leadstochronicinflammation,Acid(infection),andPerniciousAnemia
o TypeB:H.PyloriInfection,AntralType
Itisflagellatedandmotileallowingittoswimthroughmucouslayer
Possessesurease,cuttingupureaandsecretingabufferagainstlumenacid
Yieldsapositiveureasebreathtestinapatientwhoisinfected
CytotoxinCagAcausesdirectCytotoxicity
Inducesinflammationviacytokines
Morphology
o Thereisachronicinflammatoryinfiltrate(plasmacells/leukocytes)admixedwith
activeinflammation(neutrophils)whichmaypredominate
o Lymphoidaggregates,somewithgerminalcenters,inthemucosa
o RegenerativeChangeofsurfaceandneckcellscausesanNuclear:Cytoplasmicratios
withhyperchromaticnuclei;difficulttodistinguishfromdysplasia
o IntestinalMetaplasia(gastricmucosacolumnar+gobletcellsofduodenum)
o Atrophyreferstothelossofgastricglands(Acid,IF,Cl)
o Dysplasiaisprecancerouschange
H.Pyloriorganismsseen AtrophycausesofGastrinProducingcells(inhibitorystimulus=secretion
ingastricgland
ofGastrin)whichleadstooverstimulationofECFcells
Metaplasiaalreadyactivatederroneousgeneproduction
Regenerativechangesrevupreproduction=riskoftransformation
Clinical
o Sxarepersistentacutegastritiswiththesamerange
o SerumGastrinisusuallynormalorslightlyelevated,lumenishypochloridic
o Autoimmuneshowscirculatingantibodies
o H.Pyloricanbeseenonbiopsy

LymphoidAggregatewithhypercellularmucosaof GlandssurroundedbyheavyNeutrophilicinfiltrate Gobletcellsincolumnarepithelium,loss

chronicgastritis (allthelittlepurpledots) ofgastricglands.Intestinalmetaplasia.

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PEPTICULCERDISEASE(BigRobbins816,BabyRobbins417)

PepticUlcers

Definition
o Histologicallydefinedbreachofthemucosathatextendsthroughthemuscularis
mucosaetoatleastthesubmucosa
Pathogenesis
o Chronic,oftensolitarylesionsoccurringtheGItractexposedtoacid/pepticjuices
Duodenum(~75%),Gastric(~20%),GastroesophagealJunction(~5%)

Gastriculcer.Singular, o CausedbyimbalancebetweenGIdefensesandacid/pepsin
Large,puckered NSAIDS=prostaglandins,ASAisadirectirritant
CigaretteSmoking=impairsmucosalbloodflowandhealing
EtOHhasnocausalrole,butastrongcorrelation
RapidGastricEmptying=acidexposuretoduodenum
DelayedGastricEmptying=pepticexposuretostomach
Punchedoutlesionwithstraightwalls
Hpylori=urease,CagA/VacA(Cytotoxic),proinflammatory=chronicgastritis
Morphology
o Roundtooval,sharplypunchedoutdefectwithstraightwalls
o Thebaseissmooth,andcansometimespenetratethewallofthestomach
o Puckeredmucosa,likeavolcaniccrater
o Areusuallysingularandlarge
Clinical
o Produceepigastricgnawing,burning,oraching;maypresentlikecardiaclikechestpain
o PepticUlcerTypes
DuodenalUlcers=Painisrelievedwithalkaliandfood,100%H.Pylori
GastricUlcers=Painisincreasedwithalkaliandfood,75%H.Pylori
Puckeredmucosalsurface o Withouttx,healingtakes15years
aroundthesmoothbased
lesion(lesionincenter)
o Withtx(H+PumpBlockers/OmeprazoleandH.PyloriAntibiotics)ulcershealinweeks
o Thiswasanentireslide,sowesayitagain:Ulcers=Infection,AntibioticsaretheCure

TUMORS(BigRobbins821,BabyRobbins420)

BenignTumors

Definition
o Anygrowththatprojectsabovethelevelofthemucosasurrounding
Morphology
o Gastricpolypsareuncommon,morecommoninthecolon,especiallyasyouage
o HyperplasticPolypsarethemostcommon(90%)andmaybesessile(withoutstalk)or
pedunculated(withstalk),areusuallysingular,andarenonneoplastic
o GastricAdenomas(10%)aretrueneoplasmswithdysplasticepithelium
Clinical
o Allincreasewithageandhaveasignificantlyincreasedriskwithchronicgastritis
o Maycontaincarcinomacentersandmustbebiopsiedfordiagnosis

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GastricAdenocarcinoma

Definition
o Mostcommonmalignantneoplasmofthestomach
Pathogenesis
o Largelyunknown,thoughlinkedtoallriskfactorsofchronicgastritis,inparticular:
Smoking,EtOH,H.Pylori,AutoimmuneGastritis
SmokedFish(Japan)withhighamountsofNitrosaminescandoitto
o Thereisanaturalprogressionfromacutegastritischronicgastritisintestinal
metaplasiadysplasiacarcinomathatisacceleratedparticularlybysmokingand
H.Pyloriinfections
SignetCellspathognomonic
forGastricCarcinoma
Morphology
o Antrum/Pylorus(50%);Lessercurvature(35%);GreaterCurvature(12%);Cardia(25%)
o EarlyGastricCarcinomaisconfinedtosubmucosal/mucosa;
o AdvancedGastricCarcinomaextendsthroughandbeyondthesubmucosaandhas
metastasized
Usuallyadvancedatthetimeofdiagnosis

Shrunken,thickenedwall(yellow o Therearetwosubtypes
arrow)redandulcerated.Looks Intestinal=glandformingcolumnarepitheliumfoundwithinthestomach;a
likealeatherbottlecalledlinitis
plastic.
productofintestinalmetaplasiafromHPyloriinfections,welldifferentiated
Diffuse=Poorlydifferentiated,stronglyinfiltrative,signetringonhistologyand
linitisplasticaongross,notlinkedtoH.Pyloriinfections
Clinical
o Typicallyaninsidiousonsettumor,earlysatietyandvomitingarelatesigns
Nitrosamines,H.Pylori,
o Outcomedependentondepthofinvasion:Early=95%,Advanced=15%5yearsurvival
SignetRingCell,Virchows
Node,LinitisPlastica o MetastaticSite
KrukenburgTumorsaremust VirchowsNodeisapariumbilicallymphnodepathognomonicformetastasis
knowforGastricTumors
KrukenburgTumoriswherethegastricadenocarcinomagoestotheovariea

Lymphoma

RareformofGastricCarcinoma,referredtoasaMALToma
AssociatedwithH.Pylori;infact,youshouldpickMALTomasoverGastrinomasforH.Pylori
Antibiotictreatmentyieldsremissionandrecovery

GastrointestinalStromalTumor=GIST

Rare,solidtumorgastricsubmucosal
Causedbyanoveractivationoftyrosinekinaseactivity
RelevantbecausetheycanbetreatedbyGleevac/Imatinib(tyrosinekinaseinhibitorforCML)

Metastasis

Fewtumorsmetastasizetothestomach;
Mostcommonisalymphoma(obviouslyotherthanMALToma)

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MALABSORPTIONSYNDROMES(BigRobbins842,BabyRobbins428)

CeliacSprue

Definition
o Immunediseasetowheatglutenleadingtodestructionofintestinalepithelia
Pathogenesis
o Sensitivitytogliadin,socalledwheatglutenfoundinrye,oat,andbarley
o LinkedtoaDQ2HLAhaplotype,suggestiveofgeneticrisk
o Tcellmediatedmalabsorptiondisorder
Morphology
o Moreproximalintestineisaffectedmorethanthedistalportions
o Thereareflatatrophicvilli(death)withelongatedcrypts(regeneration)
o Lymphocyteslitterthemucosalepithelium
Clinical
DermatitisHerpatiformis o Patientspresentwithmassivediarrhea,flatulence,weightloss,andfatigue
isadepositionofIgA o Patientsareinfancyupuntilmidadulthood
gliadincomplexesatthe o Linktotheskinblisteringdisease,DermatitisHerpatiformis
dermalepidermal
junction.
o Withdrawalofglutenfromthedietiscurativewithoutsequella

TropicalSprue

o Malabsorptivediarrheacausedbyinfectionofunknownorganism,suspectedEColi
LookslikeCeliacSprue,
butisfrominfection,not o RespondswelltoB12,Folate,andantibiotics
autoimmune o Usuallyinvolvesthedistalsmallintestine
o Thereisatrophicvilli,resemblingceliacdisease,butisnotanautoimmunedisease

WhippleDisease

Definition
o RaresystemicdisordercausedbyinfectionbyTropherymaWhippeliaffectingintestine,
jointsandCNS
Pathogenesis
o Unknown,organismisanactinomycetethatlivesinmacrophages
o RiskincreasesintheCaribbean,CaribbeanRuralFarmersDisease
Morphology
EMofbacilliin(arrow)and
outside(arrowhead) o Smallintestinalmucosaladenwithdistendmacrophagesinthelaminapropria
macrophage PASpositiveforundigested/incompletelysosomes
OrganismscanbeseenonEM
o Thesemacrophagesarefoundinjoints,brain,andheart
o Inflammationislowtoabsentthereisnoinflammatoryreaction,villiareintact
Clinical
o Respondswelltolongtermantibiotics
o Typicallymales(10:1)overfemales,andusuallyrural
VilliwithPASpositive
o Diarrhea,Malabsorption,andArthralgiatipyouoff,obstructionofGIorBiliaryTract
macrophagesinthelamina
propria

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LactaseDeficiency

Commonlycalledlactoseintolerant,thereisacongenitaloracquireddeficiencyoflactase
o Lactaseistheenterocyteapicalenzymethatdegradeslactose
o Lactoseisfoundinmilkandmilkproducts
CongenitalFormisusuallytheabsenceoftheenzyme,presentingwithfrothy,massivestoolsin
infants,shortlyaftereachfeeding
AcquiredFormshowsasteadydeclineinalmostallpatients,Americanblacksathighestrisk,
presentingwithfoulflatulenceanddiarrhea
Lactaseenzyme(Lactaid,forexample)takenwhendairyisconsumedalleviatessymptoms

AbetalipoproteinemianottalkedaboutinTulanesPathologyCourse

AutosomalrecessivedisordercorrespondingtotheabsenceoflipoproteinB
o LipoproteinBisrequiredforthefat/cholesteroltogetoutofepithelialcellsintoblood
Causesabuildupofcholesterolandlipidwithinenterocytes,leadingtolipidvacuolization
AlteredRBCmembranes(fromlackofcholesterolandlipid)causeburrcells
Withouttheabilitytogetfat,thepatientishypocholesteremic,hypolipidemic,andhavelow
levelsofVLDLandChylomicrons
Canpresentwithliverorneurologicdisorders

IDIOPATHICINFLAMMATORYBOWEL(BigRobbins846,BabyRobbins431)

Twodiseases,CrohnsDiseaseandUlcerativeColitis,withapoorlyunderstoodpathogenesis,resultin
inflammationofthebowel.Towhatthebodyisreactingtoisstilluncertain,somorphologyisthefocus.

CrohnsDisease

Definition
o Inflammatorydisorderofthebowelthatmayaffectmultiplesegmentswithunaffected
regionsinbetween,socalledskiplesions
Morphology
o Gross
SkipLesions;regionsofaffectedbowelwithnormalappearingmucosabetween
Rubbery,thickmucosalsurfaceleadingtofibrosisandstricture
NormalUlcerationNormal
MayaffectanyregionofGItract,frommouthtoanus
skippedlesions
o Micro
MucosalInflammationandulcerationwithintraepithelialneutrophils
ChronicMucosalDamage=villusblunting,atrophy,metaplasia
TransmuralInflammationwithlymphoidaggregates(givingrisetothickening)
NoncaseatingGranulomaseveninuninvolvedsegments
Clinical
Bariumenemashowsa o Intermittentattacksofdiarrhea,fever,abdominalpain,anorexia,andweightloss
stricture(arrow).Stricture o Occursinwhitesmorethanblacks,jewsmorethanotherwhites
isacomplicationofCrohns
butnotUC.stringsign
o WithterminalilealinvolvementB12deficiency,perniciousanemia,andmalabsorption
ofbilesaltsleadtocorrespondingsymptoms

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UlcerativeColitis

Definition
o Inflammatoryboweldiseaselocalizedtothecolon,formingulcerativelesionsina
continuousfashionandwithoutgranulomas
Morphology
o Therearenoskiplesions,andinvolvestherectumextendinginaretrogradefashion
o Psuedopolypsmaybeabundant,granulomasareabsent,cryptabscessespresent
ContinuousUlceration.
Everythingred,fromthe o Thinfloppywallbecausetheinflammationislimitedtothemucosa
rectumtothearrow,is ClinicalFindings
affected.Totheright
o Intermittentattacksofbloodymucoiddiarrheaandabdominalpain
(upstreamtowardssmall
intestine)oftheorange o Thereis,forsomereason,alinktoprimarySclerosingcholangitis(seeliver,below)
arrow is normal. o Increasedriskofcarcinomawithchronicinflammation

TUMORS(BigRobbins856,BabyRobbins436)

TumorsoftheSmallIntestine

Basically,theydonthappen
Whentheydo,eitheradenomas(benign)orcarcinomas(malignant)develop
Ifsymptomatic,theycauseobstructionandbleeding

BenignColonNeoplasms=AdenomatousPolyps=ColonicAdenomas

SessilePolypStalk
PedunculatedPolyp
ColonStalkPolyp
TubularPolypHistoSection
Benign,precancerouslesionsoftheluminalwall
Morphologies
o PedunculatedVsSessile
Pedunculatedpolypshaveastalk
riskforcancer
Sessilepolypsareflatandhavenostalk
riskforcancer
o TubularVsVillous
Tubularlookslikenormalcolon,withtubulesthroughoutthepolyp
riskforcancer
Villoushavefingerlikeprojectionsalloverthepolyp
riskforcancer
Tubulovilloushavecombinationsofboth
Presentation
o Maypresentwithoccultbloodinstool
o Warrantacolonoscopy,samplingofpolyps(removal)andhistologicsectioning
o Thepresentationismorebasedonwhatcausedthem:asinglepolypcommonwith
agingor1000polypsfromFAP.

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BenignNeoplasmsPolyposisSyndromes

FamilialAdenomatousPolyposis(FAP)thisoneistheonetoknow
o AutosomalDominantmutationoftheAPCgene
o Coloniscoveredinpolyps,100s1000sofpolypsinthecolon
o Highchanceofdysplasiacancer
o Prophylacticcolectomysuggested
o Hasvariants,asfollows
Gardner
TURcot=TURban=Brain
Gardner=theotherone=osteomas
FAPvariantwithbenignosteomasofthejaw,fibromatosisoftheliver,
benignepithelialinclusioncystsoftheskin
Turcots
Rare,autosomalrecessiveversionofFAP
1000sofpolypsinthecolon+independentbraintumor
(medulloblastoma,usually)
HereditaryNonpolyposisColorectalCancer(HNPCC)akaLynchSyndrome
AutosomalRecessivemutationoftheDNAmismatchrepairgene
Thesepeoplegetcoloncancer,butnotthepolyps
PeutzJeghers
FamilalAdenomatousPolyposis.The Hyperpigmentedlesionsonthelipsandoralmucosa
entirecolonisjustonegiantsheetof
adenomatouspolyps.Anyonecancarry
Endoscopyshowsbenignhamartomouspolypsinthesmallintestine
dysplasiaorcarcinoma. Lookelsewherefortumors,suchasthelungsorskin

ColonAdenocarcinoma

Pathogenesis
o Multiplegenemutationsandanypolyposissyndromecanleadtocoloncancer
p53,krasoncogene,DCCgene,APC(inFAP),DNAmismatch(HNPCC)
Morphology
o LeftSidedTumors
Presentwithalternatingdiarrheaandconstipationwithbloodinstool
Haveanapkinringnarrowing,calledapplecorenarrowingonbariumenema
Tumoriscircumferentialaroundlumen,causingastricture
Presentationissymptomaticearlierthanrightsidedtumors,andarelessfatal
o RightSidedTumors
Presentwithoccultbloodinthestoolonly
Fecesislooseenoughthatluminalstructuresdonotcauseobstruction
Theseareasymptomaticuntillate,wheretheyhavealreadymetastasized
ClinicalCourse
o HemeOccultBloodwarrantsascope,scopefindsatumororpolyp
o Resectioniscurative,unlessthetumorhasmetastasized(firstliver,theneverywhere)

CarcinoidTumors

SecreteserotonincausingaCarcinoidsyndrome=flushing,cramping,diarrhea,vomiting
IffromGI,mustmetastasizetoliverbeforetheybecomesymptomatic(liverdegrades5HT)
IffromLungsorAdrenal,metastasisisnotneeded
LookforSerotoninMetabolites(5HIAA)intheurine(5HT5HIAA)

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CONGENITALANDANTAMOICDISEASESOFTHECOLON(NoRobbinsPage,throwingthemtogether)

Volvulus

o Twistingofthebowelaboutitself
o Cancauseobstructionofthebowel
o Twistingofbloodvesselscanleadtoischemiaandinfarctionwhichthenresultin
perforation,peritonitisanddeath

BowelLoopedAroundBowel
Intussusception

Bowelshovedinsidebowel
o Telescopingofthebowelintoitself
o Cancauseobstructionofthebowelfromluminalnarrowing
o Intussusceptedsegmenthaspinchedbloodvessels,leadingtoischemiaandinfarction
whichthenresultinperforation,peritonitisanddeath
o Commonlyseeninkids(enlargedpeyerspatchesgetsnagged)butcanbeseeninadults
(usuallyacancerorapolyp)

MeckelsDiverticulum

o Mostcommoncongenitalabnormalityofthecolonandintestines
o Iswithin2feetfromtheileocecalvalveandis2cminsizein2%ofthepopulation,and
ofthat,2%willbecomecancerous
o Generallyanasymptomaticblindoutpouchingoftheintestinalwall,thoughtheymay
containpancreaticorgastricheterotopias(ectopicsites)whichcanbleed
RemnantoftheVitellineDuctandisaTrueDiverticulum
o Isasymptomaticuntilitbleeds;mostcommoncauseofGIbleedinginchildren
BlindoutpouchingSmallIntestines

HerschbrungsDisease=CongenitalMegacolon

Bariumenemaofcongenital
megacolon.Unaffectedsegment o
backtowardsthemouthis
dilated,affectedsegmentis
normal.Thestartoftheaffected
segmentismarkedbythe
arrow.
o Congenital
o Causedbythefailureofneuralcrestcellstomigratetothedistalcolon
Histologicdiagnosisisdependentonabsenceofgangliawithinbothmeisners
andauberbachsplexus
o AffectedSegmentisnormal,UnaffectedSegmentismassivelydilated
UnaffectedsegmentpushesstoolthroughGItract,andgetsbackedupatthe
affectedsegment,whichdilatestoaccumulatethebackedupstool
Therewillbeaperistalsis(becauseoftheabsenceoftheentericnervoussystem
ganglia)fromwheretheaffectedregionstarts,totheendofthecolon
Babypresentswithoutpassageofmuconiumandwithamegacolon
o MegacolonitselfmaybetoxicorfromChagasdisease,butbaby+megacolon=
Herschbrungsdisease
o Surgicalresectionoftheaffectedsegmentisrequired.

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GENERALIZEDFEATURESOFHEPATICDISEASE(BigRobbins879,BabyRobbins446)

Generalities

Bloodflow,MetabolicActivity,andfirstpassfromGIvulnerabilitytometabolic,toxic,
microbial,andneoplasticinsults
Liverhastheimmensecapacitytoregenerateandalargefunctionalreservesodiseasegoes
unnoticeduntilitisbothsevereandchronic
Mostoftenthereisaninsidiousonsetwithhepaticfailureoccurringinweekstoyears
MostcommoninsultsareHepC(50%),Alcohol(24%),andOtherHepViruses(4%)

PatternsOfInjury

DegenerationandIntracellularAccumulation
o Toxic/Immunologicinsultinducescellularswelling
o Severedamagecausesballooningdegenerationwithclumpsoforganelles
o Whenfataccumulateswithincellsitiscalledsteatosis
NecrosisandApoptosis
o Anysignificantinjurycancausenecrosis
o IschemicCoagulativeNecrosisleavesbehindmummifiedhepatocytes
o LyticNecrosis,aproductofballooningdegeneration,leavesbehindcellulardebris
o FrequentlyexhibitszonaldistributionasinCentrilobularnecrosis(aroundportalvein)
o Submassive(entirelobule)ormassive(mostoftheliver)necrosisisoftenaccompanied
byfrank,acute,hepaticfailure
Inflammation
o Aka,hepatitis,itisanyinflammationoftheliver
o Kupfercells(themacrophages)andLymphocytesliveintheliver
o Granulomasmayformtoforeignbodies,organisms,ordugs
Regeneration
o Amazingcapacitytoregeneratefromlivinghepatocyteproliferation(nostemcells)
o Occursinallbutmostfulminantdiseasesandchronicconditions
Fibrosis
o Whenitdoesntregenerate,itscars
o Fibrosisisgenerallyirreversible(seecirrhosisforexception)
o Dividesliverintofunctionalregeneratingnodulessurroundedbyfibrosis=cirrhosis

LiverFailure

Definition
o Despitetheincrediblefunctionalreserve,when8090%ofhepaticfunctionislost,
hepaticfailureensues
Causes
o MassiveHepaticNecrosisoftendruginduced(acetaminophen,Rifampin)leadingto
hepaticinsufficiency;HepCdoesnotcausethisrapiddestruction

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o ChronicLiverDiseaseismostcommonroutetohepaticfailureandisaproductof
relentlessHepatitisinfectionsresultingincirrhosis(usuallyHepC)
o HepaticDysfunctionwithoutNecrosisoccurswhereviablehepatocytesfailtodotheir
job,asinReyeSyndrome
ClinicalFeatures
o Jaundiceliverprocessesbilirubin,whichnowaccumulates,turningthescleraofthe
eyeandpigmentationoftheskinyellow,mayconjugatedorunconjugated
o HypoalbuminemiaAlbumen(madebytheliver)EdemafromOncoticPressure
o HyperammonemiaNH3fromimpaireduricacidcycleleadstocerebraldysfunction/
hepaticencephalitis
o FetorHepatitismuskyodor,sweetandsourscenttothebody
o CoagulopathyClottingfactorsmadebyliverleadstobleeding
o HepaticEncephalopathy
NH3leadstogeneraledemaandneurotransmissionintheCNS
Fluctuatingneurologicsignsincluderigidity,hyprereflexia,andasterixis
Mayleadtoalteredmentalstatus,coma,ordeath
ChangesarenotpermanentandmaybereversedwithNH3
o HepatorenalSyndrome
RenalFailureasamultifactorialresultofliverfailure
BUN,Cr,GFR,withaUrinarySodium,Protein,andtheabilityto
concentrateurine(differentialfromacutetubularnecrosis)
Oftenaccompaniesasignificanthepaticstressor(infection,GIbleed,surgery)

Cirrhosis

DefinitionandCharacteristics
o Anendstagechronicliverdiseasemarkedby:
BridgingFibrousSeptae=lotsoffibrosislinkedtogetherbetweenportalveins
ParenchymalNodules=islandsofproliferatinghepatocytestrappedinfibrosis
GlobalDisruptionofhepaticarchitecturewithvascularreorganization
Etiology
AlcoholLiverDisease 6070% Oncepresent,theoriginalcausemaybe
morphologicallyindistinguishable.Agoodsource
ViralHepaticSyndrome 10%
ismicronodular(usuallyEtOH)versus
SomeRareDisorders <1% macronodular(usuallyHepatitis)
Cryptogenic,Wedontknow 15%
Pathogenesis
o StellateCells(ItoCells)existwithinthespaceofdisseandnormallystoreVitaminA
o StellatecellsreceiveaproinflammatorysignalfromKupfercells,causingthemto
switchfromVitaminA/FatLikecellstofibroblastlikecells
o CollagenDepositionactsasscartissue,butirregularlybridgesseptaetogether
Thisprocess,oncethoughtirreversible,maybereversibleafterall
Hepatocytespossessmetalloproteinasesrequiredtodegrade(slowly)collagen
o VascularReorganizationcreateschannelsaroundfibroticseptaethatmaybypass
hepaticcords(andescapefiltration)orleadtoportalsystemicshunts

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Clinical
o Cirrhosismaybeclinicallysilentforyearsuntilitpresentswith
Anorexia Osteoporosis HepaticFailure HepatocellularCarcinoma
Weightloss Weakness PortalHypertension(below)
(below)

PortalHypertension

Definition
o ResistancetobloodflowthroughthelivercausingabackupofGIorganbloodflow
andarequirementofcollateralcirculation
Causes
o Prehepatic=stenosis,compression,orthrombosisofportalvein
o Posthepatic=rightsidedheartfailureandthenutmegliver
o Intrahepatic=mostdominantcauseingeneraliscirrhosis.Schistosomiasisispossible
andisprevalentaroundtheworld;cirrhosiswinsbyalongshotinUS.
Consequences
o Ascites
Excesscollectionoffluidinperitoneum,fluidonthebelly
VenousHydrostaticpressurepreventsresorptionoffluidonthevenousside,
exacerbatedbythevenouscapillarypressurefromHypoalbuminemia
Lymphaticdrainageinsufficienttocarryfluidaway
o PortosystemicShunts
NormallyunusedchannelslinkingGI/portaltosystemiccirculation
EsophagealVaricesmostdangerous(riskofhemorrhage)
Hemorrhoidsarepainful,foundinanus/rectum
CaputMedusaisdilationofveinsontheabdomen
o CongestiveSplenomegaly=big,wet,red,palpablespleen
o HepaticEncephalopathy=discussedabove

Jaundice

Jaundiceiscausedbyhyperbilirubinemia,andisoftenassociatedwithcholestasisandincreasedbile
salts.WediscussbilirubinpathologyfirstinJaundicethendiscussbilesaltpathologyinCholestasis

BilirubinPhysiology
o Bilirubinistheendproduceofhemedegradation(RBClysis)
o Extrahepaticbilirubinbindstoalbumin
o HepatocellularuptakeoccursandbilirubingetsconjugatedviaUGT1
o Conjugatedbilirubiniswatersoluble,transportedintobile,andexcretedintoGItract
o Bacteriadeconjugatebilirubinintocolorlessurobilinogenandpigmentslostinstool
o Bilirubinrepresentsonlyasmallpartofbile;therestisBileAcids
LabValues
o ElevatedBilirubinintheserum
o ElevatedAST/ALTindicateshepatocellularinjury(probablynecrosis)
o DifferentiatefromAlkPhoswhichpointstobiliarypathology

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BilirubinPathology
o Jaundiceoccurswhenthereismorebilirubinbeingformedthanbeinglost;thedefect
maybeinproduction(systemic),conjugation(liver),orexcretion(biliary)
ExcessiveProduction,asinhemolysis(UnconjugatedBilirubin)
Secretionand/orBileFlow(ConjugatedBilirubin)
ReducedHepatocyteUptake(UnconjugatedBilirubin)
ImpairedConjugation(UnconjugatedBilirubin)
o Hasapigment,sowhenelevated,depositsinalltissues,givingrisetoyellowskin
(jaundice)andyellowsclera(icterus)
o UnconjugatedBilirubinislipidsoluble,highlytoxic,notexcretablethroughtheurine,
and,whenitaccumulatesinthebrain,causeskernicterus(whichisbad)
o ConjugatedBilirubiniswatersoluble,nontoxic,andexcretableintheurineiflevelsrise,
producingadarkcoloredurine.
SpecificBilirubinDiseases
o NeonatalJaundice
Neonatalconjugationmechanismsarenonfunctionaluntil~2weeks
Mildunconjugatedhyperbilirubinemiaisnormal,andshouldresolvequickly
o ErythroblastosisFetalis
CausedbyRhmomsgivingbirthtoRh+babies
Massivehemolysis=unconjugatedbilirubininbaby
Noconjugationfunction=substantialbilirubin=kernicterus
o CriglerNajjarType1
CompleteAbsenceoftheUGTProteinthatconjugatesbilirubin
Fatalwithoutatransplantin18monthsfromkernicterus
Unconjugated
Feceswillbepale(nopigmentation)
moredangerous
unconjugatedbilirubin,AutosomalRecessive
o CriglerNajjarType2
Lesssevere,nonfatal,mutationofUGTproteinthatconjugatesbilirubin
Patientsdevelopnormally,andmayhaveperiodicboutsofjaundice
Unconjugatedbilirubin,AutosomalRecessive
o Gilbert
MutationofTATABoxoftheUGTgenecausingUptakeandConjugation
Noclinicalconsequenceexceptforperiodicjaundicefollowingstressor
UnconjugatedBilirubin,AutosomalRecessive
o DubinJohnsonMostCommonlyTestedonBoardsofallthesediseases
AbsenceofMRP2,transporterthatsecretesconjugatedbilirubinintobile
Normallifeexpectancywithperiodicjaundice,darkpigmentedliver
Bilirubinisconjugated,butnotexcreted;ConjugatedBilirubin
Conjugated o Rotor
lessdangerous Asymptomaticmutationinmultipletransportersforuptakeandsecretion
SameasDubinJohnson,withoutthedarkpigmentation
ConjugatedBilirubin,AutosomalRecessive

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Cholestasis

Definition
o Literally,stoppageofthebiliarytreemeaningthattheflowthroughthebileductsis
slowedorstopped
BileAcidPhysiology
o PrimarybileacidsareCholicAcidandChenodeoxycholicAcidwhichgetsecretedwith
lipidscalledlecithins
o BilesaltssolubilizecholesterolandfatsintheGItract
o Bilesaltsaremadefromcholesterol,aresecretedintobile,excretedintoGItract,and
aremostlyreabsorbedthroughenterohepaticcirculation
o Bilesaltslostinstoolrepresentstheonlyegressforcholesterolfromthebody
BileAcidPathology
o ExtrahepaticCholestasis=Anythingthatblocksthelumen(gallstones,tumor)will
obstructflow;isamendabletosurgery
o IntrahepaticCholestasis=Anythingthatfailstoproducebilefromtheliver(MRP2Gene
inDubinJohnson)willdecreaseflow;notamendabletosurgery
o Ifsomethingblockstheflowofbileacidsoutoftheliver,likelytherewillbeabackupof
bilirubinaswell,sojaundiceislikelytobeseen
Morphology
o Bileaccumulatesintheliver,wheninsidethehepatocytes=featherydegeneration
o Obstructioncausesdilationofupstreamtreeandbilelakeswithintheliver
o Unrelievedobstructionwillcausesfibrosis
Clinical
o Jaundice(obstructiontobilirubinegress)
o Pruritis(serumbileacidsanddepositintotheskin)
o Xanthomas(cholesteroldepositsinskin)
o SerumAlkalinePhosphatase(localbiliarydestructionfromstagnantbilesalts)

GENERALFEATURESANDSYNDROMES
Disease Features
LiverFailure Liverhaslargefunctionalreservoir,requireslossof8090%offunctionalliver
Causedbymassivenecrosisorlongtermprogressivefibrosis/cirrhosis
Resultsinhepaticencephalopathy(fromNH3),Hepatorenalsyndrome,
hypoalbuminemia,anddelayinclottingtimes(PTTfromclottingfactors)
Cirrhosis Definedasbridgingfibrosisformingislandsofregeneratinghepatocytes(nodular)
Causedbylongtermchronicinflammation(EtOH,HepB,RareGenetic,Cryptogenic)
Itocells(vitaminAstoringfatcells)turnintomyofibroblasts,andlaydowncollagen
PresentswithLiverFailure,PortalHypertension,Hepatocellularcarcinoma
Portal Obstructionofbloodflowthroughtheliverfrompathologicchanges
Hypertension Portocavalshuntsareformed(hemorrhoids,esophagealvarices,caputmedusa)
Liverbecomesunderperfusedfornutrientsandcannotdetoxifybloodaswell
Jaundice Skinturnsyellow(jaundice)andscleraofeyeturnsyellow(icterus)
and Causedbybackupofbile(intrahepaticorExtrahepatic),bilirubincausesyellowcolor
Cholestasis BileSaltsalsobackup=damagetobiliarytress,xanthomas,andpruritis

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INFECTIOUSDISORDERS(BigRobbins890,BabyRobbins452)
HepA

Benign,selflimiting,febrilejaundicetransmittedthroughthefecaloralroute
Itdoesnotproducechronicdiseasenorcarrierstates
ItisasmallssRNApicornaviruswithanIcosahedralcaspid
Transmittedfecaloralinthewatersupplywithhumanwaste,foodpreparersthatdontwash
theirhands,orshellfishthatconcentratethevirusfoundincontaminatedwater
Patientshedsvirusfor23weeksbeforeand1weekafteronsetofjaundice
IgMwithdiseaseonsetmarkingacutedisease,peaksasfecalsheddingstops,andIgG
antibodiespersist,perhapsforlife,makingthevaccinehighlyeffective

HepBLongwinded,complicated,butyouhavetoknowitall,veryBoardRelevant

ViralInfo,Structure,andGeneProducts
Schematicforthepiecesof
virus
InfectionandPathogenesis
Mostpeoplerecoverquickly,
somestayashealthycarriersa
smallfractiongoontochronic
persistentinfection),anda
minisculefractiongoesto
fulminatedisease
o HBVisa42nm,spherical,doublelayeredDaneParticleandisanincompletedsDNA
o ACoreProtein(HepBCoreAntigen,HBcAg)staysininfectedhepatocytes
o APreCoreProtein(HepBeAntigen,HBeAg)istargetforreleaseintoblood
o ASurfaceEnvelopeGlycoprotein(HepBSurfaceAntigen,HBsAg)isproducedinmass
quantitiesinthehepatocytes,causinggroundglassappearance
o ADNApolymerasewithreversetranscriptasecapability(DNAviralreplicationoccurs
throughaRNAintermediate)
o ProteinX(HBx)necessaryforviralreplication&implicatedinhepatocellularcarcinoma
o HepBdoesnotcausehepatocyteinjury;itistheimmuneresponse(CD8CytotoxicT
Cells)toinfectedhepatocytesthatcauseshepatocyteinjury
Thestrongertheimmuneresponsetheworsetheacutehepatitisbutthelower
theriskforchroniccarrierstate
RiskofcarrierstateforNeonates,Immunocompromised
o HepBishearty,andistransmittedthroughsemen,saliva,urine,sweat,blood,lactation
riskforIVDrugUsers,AccidentalNeedlestick,homosexualmales
VerticalTransmissionfrommomtobabyduringbirthispossible
o HepBhasaprolongedincubation(624weeks),riskofunknownviralspread
o Infectionhas4possibilities
AcuteHepatitisWithResolution=nastyjaundiceandterriblesymptoms,but
thevirusiscleared,andthereisnochronicstate(mostcommon,95%)
ChronicHepatitis=thereisaweakimmuneresponse,mildhepatitis,buta
persistentcarrierstatethatlastsforever(4%)
FulminantHepatitis+MassiveNecrosis=fairlyrareforHepB,notgood(<1%)
HepD=HepDmusthavecoinfectionwithHepBtogetintoahepatocyte
o Onceinfected,HepBintegratesintohostDNAandundergoesreplications
o HepXprotein+chronicinflammation/hepatocyteturnovercanleadtobothcirrhosisor
Hepatocellularcarcinoma

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Serology
o HBsAgoccursbeforesymptoms,peaksduringovertdisease,declinesasAntiHBsAgrise
o HBeAg,HBVDNA,andDNApolymerasedemonstrateactivereplicationandinfectivity
o IgMappearsfirst,IgMwillbereplacedbyIgGforAntiEveryAntigen
o IgGwillnotbedetectableforsomemonths,whiletheantigenmaynoteither,they
canceleachotherduringthiswindowperiod,thoughbotharepresent
PersistenceofIgGmakesavaccinepossible
o ThepersistenceofHBsAgandHBVDNAsignifycontinuedchronicinfection

HepC

Small,enveloped,ssRNAvirus
Causesamildtoabsentacuteresponsebutisthemostcommoncauseofbloodbornechronic
liverdisease;italmostalwaysstayschronic
WithpoorfidelityoftheRNApolymerase,mutationsareabundant,andthusAntiHCVIgGdoes
NOTconveyimmunity(thereisnovaccine)
PersistentinfectionandChronicHepatitisaretherulewithanRiskforcirrhosis
PresenceofRNA,AntiHCVIgGarenotalwaysdetectable,fluctuating(spikeswithnearnormal
intervalperiods)levelsofserumaminotransferaseisalmostpathognomonic
Thediseasecannowbetreatedwithinterferonandribivarinwhichcanbepotentially
curative(viralDNAcountremains0after6monthsofterminatingtreatment)

HepD

ThecrippleHepVirus
Taxonomicallydistinct,butwhollydependentonHepBinfectionandgeneexpressionfor
multiplication
HepDmakestheHepBinfectionworseinseverity,chronicity,andriskofHCC

ClinicopathologicSyndromes

AcuteAsymptomaticInfectionwithRecovery
o Yougetinfected,youdontknowit,butyoufindoutlateronserologyexam
o CommoninHepAorHepBinkids(theydontgetJaundiced)
o Thisiswhatwewantwhenwegivethevaccine
AcuteSymptomaticInfectionwithRecovery
o AnyHepviruscanpresentthisway,almostalwaysHepA,usuallyHepB,rarelyHepC
o IncubationPhase=circulatingantigensandantibodies
o Preicteric=beforethejaundice,peoplegetnausea,vomiting,fever,chills,headache,
arthralgiaandrash(thelasttwofromimmunedeposition)
o Icteric=thejaundice.Othersymptomsgetbetter,buttheyturnyellowandtheirurine
getsdark,aproductofconjugatedbilirubin(noriskforkernicterus)
o Convalescence=takethatviruses!

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ChronicHepatitis
o Symptomatic,Serologic,orBiochemicalevidenceofpersistentinfection
o RiskwithTCellCompromisedinHepB,itistheGeneralRuleforHepC,andbarely
everoccursinHepA,ifatall
o Carriers,whethersymptomaticornot,canshedvirusandinfectothers
o Etiologydeterminesprogresstocirrhosis(HepCdoesitalot,HepBnotsomuch)
FulminantHepatitis
o HepaticInsufficiencyprogressesfromonsettohepaticencephalopathyin23weeks
o ViralFulminatehepatitisaccountsfor12%ofallfulminatecases,withHepBandHepC
accountingfor~100%ofviralcases
o Drugs/Toxins(50%)andmiscellaneousmakeupthedifference

MorphologyofHepatitis

Acute
o Hepatocytesshowdiffuseswellingcalledballooningdegeneration
o Cholestasisisaninconsistentfinding,oftencausedbybileorpigmentplugs
o Necrosiscanbeseenwithcytolysisprecedingmacrophageaggregates
o Apoptosis,mediatedbyTcells,causeshrunken,highlyeosinophilicnuclei
o InflammatoryCellscanbeseenwithinthelumenandmayspillintoparenchymacausing
BallooningDegenerationand
necrosis,termedinterfacehepatitis
lossoflobulararchitecturein
acuteviralhepatitis Chronic
o Steatosis=fattychangewithinthehepatocytes
o GroundGlassCells=evenlarger,moreballoonedthanballooningdegeneration
o InterfaceHepatitis+Bridgingnecrosisareharbingersofliverfailure
o Fibrousdepositionreplacesthenecrosisandisthemarkerofirreversibledamage
PeriportalFibrosisstatsitoff,thenregionsoffibrosisbegintoconnect,called
portaltractexpansion,
interfacehepatitis,lymphoid bridgingfibrosis,untiltherearesmallislandsofregeneratinghepatocytes
aggregate surroundedbyfibrosis(cirrhosis)
Fulminate
o Widespreadnecrosisinvariablepatternsdependentonetiology(red,mushy,shrunken)
o MassiveinfluxofPMNs,followedbylymphocytes,witheventualregeneration/fibrosis
o Hepatocytedrivenrecoverymaybenearcompleteifthepatientliveslongenough(4
weeks)withpreservationofparenchymalarchitecture.

Hepaticveinsandarteriesarecloser
togetherasaresultofnecrosisand

lossofarchitecture,lotsofpurpledots
areinflammatorycells(acraploadof
them)

Diagrammaticrepresentationofthechangesin
chronichepatitis.Usethistogetwhatis
meantbythedifferentterminologyinboth
chronicandacute.Foramoreclearpictureof
both,seeimages1817inBigRobbins

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MorphologyofHepatitis

AcuteHepatitis.Thereisalossof
lobulararchitecture.Therearemany
mitosesashepatocytesdivideto
initiaterepair.Architecturewillbe
restored.Thisisnonspecificinjury
LymphoidAggregates.Theportal GroundGlassAppearance.The
triadhassignificantleukocytic hepatocytesareenlarged,someare
infiltratethathasspilledoverintothewithoutnuclei,andhaveapinkfill.
parenchyma.Alymphoidaggregate Alsoonthisslidearethesandynuclei.
hasformed,indicativeofHepC ThisisindicativeofHepB

Steatosis.Thelargevacuoles(white BileDuctInvolvement.Thereis InterfaceHepatitis.Thelymphocytes

spaces)arepresentwithinhepatocytes. alymphocyticinfiltrate fromaportaltriad(youcanseethe
Thecellsarefilledwithfat.Indicativeof
surroundingthebileduct,which bileduct)buttupagainstthelimiting
fattychange(EtOH,HepC) hasanabnormalshape plateofhepatocytes.Thereis
(amorphousfromcircular). necrosisofthehepatocytesonthe
IndicativeofHepC rim,butnolymphocyteswithin

parenchyma

Grade1PeriportalFibrosis.Inflammatory Grade2SeptalFibrosis.Thefibrosis Grade3BridgingFibrosis.Fibrosis Grade4Nodulesrepresentgrade4.Purple

cellscomeoutoftheportaltracts,but spillsintotheparenchyma,but fromdifferentportaltractsbeginto islandsofregeneratinghepatocytes
doesnotspillintotheparenchyma;there irregularly,andneartheportaltracts connectwithsmalltractsoffibrosis. surroundedbyfibrosisindicatedGrade4

isonlyinterfacehepatitiswithinterface hepatitis,cirrhosis.
necrosis.
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AUTOIMMUNEHEPATITIS(BigRobbins903,Baby458)

AutoimmuneHepatitis

FemalePredominancewithbimodalagepresentation(adolescenceandperimenopausal)
Absenceofviralserologicmarkersthoughthereissymptomologyofhepaticinjuryandthe
presenceofIgM
AutoantibodiestoANA(antinuclear)andSMA(smoothmuscle)presentinblood
Maybeasymptomatic,butclinicalillnessiscommonatpresentationthoughfulminateisrare
o Weightloss,pruritis,myalgia,rash;typicalhepatitisandautoimmunesymptoms
o Jaundicemaybepresent(20%30%)
Autoimmunedestructionofhepatocytesmaybeindistinguishablefromcholangitis
Respondswelltoimmunotherapy

DRUGINDUCEDLIVERDISEASE(BigRobbins903,Baby458)

Generalities

Drugsmayinjureliverbydirecttoxicity,conversiontoatoxin,haptenimmunologicrxn
Druginducedchronichepatitisisindistinguishablefromchronicviralhepatitis;serologic
markersarerequiredfordiagnosisanddifferential
Maypresentwithhepatocytenecrosis,hepatitis,cholestasis,fibrosisoritcouldbeinsidious
Usually,removalofthetoxinleadstorecovery
Heresasample,dontmemorizethis,butdotakealookatit

Hepatocellular Damage Examples

Microvesicular fatty change
Macrovesicular fatty change
Centrilobular necrosis
Hepatitis, acute and chronic
Fibrosis-cirrhosis
Granuloma formation
Cholestasis (with or without
hepatocellular injury)
AlcoholicLiverDisease
Tetracycline, salicylates, yellow phosphorus, ethanol
Ethanol, methotrexate, amiodarone
Bromobenzene, CCl4, acetaminophen, halothane, rifampin
Methyldopa, isoniazid, nitrofurantoin, phenytoin, oxyphenisatin
Ethanol, methotrexate, amiodarone, most drugs that cause chronic hepatitis
Sulfonamides, methyldopa, quinidine, phenylbutazone, hydralazine, allopurinol
Chlorpromazine, anabolic steroids, erythromycin estolate, oral contraceptives, organic
arsenicals

Morphologies
o HepaticSteatosis
Consumptionofalcoholcauses3majorchangesthatliverfatcontent
Shiftingawayfromcatabolism,switchingtolipidsynthesis(makefat)
Impairedformationandsecretionoflipoproteins(fatcantleave)
PeripheralCatabolismoffat(morefatcomesbacktoliver)
Liverbecomesyellow,large,softandgreasy

Zoomedinviewofsteatosis, Microscopic=macrovesicularnodules(chronic)ormicrovascular(acute)
largevacuoleswithin
Abstinence=Recovery
parenchyma

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BallooningDegeneration,MalloryBodiesandaNeutrophilicreaction,when
o AlcoholicHepatitis together inadrinker,arepathognomonicforEtOHHepatitis
Characterizedby4changes:
HepatocyteSwellingandNecrosis=directhepatocytetoxicityresultsin
ballooningdegeneration
MalloryBodies=eosinophilicinclusionsofdyinghepatocytesare
characteristicof,butnotuniquetoalcohol
NeutrophilicRxn=Alcohol+itsmetabolite,Acetaldehyde,inducechanges
Zoomedimageof inhepatocellularproteinsleadingtoanimmunologicrxn.Lymphocytes
eosinophilicinclusions,
MalloryBodies entertheportaltractsandspillintoparenchyma
Fibrosis=activationofstellatecells,particularlysinusoidalperivenular
fibrosis;periportalmaypredominate.Fibrosisprogressestocirrhosis.
Liverismottledred,stainedwithbile,&possessnodulesandfibrosis(portends
comingcirrhosis)
Abstinence=Recovery
o AlcoholicCirrhosis
Finalandirreversiblechangeofcontinuedfibrosis

Fattyliver(white)withsome Presentswithamicronodularliver(opposedtoHepVirus)
fibrosis(blue) RegeneratingHepatocytestrappedbybridgingfibrosis
Grossly,theliverisshrunken,brown,nonfatty,andnodular

Pathogenesis NodularLiver
o EtOH=calories,displacingvitamins(B12)
o InductionofP450=Toxicmetabolitesofnormallysafedrugs
o EtOHandAcetaldehydearedirectlytoxicandimmunogenictomitochondriaand
cytoskeletonsofhepatocytes
ClinicalFeatures
o HepaticSteatosis
Usuallyasymptomatic,mayhavebilirubinandAlkPhos
Withdrawaliscurative
Takestimeandisinsidiousifthereisanyevidenceofdiseaseatall
o AlcoholicHepatitis
Isacuteandsymptomatic,especiallyfollowingaboutofheavydrinking

Cirrhosis.Islandsof Maybeminimal,fulminate,orsomewhereinbetween
RegeneratingHepatocytes Mimicsotheracutehepatitis(anorexia,malaise,jaundice,AST/ALT)
(pink)surroundedbyfibrosis
(blue)
Outlookisunpredictable,thoughrepeatedboutstendstowardscirrhosis
o AlcoholicCirrhosis
Sameasotherformsofcirrhosis
PortalHTN,HepaticEncephalopathy,Ascites,HepaticFailure,etc.
VariableProgressiontohepaticfailureanddeath,worsewithstressor
o Deathresultsfromliverfailure,hemorrhage,orcoma,alldiseasessecondarytothe
cirrhosis.

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METABOLICLIVERDISEASE(BigRobbins907,BabyRobbins460)

NonalcoholicFattyLiver(NAFL)andNonAlcoholicSteatoHepatitis(NASH) BallooningDegeneration,MalloryBodiesanda
Neutrophilicreaction,whentogetherbutnotina
Morphologyofalcoholicfattyliverwithoutthehistoryofdrinking drinker,arepathognomonicforNASH

Linkedtoobesity,dyslipidemia,insulinresistance,andtype2diabetes
o Ifthepatientisfatandunhealthy,theirlivergetsfattyandunhealthy
Steatohepatitis=ballooningdegeneration,PMNs+Steatosis,MalloryBodies,Sinusoidalfibrosis
o IfthevignettescreamsALCOHOLICHEPATITIS,butthepatientdoesntdrink,pickthis
Cirrhosismayoccur,thoughoftenasymptomaticexceptforAST+NeutrophilicLeukocytosis

Hemachromatosis

Definition
o Excessiveaccumulationofbodyironwhichgetsdepositedintoparenchymalorgans
Pathogenesis
o PrimaryHemachromatosis
NormalIron26gbodyIron,diseaseis2050gbodyiron,1/3intheliver
Thereisnowaytogetironoutofthebodyonceitgetsin
Thereislossofdietaryironregulationleadingtoaccumulationofiron
MutationintheHFEgenecodingforaCystineTyrosine@282;C282Y
Codesthewehaveenoughironsignal
Withhomozygousloss,cryptcellprogramming=getmoreiron
StainedwithPrussianblue,ironis Ironisdirectlytoxictohosttissues,yetthemechanismisreversible
demonstratedinearlydiseasewith
RemovalofIron=healing
maintenanceofhepaticarchitecture
Diseaseisautosomalrecessive
o SecondaryHemosiderosis
HemolyticAnemiawithineffectiveerythropoiesiscausesironreleased(from
hemolysis)anddietaryintake(tomakemoreRBCs)
Transfusionscontainingirondoublewhatistakeninbythediet
Morphology
o Irondepositioninorgans(inorder):liver,pancreas,myocardium,pituitary,thyroid,skin
o Cirrhosisoftheliverandfibrosisofthepancreas
o Liverislarger,dense,andchocolatebrownbeforefibrosis;shrunken,nodular,and
blackafterfibrosis.
Clinical
o Typicaltriad=micronodularcirrhosis(liver),frankdiabetes(pancreaticfibrosis)and
bronzeskin(melaninproduction)
o CardiacDysfunction,Hepatomegaly,abdominalpain,andgynecomastiaarepossible
o Alwaysscreensiblingsofdiagnosedpatient
o ChronicPhlebotomy(bloodletting)istheonlytherapyavailable

Blackliver(latedisease,top)

brownliver(earlydisease,bottom)

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WilsonsDisease

Definition
Ballooning+MalloryBodies o Autosomalrecessivedisorderwithaccumulationofcopperintheliver,brain,andeye
Pathogenesis
o AutosomalRecessivemutationofacopperATPasecalledATP7Bonchromosome13
Excesscoppercannotbeexcretedfromhepatocytesintobileforelimination
o Multiplemutationshavebeenfound,patientsareusuallycompoundheterozygotes
(missingpieceAononechromosomeandmissingpieceBontheother)
o Copperhandlingcapacityofceruplasminisexceededat~5yearsofagewhereacute
illnessresultsfromcopperspillingintothebloodstreamanddepositinginorgans
Ballooningdegeneration,
MalloryBodies,Portal Morphology
TractInflammation o Steatosis,AcuteHepatitis,andChronicHepatitishavenouniquecharacteristics
o SteatosisandMalloryBodies(usuallysuggestiveofEtOH)maybepresentinWilsons
o Coppercontent>250ug/gdryweightliverisrequiredfordiagnosis
o Copperdepositsinorgans
BasalGangliaDeposits=atrophyofbasalganglia,especiallyputamen
KayserFleischerRings=cornealdeposits,ringsinthecornea
Clinical
o Firstpresentationisinthefirsttwodecadesoflife(usuallyaround20)
o serumceruplasmin,hepaticcopper,urinecopper(serumCuisuseless)
Rhodaninestainscopperas o Psychosisorparkinsonismispossible(basalganglia)
redflakes,whichare o HemolysisfromCuinbloodrevealsSchistiocytes
diffuselyscattered
o Transplantationandcopperchelationaretherapies

1AntitrypsinDeficiency

Definition
o AutosomalCodominantdisorderleadingtothemisfoldingoftheproteaseinhibitor1
antitrypsin(1AT)whichcausesemphysemaandhepaticdisease
Pathogenesis
o 1ATisa394aaproteaseinhibitor(Pi)withmultiplepolymorphisms
PiMisthenormalfunctioningprotein
PiZcreatesdiseasesstates
HomoPiMMbetterthanHeteroPiMZbetterthanHomoPiZZ
PASPositivecytoplasmic o PiZZcausesmisfoldingandentrapmentwithintheER,circulatinglevelsof1AT
inclusions(theredthings)
Morphology
o RoundtoovalPASpositivecytoplasmicinclusionsinhepatocytes=pathognomonic
o Neonatalhepatitis,childhoodfibrosis,oranystageofhepatitisatanyagecanbeseen
Clinical
o NeonatalHepatitisandCholestaticJaundice(1020%ofnewbornswithdeficiency)
o Riskforcirrhosis,HCC,andemphysema
Immunohistochemistry o Avoidsmoking(emphysema),getalivertransplant(cirrhosis,HCC,andPi)
for1AT
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INTRAHEPATICBILIARYTRACTDISEASE(BigRobbins913,BabyRobbins464)

SecondaryBiliaryCirrhosis

Whenaninitialincitingevenofthebiliarytreeinducesfibrosisandcirrhosisoftheliver
Causedbyobstruction(cholelithiasis,tumors,strictures)orbybiliaryatresia
Producesfirstcholestasis,whichcanthenleadtoperiportalfibrosis,cirrhosis,andcholangitis
Ascendinginfection,ifpresent,causesintenseinflammatoryinfiltrate
Jaundice+icterusmaybepresent

PrimaryBiliaryCirrhosisWomen,Granulomas,AMAantibodies

Chronic,progressive,oftenfatalCholestaticdisease
Primaryfeatureisnonsupparativeinflammatorydestructionofmediumsizedbileducts
Autoimmune(E2subunitofthepyruvateDehydrogenasecomplex)
Diseaseofmiddleagedwomen(thoughonsetofinjuryismuchyounger)
Thereisamassiveleukocyticinfiltrate(lymphocytes,macrophages,plasmacells)inportal
tracts,givingrisetodestructionandfibrosis
o Upstream=dilation,ductularproliferation,andnecrosis
o Granulomasmayformaroundbiletracts
o Overdecadesbridgingfibrosisgivesrisetocirrhosis
Initialstagesmayshowgreen,bilestainedliver,latestagesareindistinguishablefromother
causesofcirrhosis
InsidiousOnset,withcirrhosis,portalHTN,andhepaticencephalopathyfoundin4th/5thdecades
Deathresultsfromrupturedvarices,encephalopathy,orinfection
LabsshowAlkPhos,AntimitochondrialAntibodies,Cholesterol

PrimarySclerosingCholangitisMen,UlcerativeColitis,Noantibodies

Unknownpathogenesisofafibrosingcholangitisofbileductswithalymphocyticinfiltrate,
progressiveatrophyofbileductepithelium,andobliterationofthelumen
Thereisconcentricperiductalfibrosis(onionskinning)followedbyluminalabsence
Withdiseaseprogression,cholestasisgivesrisetocirrhosisandcommoncomplicationsof
cirrhosisleadingtodeath(varices,encephalopathy)
AlkPhosmaybeonlyindicatorandtherearenoautoantibodies
Strongassociationwithulcerativecolitis(fromGI)

PrimarySclerosingCholangitis.Bileductwith PrimaryBiliaryCirrhosis.Lymphocytesand SecondaryBiliaryCirrhosis.Yellowgreenliverfrom
onionskinningfibrosisofPCS plasmacellsfillabiletractwhileagranuloma bilestainingaftersecondarybiliaryobstruction.Bile
formstothebileduct(arrow) lakesarelikelypresentaswellasafuturefibrosis
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WedidnotcoverCIRCULATORYDISIRDERS(917/464)PREGNANCY(920/466)orORGAN
TRANSPLANTATION(921/467)sothosesubjectswillnotbecoveredhereinthisguide.

NODULESANDTUMORS(BigRobbins922,Baby468)

NodularHyperplasias
Scar,Pale,Normal
FocalNodularHyperplasia
o Spontaneousmasslesionfoundinyoungtomiddleagedfemales(morethanmales)
o Itiswelldemarcatedbutpoorlyencapsulatednodule,andispalerthannormalliver
o Hasacentralstellatefibrosiswithsurroundingnormalparenchyma
NodularRegenerativeHyperplasia(notdiscussedinclass)

FocalNodularHyperplasia. o DiffuseNodularTransformationoftheliverwithoutfibrosis
Thelargenodulehasa
o AssociatedwithVasculitidesandsolidorgantransplants(especiallykidney)
centerfibroticscar(white)
andispalerthannormal o Mayleadtoportalhypertension
liver
BenignNeoplasms

CavernousHemangioma,akaHemangioma
o MostCommonbenignlesionoftheliver
o Consistsofwellcircumscribedlesionsofendotheliallinedvascularchannels
o Appearasdeepred,softnodulesbeneaththecapsularsurface
o Thesearenotmetastatictumorsanddonotrequirebiopsy
CavernousHemangioma.
GrossimageofSoft,red, LivercellAdenoma Adenoma.Normallooking
strawberryappearance o Benignneoplasmsarisingfromhepatocytes hepatocyteswithoutbile
o Occursinwomenusingthepill/pregnant;goawayonceshestopspill/baby ducts
o MaybemistakenforHCCormayrupture/bleedduringpregnancy(anemergency)
o Usuallywelldemarcatedbutpoorlyencapsulatedtumorswithfewbiletractsbutmany
arteriesandveins;itlookslikenormalliverwithoutthevessels

MalignantNeoplasms

Metastasis
o Likethelungs,theliverhasahighbloodflowandsoisvulnerabletometastasis
o Themostcommonsitesoforiginarethecolon,lung,andbreast
Hepatoblastoma
o Mostcommontumorofchildhood,fatalinoneyearifnotresected
o EpithelialType=fetalorembryonalcellsformingasemblanceofliver
o MixedEpithelial+Mesenchymal=poorlydifferentiatedmassofmesenchyme
Hepatoblastoma.Hasa
centralscar,butisalarge o Anelevatedfetoprotein(AFP)inachildisagoodtipoff
Angiosarcoma
nodule(1/2theliver)andis
thesamecolorasliver
o Resembleangiosarcomasoccurringanywhere
o Areassociatedwithcarcinogenicexposure(vinylchloride,arsenic)whenintheliver
o Extremelypoorprognosiswithdeathoccurringin<1year

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Tumor(pale)
Cholangiosarcoma
o TumorofbothoreithertheIntrahepaticorExtrahepaticbiliarytree
o RareintheUS,commoninAsia
Thorotrast,anobsoletecontrastdyeforbiliaryradiographycausedit
ChronicInflammationfromPrimarySclerosingCholangitis(US),Ulcerative
Tumorwithmanymetastases
Cholangitis(US),orOpisthorcisSinensisInfection(liverfluke,Asia)
o CarryadismalprognosisfarworsethanHCC
o Diagnosisisusuallylate,andpresentswithbileobstructionandjaundice
o Surgeryistheonlytreatmentoption,thoughisusuallypalliative
o Thereisnobileproductioninthetumor,anditresemblesductsofthebiletract
Ductalstructuresarepresent o SerumCEAandSerumCA199aremarkersfordisease
withinscleroticstroma
HepatocellularCarcinomaitsamalignanttumor,butreallyimportant,soitgetsitsownheading

Pathogenesis
o ChronicInflammationforceshepatocytesintoacycleofnecrosisandregeneration;
mitoticactivityforregeneration=riskoftransformation
o HepBisthemostprevalentcauseworldwidepresentingwithorwithoutcirrhosis
MostprevalentinAsia,whereHepBinfectionsareabundant
HepBintegratesintohostDNA,andHepXproteinfacilitatestransformation
HepDcoinfectionexacerbatesHCC
Morphology
o ImagingStudiesofURQmass+AFP=pathognomonic(biopsyisnotrequired)
o HCCisusuallypalerthanthenormalliversurroundingit
o Propensityforgrowthintovascularchannels
o InwelldifferentiatedHCChepatocytesretainsomesemblanceofhepaticarchitecture
Large, Pale tumor within a o InpoorlydifferentiatedHCCtherearePleomorphicgiantcells,anaplasia,and
normal liver in an adult.
cytoplasmicinclusionsthatresembleMallorybodies
Clinical
o Difficulttospotaspatientsymptomsarenondescriptormaskedbycirrhosis
o HepatitisSx(anorexia,malaise,ABDpain,weightloss)andLiverFailureSx
(hemorrhoids,esophagealvarices)canbevariablyfound
o ElevatedLevelsoffetoprotein(AFP)isastrongindication,esp.withsymptoms
o Whiletheydoinvadevasculature(andmaygrowoutfromtheliverintotheIVCor
Welldifferentiatedtumorcells portalvein)thesetumorsrarelymetastasizeoutsidetheliver
formingnests,somewitha
centrallumen,onefilledwith o Surgeryistheonlytreatmentoption:resectionandtransplantoftenresultin
bile(arrow) reinfection(withHepB)orinrecurrenceoftumor
FibrolamellarHCC
o Occurinyoungpeoplewithnormalliversandcarryagoodprognosis
o Mentionedinlecture,doesntshowupinreviewbooks/Kaplan

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DISEASESOFTHEGALLBLADER(BigRobbins928,BabyRobbins471)

Cholelithiasis=Gallstones(cholesterolorpigmentformedWITHINthegallbladder)

CholesterolStones
o Etiology=Forty,Fat,andFertile

NativeAmericans White>Black Estrogen(thepillandbeingfemale

Age Hypercholesteremia Inbornerrorsofmetabolismthatbilesaltsecretion
GallbladderStasis(Pregnancy) Obesityandrapidweightloss DevelopedCountries(eatmore)
o Pathogenesis
Normally,cholesterolissolubilizedbybilesaltsandlecithin
Whensupersaturated,cholesterolnucleatesintocrystals,formingstones
4Simultaneousdefectsarerequired
(1) Bileissupersaturatedwithcholesterol(forwhateverreason)
(2) Gallbladderhypomotilityallowscongregationandnucleation

Allthegreenish,yellowthings,of
(3) CholesterolNucleationisaccelerated(calciumsalts,changein[protein])
varioussize.Theyareyellowonthe (4) MucousHypersecretiontrapsthecrystals,allowingthemtoformstones
outside,blackgreenontheinsideo Morphology

PureCholesterolStone(rare)appearpaleyellowandareradiolucent
Moststonesarecomposedofcholesterol,pigment,calciumcarbonate,etc.,
thoughonly1020%becomeradioopaque
PigmentStones
o Etiology=

Asian>Western Rural>Urban CysticFibrosis(Pancreatic)

ChronicHemolyticSyndromes BiliaryTractInfection IlealDisease(resectionorbypass)
(productionofbilirubin)
o Pathogenesis
Insolublecalciumsalts+unconjugatedbilirubinandotherinorganicsalts
Unconjugatedbilirubininthegallbladderrequiresconjugatedbilirubintobe
deconjugatedwithinthelumenwhichoccurstoaverysmallextentnaturally
IntenseHemolysiswillconcentrationofunconjugatedbilirubin(black)
BiliaryinfectionbyE.Coli,Ascaris,orLiverFlukesaremorelikely(brown)
Smallblackrabbitturdsinsideo Morphology
thegallbladder
BlackStonescomefromasterilegallbladderandareoftenradioopaque(75%)
BrownStonescomefromaninfectedgallbladderandareusuallyradiolucent
Clinical(sameforbothtypes)
o Maybeasymptomaticfordecades
o SymptomsareUpperRightQuadrant,ColickyAbdominalPain(akaCholecystitis)
o Obstructionmayresult,riskofinfectionorobstructionpreventingtheeliminationof
bilirubinorbilesalts,termedgallstoneileus
o Dependingonlocationofstone,itcancausebiliarytractobstruction(distalbiliarytree),
acutepancreatitis(sphincterofoddi),orcholecystitis(neckofthegallbladder)

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Cholecystitis(BigRobbins931,BabyRobbins472)

Definition
o Inflammationofthegallbladderforanyreasonthatmaybeacuteorchronic

AcuteCholecystitis

Pathogenesis
o Maybecalculous(aka,involvesgallstones)
Mostcommoncomplicationofcholelithiasis,precipitated90%byductocclusion
Obstruction=Flow=Stagnantlethicin=aberrantenzymeactivityandthe
generationoftoxiclysolethicin=destructionofmucosallayeranddirect
detergentactiononwallofgallbladder
o Maybeacalculous(aka,somethingotherthanobstructionandgallstones)
Resultingfromischemia(cysticarteryisanendarterywithoutcollaterals)
BloodFlow/Shock/Hypoperfusion
BacterialContamination,MassEffectofaTumor
Morphology
o Isthesameforcalculousvs.acalculous(exceptforthepresenceofstones,ofcourse)
o Gallbladderisenlarged,tense,andred(engorged)orblotchy(hemorrhage)
o Serosaislayeredwithfibrin
o Lumenmaycontainfibrin,pus,orhemorrhage
Iforganistransformedgreenblack,itiscalledgangrenouscholecystitis
Clinical
Enlarged,tense,andred.
Shinycoat(serosal)is
o UpperRightQuadrantPain,LowGradeFever,Nausea+Vomiting,Tachycardia
interruptedbybrief o AbdominalTendernesswithpositiveMurphysSign,freeofjaundice(usually)
periodsoffibrin. Deeppalpationofgallbladderwillterminateinspiration(becauseofpain)
Hemorrhagepresenton
thetopright
o Maybeanimmediatemedicalemergencyormayresolvewithoutintervention
o Most(90%)calculouscholecystitiswillrecur
o Potentialcomplicationsincludeperforation/peritonitis,superinfection/cholangitisand
fistulaformationtotheduodenum

ChronicCholecystitis

Pathogenesis
o Maybetheresultoffrequentacuteattacksormayoccurwithoutantecedentsymptom
o Samepopulation,riskfactors,andgenerationasacute
Morphology
o Wallsarethickened,fibrosisisoftenapparent,calledporcelaingallbladder
o Lumenmayormaynothavegallstones(butitoftendoes)
o LipidLadenmacrophages(cholesterosis)iscommon
Thickenedwalls(white) o MucosaloutpouchingsintothelumenarecalledRakitanskyAschoffSinuses
withgallstonesinside.
Clinical
o SameasAcuteCholecystitis

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DISEASESOFTHEGALLBLADER(BigRobbins933,BabyRobbins473)

Choldeocholithiasis

Presenceofstoneswithinthebileductortree(opposedtoinsidethegallbladderproper)
U.S.=cholesterolstonesfromgallbladder;Asia=pigmentstonesformedinbiliarytree
Causessymptomsofobstruction

Cholangitis/AscendingCholangitis

BacterialInfectionofthebileducts,oftencausedbycholdeocholithiasis
UsuallyaresultofascendinginfectionfromthesphincterofOddi
Commonlycausedbygramnegativeaerobes=E.Coli,Klebsiella,Clostridium,Bacteroides
Fever,shakingchills,abdominalpain,jaundice,intermittentobstructivesymptoms

BiliaryAtresia

CompleteObstructionofbiliarylumenwithinfirst3monthsoflifeaccountingfor1/3of
infantilecholestasis
Causedbyamultihitprocessthatinducesfetalform(biliarytreeneverdevelops)orthemore
commonperinatalform(destroyed@birth)
Thereisfibrosisandstrictureofcommonbileducts
Ifbelowtheliver,itisamendabletosurgery
Patientsgrow,eat,andpoopnormallyatfirst,thenbegintogetacholicstoolsasthedisease
progresses;deathiswithintwoyearsofbirth

TUMORSOFTHEGALLBLADDER(BigRobbins934,BabyRobbins474)

CarcinomaoftheGallbladder

Pathogenesis
o Occursmorecommonlyinfemalesinthe7thdecadeoflife
o Oftenfoundwithchronicgallstones(US)orPyogenic/parasiticinfections(Asia)
ChronicInflammationfromanycausethoughttoRisk
o Evenwithresection,5yearsurvivalis<1%
Morphology
o TwoTypes
Infiltrating=morecommon,diffuselygrowsaroundandintothegallbladder,
mayulcerate,causingfistulaintotheGItract
Exophytic=growsintothelumenandinvadesdeeply.CauliFlowerStalkin
thelumenmaybehemorrhagic,necrotic,orulcerative
o Mostareadenocarcinomawithaselectfewhavingsqaumouscellcharacteristics
Clinical
o Bythetimethesearefoundtheyhavealreadymetastasized/seededlocally
o Symptomsareinsidiousandindistinguishablefromcholelithiasis
o Luckypatientsfindtheseonincidentalgallstoneremoval

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CarcinomaofExtrahepaticBileDucts

Rare,insidioustumorspresentingsimilartolatestagepancreatictumors(painlessjaundice)
RiskwithprimarySclerosingcholangitisandcysticliverdisease
Riverflukes(clinorchissenesis)inAsiagreatlyrisk
Partialorcompleteobstructionofbileductsrapidlyproducesjaundice;theseareusuallyfound
early,assmall,grey,firmmassesofthebiliarywall
Thereisoftenabundantfibrousstroma
TheseareidenticaltoIntrahepaticbileductcancer,calledCholangiosarcoma

Disease
HepaticFailure
Cirrhosis
PortalHypertension
Jaundice
AlcoholicLiverDisease
AST>ALTby1.5xormoreis
pathognomonic
NonalcoholicFattyLiver
Hemachromatosis
Wilsons
1AntiTrypsinDeficiency
PrimarySclerosingCholangitis
AutoimmuneLiverDisease
DrugInduced
MAJORDISEASESOFTHELIVER
Character
Consequenceoflongterminflammation(cirrhosis)orfulminantnecrosis
ResultsinClottingFactors=PTT,Albumin=Ascites,Portalhypertension(see
below),Estrogen=Gynecomastia,Ammonia=hepaticencephalopathy,
Hepatorenalsyndrome,fetorhepatus
IslandsofRegeneratingParenchyma amongstBroadBandsofFibrosis
Isendstagefibroticdiseaseofmultipleorigins
Nodular(micro=alcohol,macro=virus),shrunken,discoloredappearanceongross
Consequenceofimpairedbloodflowthroughliverwhichcanbeprehepatic
(hypoperfusion),Posthepatic(portalveinthrombosis),orIntrahepatic(cirrhosis)
ProducesPortosystemicshunts=EsophagealVarices,Hemorrhoids,CaputMedusa
Causessplenomegalyandincreaseshydrostaticpressureproducingascites
Definedasturningtheskinyellow,mayalsoinvolvetheeyes(scleralicterus)
Consequenceofelevatedbilirubin;determineifunconjugatedorconjugated!
CausedbyprepostorIntrahepaticmechanisms;hemolysis(delivery),
conjugation(geneticdefects),bileflow(obstruction)
Progressivediseasecausedbychronicorsevereacutealcoholconsumption.
Progressesfromsteatosis(lipidvacuolization)throughfibrosistocirrhosis
LookforMallorybodies,BallooningDegenerationandaNeutrophilicreaction
Unlessfibrotic,changesarereversiblewithabstinencefromalcohol
Steatosisintheabsenceofalcoholconsumption
Occurringinobesediabeticswithderangementsinfatutilization
FatPeoplegetFatLivers
AutosomalrecessiveC282Ymutation whichdisablestheweveenoughironsignal
Defaultofenterocytesistobringinmoreironwhichcannotbeeliminated
Irondepositsintheliver(brownliver),pancreas(diabetes)andtheskin(bronzing)
Treatmentisphlebotomyorlivertransplant
AutosomalRecessiveDisorderinvolvingcopperextrudingprotein
Livercannotexcretecopperfrombody,ceruplasminisoverwhelmedasblood[Cu]rises
Depositsintheliver,thebrain(basalganglia)andeye(KayserFleisherrings)
WillfindHepaticCu,UrineCu,SerumCeruplasmin(SerumCuisuseless)
AutosomalRecessivedisorderinvolvingthemisfoldingof1AT
IntracellularPASPositiveEosinophilicGranulesinHepatocytes=pathognomonic
PiMM(homozygous)isnormalPiZZ(homozygous)isworstPiZM(heterozygous)mid
Increasedriskofemphysema(dontsmoke)andcirrhosis(dontdrink)
SegmentalConcentricInflammationofthebiliarytreewithanunknowncause
AssociatedwithUlcerativeColitis,increasesriskforCarcinomaofBileDucts
Diseaseoffemales withANAandSMAautoantibodiesinblood
Respondswelltosteroids
Drugscancauseliverfailure

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 PathGILiverBiliaryExocrinePancreas

TYPESOFBILIRUBINDISEASES JAUNDICE
Disease Character
ErythroblastosisFetalis RhmomhasasecondRh+ baby,momsantibodiesdestroybabysRBCs
(Hemolysis) Hemolysisreleasesbilirubin,babysliverisntreadyforit,baby=jaundice
Increasedbilirubin=jaundice;modelforanyhemolyticanemia
NeonatalJaundice Neonatesrequire2weekstoachieveconjugationcapacity
NeonatalJaundiceandmildhyperbilirubinemiaisok;physiologic
CriglerNajjar1 AutosomalRecessive,Unconjugated,FatalwithoutTransplant
AbsentUTGconjugationprotein
Gilbert AutosomalRecessive,Unconjugated,NormalLife withsporadicasymptomaticjaundice
MutatedPromoter(TATA)forUTGconjugationprotein,reducedexpression
DubinJohnson AutosomalRecessive,Conjugated,NormalLife andaBlackLiver
MutatedbileCannaliculartransportprotein;mostcommonlytestedUSMLE
Rotor TheexactsamethingasDubinJohnson(Conjugated),excepttheliverisntblack
BiliaryTractObstruction Bilirubingetsintoliver,conjugated,can betransportedbutFlow=Excretion
(PSC,Stones,Cancer) ConjugatedBilirubin=claycoloredstools,darkurine,nokernicterus
COMPARISONOFBILIRUBINTYPES
Conjugated Unconjugated
WaterSoluble,cannotpenetrateBBB,excretedinUrine WaterInsoluble,CanpenetrateBBB,notexcretedinUrine
Doesnotcausekernicterus CausesKernicterus,isfatal
Turnsurineadarkbrown,skin/eyesjaundice Nochangeinurine,butskin/eyesarejaundiced

INFECTIOUSHEPATITIS
Disease Character
HepA FecalOralRoutefortransmission
CausesOnlyAcuteHepatitis
RNAvirus,vaccineavailable
HepB IVDrugsandSexualContact fortransmission (adults)orverticaltransmission(children)
CausesMostlyAcutebutmaycauseChronicHepatitis(immunocompromised=chronic)
IncompleteDNAvirus,producesHBsAg,HBeAg,HBcAg,HepXprotein,vaccineavailable
Serology:HBsAgIgG=Immunity,HBsAgIgM=Acute/Active,HBcAgIgG+HBsAg=chronic
Ifchronic,riskforHepatocellularCarcinoma(HepX)andsmallriskforcirrhosis
HepC IVDrugsandSexualContact fortransmission (adults)orposttransfusion(anemic)
CausesMostlyChronicbutmaycauseAcuteHepatitis;
RNAvirustransmittedthroughblood
Usuallyprogressestocirrhosis,smallriskforHCC
HepD IVDrugsandSexualContact for transmission
Cannotinfecthepatocytesonitsown,requiresHebBcoinfection
WorseningHepBinfection(hepatitisandHCC)orproducesfulminanthepatitis(superinfection)
Bacterial, Formabscesses,usuallyacquiredoutsideofUS
Fungal, Commonpyogenicinfections=sameforcholangitis=GIflora(E.Coli,Klebsiella,etc)
Parasite Amebiasis(entamoebahistolytica)andSchistosomiasiscommonparasites
Schistomsa CausesPortalHypertension,otherspeciesmaycausebladdercancer
Clinorchis RiskofCholangiosarcoma,causesbiliaryobstruction
Senensis

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 PathGILiverBiliaryExocrinePancreas

Disease
CholesterolCholelithiasis
Fat,Forty,Fertile,Female RiskwithObesity,Pregnancy,OralContraception,Female,NativeAmerican
PigmentCholelithiasis
Cholestasis
Cholangitis
BiliaryAtresia
Primarybiliarycirrhosis
DISEASESOFTHEGALLBLADDER
Character
CholesterolStonesareyelloworgreen,formedfromcholesterolcalciumsalts
Maycausebiliaryobstruction,cholangitis,jaundice
PigmentStonesareblackandmadefromunconjugatedbilirubin
RiskwithHemolyticAnemia,LiverFlukes
Maycausejaundice,cholangitis,biliaryobstruction
Stasisofthebiliarytreemaybecausedbyintrahepaticmechanisms(Gilberts
MRP2)whichisnotamendabletosurgery,orbyextrahepaticmechanisms
(obstruction,cancer,stones,infection)isamendabletosurgery
BacterialInfectionmostcommonlycomingfromtheGItractandascending
Commonorganisms=E.Coli,Klebsiella,andBacteroides
Biliaryductsdonotform,patientcannoteliminatedbileorcholesterol
Amendabletosurgeryifoutsidetheliver
Autoimmunediseaseaffectingthegallbladdercausinglymphocyticgranulomas
FemalepreponderancewiththepresenceofAntimitochondrialAntibodies(AMA)
PatientpresentswithXanthomas,Pruritis,andJaundice/Icterus

TUMORSOFTHELIVERANDGALLBLADDER
Disease Character
FocalNodular Benignnodulargrowththatisnonneoplastic
Hyperplasia Hasapalercolorandacentralfibroticscar
Cavernous BenignneoplasticgrowthofvasculartissuerelatedtoCCl4 Exposure
Hemangioma Isseenasdarkerred,mushierspotsontheliver
LivercellAdenoma BenignNeoplasticgrowth ofhepatocytesassociatedwithhighestrogen
Femaleswhoarepregnantoronoralcontraceptivesareatrisk
Cessationofestrogensource=sizeandgrowthofneoplasm
Metastasis Mostcommontumoroftheliver,commonsitesarefromGI/Colon,Breast,Skin
Highbloodflow(portalveinandhepaticartery)predisposeformetastasis
Presentasmultiplediffusesmalllesionsintheliver
Hepatoblastoma Tumorofchildhood,consistingoffetal(epithelial)ormesenchymal(mixed)tissue
Largenodulargrowththatisthesamecolorastheliverandhascentralscar
IndicatedbyanelevatedAFPinakid(AFPinadult=HCC)
Angiosarcomaof TerriblePrognosistumorsimilartoangiosarcomasanywhere
Liver RiskwithexposuretoVinylChloride
Hepatocellular HighestyieldtumorfortheGIsection
Carcinoma(HCC) Causedbychronicinflammatorydiseases(cirrhosis,HepBinfections)andare
commoninAsia(HepB)orinUSalcoholics(cirrhosis)
Lovestoinvadebloodvesselsthoughitrarelymetastasizesoutsidetheliver
IndicatedbyadultlivermasswithanelevatedAlphaFetoProtein(AFP)
Transplantmaynotbecurative(reinfectionwithHepB)
FibrolamellarHCC VariantofHepatocellularCarcinomathatoccursinyoungeradultsandhasafavorable
prognosis.Extremelylowyield(havenotencountereditoutsideofclass)
Carcinomaofthe Causebychronicinflammatorydiseaseofthegallbladder(ClinorchisorCholecystitis)
Gallbladder Bearsaterribleprognosiswithmetastasisandseedingfoundatdiagnosis
Indicatedbyapalpable,painlessgallbladder
Carcinomaofthe IfIntrahepatic,carcinomaofthebileductgetsaspecialname=Cholangiosarcoma
BileDuctsand Carriesadismalprognosis(<5%1yearsurvival)presentingwithapainlessjaundice
Cholangiosarcoma Infact,painlessjaundiceisalmostpathognomonicforcarcinoma(bileductorpancreas)

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 PathGILiverBiliaryExocrinePancreas

LABORATORYMARKERSOFLIVERFUNCTION
EnzymeorMarker WithInjuryor Rationale
Dysfunction
HepatocyteInjury
AspartateAminoTransferase(AST) Allthreearemarkersforinjury,enzymescontainedwithin
AlanineAminoTransferase(ALT) hepatocytes.WithHepatocellularnecrosisorapoptosis,enzymesare
LactateDehydrogenase(LDH) released,soserumlevelsincrease,amarkerforinjury.
BiliaryFunction
SerumBilirubin
Total(everything) Ifunconjugated,riskforkernicterus;lipidsolubleunconjugated
canpenetrateBB,cannotbeexcretedrenallyandisneurotoxic
Direct(conjugated) Ifconjugated,mostlikelysecretionmutationorbiliaryobstruction.
ConjugatedBilirubinnontoxicandexcretedinurine
SerumBileAcid Bileacidsaremadeintheliver,secreted,andrecirculatedthrough
enterohepaticcirculation.Increasedlevelsmeansbiliaryobstruction.
Causespruritis,bilelakesinliverwillbeseen
SerumAlkalinePhosphatase Containedinbiliarycells,releasedduringcholestasis,asbileacids
destroyliningofbiliarywalls,markerofbiliarydamage
HepatocyteFunction
Albumin Thelivermakesalbumin.Iftheliverisntworking,itwontmake
albumin.Thisincreasesriskforascitesandedema
ProthrombinTime Livermakesclottingfactors.Iftheliverisntworking,itwontmake
(PTandaPTT) theclottingfactors,soyouwontclot,andclottingtimeincreases
Ammonia Theliverprocessaminoacids(ureacycle).Iftheliverisntworking,it
buildsupammonia,whichcancausehepaticencephalopathy

PANCREASTUTORIALSESSION(wasntreading,butknowtheseexist)
Disease Character
Agenesis Nopancreasforms
Incompatiblewithlife
Pancreas Twotubesformtodeliverexocrinejuices.Inthiscasethesmalleronecarriesmostofthejuices,whilethe
Divisum largerone(ampulaofVater)carrieslittleofthejuice
Annular Abandlikeringofpancreasformsaroundthe2nd partoftheduodenum,
Pancreas Presentslaterinchildhoodlifewithvomitinguponeating
Ectopic Pancreasgrowswhereitshouldnt,alwaysneartoitsstartingpoint
Pancreas Stomach,Duodenum,jejunum,MeckelsDiverticula,Ileum
Acute Reversiblelesionsofinflammation,fatnecrosisandsaponification causedbyAlcohol
Pancreatitis Causedalsobyobstructionofpancreaticduct(ClinorchisSinensisorGallstoneatSphincterofOddi)
Protectedenzymesgetstuckandactivateinpancreas=autodigestion,Representsamedicalemergency
Increasedserumamylaseandincreasedserumlipasewithsharpepigastricpainradiatingtotheback
Allowpancreastorestafteranacuteepisode=totaldietaryrestriction
Chronic Inrepeatedacutepancreatitis,alcoholism mostcommon,ortheformationofconcretionsinexocrineducts
Pancreatitis Resultsinfibrosisandshrinkageofthepancreaswithlossoffunction
Presentswithabdominalpain,mildfever,mildelevationsofamylase,andmalabsorption(A,D,E,andK)
Zollinger Gastrinsecretingtumorofthepancreas
Ellison Causesupregulationofacidsecretioninthestomach
Syndrome PresentswithulcersintractabletoH.pyloritreatment
Insulinoma Insulinsecretingtumorofthepancreas,Hypoglycemia,coma,anddeathcanresult
Causesreleaseofinsulin(testforcpeptidetoconfirmendogenousproduction)
ItstheonlyIslettumorwelearnedabout,youdonthavetoknowaboutotherIsletTumors

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 PathGILiverBiliaryExocrinePancreas

TUMORSOFTHEGITRACT
Disease Location Character
Barretts Esophagus ProtectivemetaplasiatocolumnarepitheliumwithgobletcellsinresponsetoGERD
Isprecancerous,inducingdysplasiaandeventualadenocarcinoma(3040xrisk)
TreatmentwithPPIsmayreversedysplasiaandmetaplasiapriortocarcinoma
Adenocarcinoma Esophagus LeadingesophagealtumorintheUnitedStates
Dysphagiatosolidfoodthenliquids,bleeding,andweightLoss(sameassqaumouscell)
UsuallyfollowsBarrettsEsophagus,foundinthelowerthirdofesophagus
SqaumousCell Esophagus Leadingesophagealtumorworldwide
Carcinoma Dysphagiatosolidfoodthenliquids,bleeding,andweightLoss(sameasadenocarcinoma)
Resemblesothersqaumouscellcarcinomas,maybekeratinized,upperthirdofesophagus
GastricCarcinoma Stomach MostcommonsitesareAntrum(50%),LesserCurvature(40%)=H.PyloriInfections
Asymptomaticuntilsevere,grossshowslinitisplastica(thickeningofmucosallayer)
IntestinalTypeshowsintestinalmetaplasiaandisassociatedwithH.Pylori
DiffuseTypeshowssignetcellringsandispoorlydifferentiated
KrukenburgsTumortotheovaries,VirchowsNodeneartheclavicle
MALTomas Stomach NonHodgkinslymphomaofthestomach,mostH.Pyloriassociatedcancer
WillregresswithantibioticsifcausedbyH.Pylori
StromalTumors Stomach Raretumoroftheinterconnectivetissueofthestomach(theStroma)
CausedbyanoveractivityofTyrosineKinase,treatedwithGleevac/Imatinib
Adenomatous Colon Benigngrowthsthatmaybecomecancerous
Polyps Areeithersessile(withoutastalk,malignant)orpedunculated(withastalk,benign)
Areeithervillous(fingerlikeprojections,malignant)ortubular(normalcolon,benign)
Occultbloodinstoolleadstoascope,polypsarefoundandharvested
Familial Colon AutosomalDominantmutationoftheAPCgenecausing100s1000sofpolyps
Adenomatous EntireColonisfullofpolyps,chancesthatonewillbecomedysplastic(cancerous)
Polyposis(FAP) Recommendedprophylacticcolectomy,usuallydiagnosedinteens/twenties
Gardner Colon AnFAPvariantwithosteomasofthejaw,fibromatosisoftheabdomenandbenignepithelial
inclusioncystsintheskin(verylowyield)
Turcot Colon RarevariantofFAPthatisautosomalrecessive;TURcots=TURban=Brain
1000sofpolypsPLUSindependentbraintumors(usuallymedulloblastoma)
HNCPP Colon AutosomalRecessiveMutationoftheDNAMismatchRepairGenes
Thesepatientshavenopolypsbutgetcoloncanceranyway
Riskforovarianandendometrialtumors
PeutzJeghers Colon PatientusuallypresentswithDarkSpotsonthelips(Hyperpigmentedlesions)
Endoscopyrevealshamartomous(benign)polypsofthesmallintestine
LookforcancerssomewhereelseotherthantheGItract(lung,skin,liver)
Colonic Colon #3CancerinAmerica,#3CancerKillerinAmerica,causedbyoneofmanymutations
Adenocarcinoma RightSidedTumorsaremoredangerous
Stoolissoft,sothereisnoobstructivepresentationtotheExophyticlesion
Onlyclueishemeoccultbloodinstool(GUIACtest)promptedbyanemia
LeftSidedTumorsaremorenoticeable
Causesanapkinringstricture,presentingwithobstruction
Bowelhabitsshowalternatingconstipationanddiarrhea
Bariumenemashowsanapplecorelesion
Hemeoccultbloodisalsopositive(GUIAC)
Bothtendtometastasizetotheliver
Carcinoid Colon MayoccurintheLungandAdrenalgland(whichareimmediatelysymptomatic)
Thosearisinginthecolonmustfirstmetastasizetothelivertobecomesymptomatic
Firstpasslivereffectneutralizesserotonin;oncemetastasized,liverdoesnotclear
Causescramping,flushing,diarrhea,andfibrosisoftheheartvalves(rightifcolon)
Lookfor5HIAAintheurine,ametaboliteofserotonin(5HT)

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DISESASESOFTHEESOPHAGUS
Disease Character
Fistula Connectionbetweenanytwotubesusuallyoccurringwithatresiaandbetweentheesophagusandtrachea
Presentswithaspirationpneumoniaandpolyhydramnios;Amendabletosurgery
Atresia Esophagusendsinablindpouch.Commonproximalatresiawithdistalfistulatothetrachea
Webs Projectionsofmucosalepitheliumintothelumenoftheesophagus;cantrapfood=malodorousbreath
WhenassociatedwithirondeficiencyanemiaitiscalledPlummerVinsonSyndromeandRiskforSCC
Achalasia FailureoftheLEStorelax,preventingfoodfromenteringthestomach,Stentorresectioniscurative
Presentswithdysphagiathatisusuallynotprogressiveandwithoutweightloss
CausedbyalossofganglionicneuronsoftheLES;lookforbirdsbeakappearanceofesophagus
Stricture GERD,failureofneuralcrestmigration, otherinsult(LyeIngestion,EsophagealChagas,Toxins) damage;
Repairleadstointraluminalfibrosisandnarrowingofthelumen
Presentswithprogressivedysphagiawithoutweightloss(absenceofweightlossdifferentiatesfromcancer)
Mallory Associatedwithsevereretchingfoundcommonlyinalcoholicsandbulimics
Weiss Arelongitudinaltearsofthemucosausuallyfoundatthegastroesophagealjunction
Tears CauseamildupperGIbleedthatwillhealspontaneouslywithcessationofretching;nonlifethreatening
Esophageal Associatedwithliverfailureandsubsequentportalhypertension(cirrhosis,Schistosomiasis)
Varices Portocavalshuntsformedthroughanus(hemorrhoids),abdomen(caputmedusa)andesophagus(varices)
Aretortuousdistendedveinsoftheesophagusthatarepronetorupture(especiallywithvomiting)
ProducesalifethreateningupperGIbleedwithhematemesisandmelena.Surgicalinterventionrequired
GERD GastroesophagealRefluxDiseasecausedbylowtoneoftheLES allowingstomachcontentstoreflux
Enhancedbyconsumptionoffat(slowsgastricemptying),chocolate/alcohol/smoking(relaxessphincter)
Causesaburningpainintheepigastricregionasstomachaciddamagesesophagus
Producesabasalzonehyperplasia(germcellactivitytoreplacedamagedtissue)orsimplehyperemia
Lastsfor1020yearsifuntreated,metaplasticBarrettsEsophagusorstricturesetsin
Barretts Aproductoflongstanding,untreatedGERD; it is a premalignant condition
Esophagus Resultsinametaplasticchangetocolumnarepitheliumwithgobletcells
Appearsvelvetysalmoncoloredepitheliumonendoscopy
BurningofGERDprogressivelydisappearswithouttreatment(protective,precancerouschange)

DISEASESOFTHESTOMACH
Disease Character
Diaphragmatic Congenitalweakeningtheindiaphragm thatallowsforthestomachandintestinestoprotrude
Hernia Thiscancausepulmonaryhypoplasiaiftheherniationissignificant(usuallyontheleftposterior)
HiatalHernia Maybecongenitaloracquired
SlidingHiatalHerniaiswheretheFundicstomachgoesupthroughtheholewheretheesophagusis
ThisriskforGERD,almostnoriskforincarcerationorstrangulation
ParaesophagealHiatalHerniaiswhereanotherpartofthestomachgoesthroughthediaphragm
ThisriskforIncarcerationorstrangulationofstomach,littleriskforGERD
Pyloric Acongenitalstenosisorblockageofthepyloricvalve in an infant, myotomyiscurative
Stenosis Presentswithnonbiliaryprojectilevomitingaftereatingandapalpableolivelikemassabdomen
Menetriers Diseaseofmiddleagedmenthatcausesanincreasedthicknessofthemucosabyproliferatingneckcells,
Disease replacingchiefandparietal,causingacidsecretionbutwithanincreasedriskforgastriccarcinoma
Itisaproteinlosingenteropathy,whichmeansedemaandascitesNOTrelatedtotheliver
Zollinger AGastrinsecretingpancreatictumor;Gastrin activatesproliferationofandsecretionfromparietalcells
Ellison RiskforGERDandPepticUlcer(fromacid)andthickeningofmucosa/carcinoma
Acute Acute(Neutrophilic)inflammationofthegastricmucosa,a resultofthefailureofmucosalbarrier
Gastritis (NSAIDs,Ischemia,DuodenalRegurgitation)orincreaseinacidsecretion(ZollingerEllison)
Maypresentwitherosion(confinedtomucosalepithelium),ulceration(deeperlayers),orhemorrhage

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 PathGILiverBiliaryExocrinePancreas

PresentsasanUpperGIbleed(melena,possiblehematemesis,oranepigastricpain)
Chronic Chronic(lymphocytic)inflammationofthegastricmucosaresulting inatrophyofgastricfolds
Gastritis TypeA=fundictype,andautoimmunedisordertoparietalcellsandIntrinsicFactor=PerniciousAnemia
TypeB=antraltype,andiscausedbyHPyloriInfections(pylorus>antrum>greatercurvature>cardia)
Ulcersin Ulcersarebenign(noncancerous)punchedoutholesinthegastricmucosawithwelldefinedborders
General Riskfactorsincluedsmoking,NSAIDs,Aspirin,andHPyloriinfections
AntibioticsandCessationofthebadhabitsisnormallycurative
GastricUlcers AcuteUlcersareaproblemoftheICU,andexacerbationofacutegastritis.Theyaretermedstressulcers
Stressmeansburns/trauma(CurlingsUlcers),raisedICP(CushingsUlcer),sepsis,orhypotension
ChronicUlcersareaproblemofchronicgastritis,associatedwithHPylori75%ofthetime
Causeaburningorgnawingepigastricpainthatismadeworsebyeating
Affectsthepylorus/antrum(50%),greatercurvature(40%),cardia(5%)esophagus(5%)
Duodenal Achroniculceriscausedbyeither ZollingerEllison and H.Pylori,affectingtheproximalduodenum
Ulcers Producesaburningorgnawingepigastricpainthatisalleviatedbyeatingandstartshoursafterameal

DISEASESOFTHECOLONANDSMALLINTESTINE
Disease Character
Volvulus Loopingofthebowelarounditselfleadingtobothobstructionandinfarctionofbowel(elderly)
IntussusceptionTelescopingofthebowelintoitselfleadingtobothobstructionandinfarctionofbowel(infants)
Incarcerated Aherniaisaloopofbowelpenetratingamuscularwall
Hernia Whenthebowelgoesthrough,themusclemaycontract,trappingtheboweloutside.
Incarcerationcausesobstruction,Strangulationcausesinfarct,thoughtermsmaybeinterchangeable
Herschbrungs Acongenitaldisorderwherebyneuralcrestcellsfailtomigrateandthecolonlacksautonomicganglia
Disease Theaffectedsitelooksnormal,hasnoperistalsis,andcontinuestotheanusastotallyaperistaltic
Theunaffectedsitelooksdilated,plentyofperistalsis,thispartisthemegacolon
Presentationisaneonatewithoutmuconiumpassage,megacolon,andmayvomitfeces
CeliacSprue AnIgAImmuneDiseasetowheatgluten,morespecifically,togliadininwheatproducts(AntiGliadin)
Causesmucosalatrophy,malabsorption,failuretothrive,foulsmellingsteatorrhea
AssociatedwithDermatitisHerpatiformis,avoidglutenproductsandpatientwillliveanormallife
TropicalSprue SimilarmucosalatrophyandmalabsorptionasinCeliacSprue,butwithanunknownetiology
Suspectedtobeaninfection(E.Coli?)thatrespondstoantibioticsandvitamins
Whipples RarediseaseofmaleruralworkersoftheCaribbeancausedbyinfectionbyTropherymaWhippeli
Disease Presentswithdiarrhea,andmalabsorptionwithabundantdistendedmacrophages(survivesinside
macrophages)inmucosaofsmallintestinewithcompletevilli,thatrespondstolongtermantibiotics
Chrons Bimodalage(1030and5070),affectingwhitefemalesusuallytargetingterminalileum
Disease MayoccuranywherealongtheGItract,butoccurswithskippedlesionsandfistulaformation
ThereareNoncaseatinggranulomaswithtransmuralinflammationandhardlyanyriskofcancer
Ulcerative Occurringinthe20sand30sofwhitefemalesthattargetsthecolon,whichiscontinuousfromrectum
Colitis Therearenoskippedregions,nogranulomas,theinflammationislimitedtomucosa/submucosa
Thereisanelevatedriskofcoloncarcinoma.BothCrohnsandUCpresetwithbloodymucoiddiarrhea
IschemicBowel Reducedbloodflowtothebowelforanyreasoncausesischemiatermedmesentericangina
Disease Regionsatriskarethesplenicflexureandotherwatershedareas
Affectstheelderlyorseveretraumavictimspresentingwithhemorrhagicnecrosisand50%survival
Meckels CongenitalDefectofthesmallbowelcommonlyencounteredinchildren,aremnantofvitellineduct
Diverticulum Usuallyasymptomatic,Meckelsmaycontaingastricorpancreaticmucosa,whichmaybleed(brightred)
Foundin2%ofthepopulation,and2%ofthosewillbecomecancerous
Colonic Acquireddefectofthelargebowelcommonlyencounteredinelderlyadultswithlowfiberdiets
Diverticulosis Pouchesformfromincreasedluminalpressure(constipation);pouchesareasymptomatic
Fecesgetsstuckinthem,leadingtoinfection(diverticulitis)whichmayperforate(peritonitis)
Maymimiccancerwithalternatingdiarrheaandconstipationorbloodydiarrhea

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 PathGILiverBiliaryExocrinePancreas

TYPESOFDIARRHEA
Secretory Invasive Osmotic
NegativeforFecalLeukocytes PositiveforFecalLeukocytes NegativeforFecalLeukocytes
cAMPstimulatingtoxins Bloody,MucinousStool LactaseDeficiency
E.Coli(ETEC),Cholera Shigella,Salmonella,EHECE.Coli Laxatives
HighVolumeDiarrhea LowVolumeDiarrhea HighVolumeDiarrhea

BUGSCAUSINGGIINFECTIONS
Bug Character
VIRUS
Rotavirus Mostcommonchildhoodofdiarrhea,transmittedviatheFecaloralroute
NorwalkVirus WalkingDiarrheathatruinscruiseshipvacations
Cytomegalovirus HIVimmunocompromisedonly,GiantCellwithinclusions
BACTERIA
StaphAureus RapidOnset(16hrs)=DiarrheaandVomitingbypreformedtoxin,GramPositive,PotatoSalad
BacillusCereus Reheatedrice(buffetline),PreformedToxin,GramPositive
Salmonella Invasivedisease,3%becomechroniccarriersinbiliarytract,spreadbypoultry,flagellated
ClostridiumDifficile CausesPsuedomembranousColitisafterwidespectrumantibiotic,treatwithVancomycin
EHECE.Coli ShigaLikeToxin,sameasShigella,butcanalsocauseHemolyticUremicSyndrome,0157:H7
Shigella ShigaToxin=Cleavage of60ssubunit=bloodydysentery,nonsystemicinfection
CampylobacterJejuni BloodyDiarrhea,especially in HIV/AIDS associated with Guillain Barre
ETECE.Coli TravelersDiarrhea(Mexico),sameascholeraToxin,waterydiarrhea
YersiniaEnterocolitica GranulomatousMicroabscesses,thisisnotYersiniaPestis(theplague)
VibroCholerae CholeraToxin=ADPRibosylationGs =Turnsonapumpthatextrudeschlorideintothelumen
Massiveamountsofwaterydiarrhea,treatment=parenteralfluid/electrolytes
PROTOZOA
Enteromeaba FlaskShapedUlcerations,canascendandcauseLiver/Gallbladderproblems
Histolytica Hasmultiplenuclei,diagnosedbyseeingprotozoawithRBCsinsideit
GiardiaLamblia Immunocompromisedpatientsordrinking waterfromastream,flagellatedprotozoa
Cryptosporidium MostcommoncauseofdiarrheainAIDs
HELMNITHS
AscarisLumbricoides Bowelobstructioninadultphase
Diphyllobothorium CausesB12Deficiencyafteringestionofrawfreshwaterfish
Latum
Strongyloides AbdominalPainandDiarrhea,LarvaeinSoilpenetrateskin, coughedupinlungs
Enterobius Eatfoodcontaminatedwitheggs=pinworm
Vermicularis causesanalpruritisandeggscomeoutatnight(scotchtapetest)
Microisitsowncoursesoabriefsurveyoforganismsshoulddoyouwell.Questionscanbepicky,butyoushouldbeabletonarrowitdownto
23choicesprettyeasily.Thereisanexcellent(andmorethorough)tableinGoljan,page346edition2.

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