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PathGILiverBiliaryExocrinePancreas

CONGENITALDISEASESOFTHEESOPHAGUS
TracheoesophagealFistula

Atresia

Fistula

Mostcommon
presentationof
atresia/fistula

Esophagushasbothatresia(blindpouch)andfistula(connectiontosomethingelse)
Patientshavethetracheaandesophagusconnected
o Patientsswallowfoodintotheirlungs=aspirationpneumonia
o CoughingandCyanosisduringfeeding
o Amnioticfluidcannotbeswallowed,causespolyhydramnios
Mustbesurgicallycorrected,whichiseasilydone.
o Mostcommon=atresiaofupperesophagusandfistulaofloweresophagustotrachea

EsophagealWebs

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

Achalasia
Esophagus

o
o
o
o
o

BirdsBeak
Stomach
Pylorus

InabilitytorelaxtheLowerEsophagealSphincter(LES)
Presentswithdysphagiaormegaesophagus(cantgetfoodintostomach)
Diagnosedwithbariumswallowrevealingbirdsbeakesophagus
CausedbydeathofganglioncellsintheLES
Treatedwithstentingorsurgicalresection

HEMATEMESISANDBLEEDS
MalloryWeissTear
o
o
o
o

StomachLesionEsophagus

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

EsophagealVarices
o
o
o
o

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

Endoscopywithprotrudingdistendedveins(arrows)

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Sheets

PathGILiverBiliaryExocrinePancreas

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
o Actionofgastricjuicesiscriticaltothedevelopmentofmucosalinjury
papillaeandbasalzone
Morphology
hyperplasia
o Dependentonseverityandexposuretime(twoweeksversussevenyears)
o SimpleHyperemia(redness)maybetheonlyindicator

o InflammatoryInfiltrate=PMNs,Lymphocytes,and/orEosinophils
Redstreaksarehyperemia.
Endoscopicimage.
o BasalZoneHyperplasia>20%ofepithelialthickness
o ElongationofLaminaPropriaPapillae
Clinical

o Commonwithincreasedage(>40)thoughpossibleinchildrenthroughadulthood
MinorEosinophiliainthe
o Severityofsymptomsseverityofdisease(lotsofburningwithoutlotsofchanges)
Esophagusisalmost
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

SalmonVelvetappearance
o GERDlasts20yearsbeforeBarrettssetsin
o Patientgoesfromsevereheartburntonopainspontaneously(progressiveoracute)onendoscopy
o Thisisprecancerouswith3040TIMESriskforadenocarcinoma
o TreatmentwithPPIscanpotentiallyreversebothdysplasiaandmetaplasia

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ColumnarEpithelium
withgobletcells=
Barretts

PathGILiverBiliaryExocrinePancreas

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
HerpesEsophagitis.Inthe

Candidaesophagitis.Thisisafungus

showingpseudohyphae,stained
blackagainstagreenbackground.
Candidanormallylivesinthemouth;
youmusthaveinvasiontocallit
candidiasis.Usuallyoccursinthe
immunocompromised.ItisanAIDS
definingdisease.

TUMORS(BigRobbins806,BabyRobbins413)

immunocompromisedindividual,
lookforCowdryTypeAandCowdry
TypeB.Thereistypicallynuclear
moldingandinclusionsshowing
perinuclearhalos.

MalignantTumorsSqaumousCellCarcinoma

Definition
o Dysplasticcarcinomaofthesqaumouscellsoftheesophagus
EtiologyandPathogenesis
o Obviousimpactofvariousenvironmentalfactorscombinedwithgeneticpredisposition
o Chronicesophagitis,Alcohol,orTobaccocontributetorisk
o Mostcommonesophagealtumorworldwide
GERDBarrettsAdenocarcinomaequaltoormorecommoninUS

SCCshowingKeratinPearls
Morphology
(arrow)amidstdysplastic
o SimilardevelopmenttootherSCC,withcharacteristicbenigntransformationthrough
mucosalepithelium
carcinomainsitu,andpresenceofkeratinpearls
LungEsophagusTumor
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
Tumorgrowingontopof
lungs,fromthemid
stenosis)arealsopossible.
esophagus,meansitmust
beSCC

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PathGILiverBiliaryExocrinePancreas

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

10yearsofheartburnwithouttreatmentforGERD
Grossimageofesophageal
adenocarcinoma.Normal
25yearsofBarrettswithouttreatmentforGERD
mucosa(blue),gastgric

15yearsofadenocarcinomaleadingtotheirdeath
mucosa(red),
adenocarcinoma(yellow)
o ProtonPumpInhibitorTherapypriortoadenocarcinomaformationiscurativeand
reversedmetaplasia/dysplasiabacktoesophagealmucosa
Metaplasiahasgivenwaytodysplasia.Youvegotcancer.
InitialsymptomsofGERDwhere

Theburnbeginstospontaneously
heartburniscontrolledbyPRNantiacids,
followedbyOTCdrugs.Theburnmeans

youresophagusisnormal

Heartburn,AcidReflux,GERD

Cancerousgrowthshowsnosignsorsymptomsuntilyoucant
disappearoverthecourseofyears.You
eat(dysphagia)orafistulaismadetoyourlungs(aspiration
feelbetterbutyouresophageal
pneumonia).Youdiewithin5years(20%5yearsurvival)
510 epitheliumhasundergonemetaplasia
25 years
15years
years

ProtonPumpInhibitorsare

preventativeofdisease.Getan

endoscopytotrackchanges

BarrettsEsophagus

ProtonPumpInhibitorsarecurative.
Theyreversethemetaplasiaand
holdoffdysplasia.Getendoscopyfor
diagnosisandtotrackchanges

ProgressionofGERDtoCarcinoma

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Adenocarcinoma

Youarescrewed.Atthispointitstoo
late,asthesearenastyinvadersand
haveaverypoorprognosis,even
withresection

Death

PathGILiverBiliaryExocrinePancreas

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
forthisdiseaseasanoptionchoice
enlargedrugae,butdonot
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
Gastriniselevatedinthebloodatalltimes,anddoesnotsufferacidcontent
Crosssectionshowingenlarged
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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PathGILiverBiliaryExocrinePancreas

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

Grossviewofpunctuateerosionsinan
otherwiseunremarkablemucosa

normalmucosa(arrowheads)hemorrhagicmucosal
disruption(arrow)

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Multipletinystressulcers,highlightedby
thedarkpigment(digestedblood)onan
otherwisenormalmucosa

PathGILiverBiliaryExocrinePancreas

ChronicGastritis=GastritiscausedbyH.Pylori

Definition
o ChronicMucosalInflammationthatmayleadtomucosalatrophy,intestinalmetaplasia,
dysplasia,andevencarcinomausuallywithouterosion
Pathogenesis
o TypeA:Autoimmunegastritis,FundicType
AntibodiestargetandkilltheParietalCellsandelimateIntrinsicFactor
TypeAisAutoimmune
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
AtrophycausesofGastrinProducingcells(inhibitorystimulus=secretion
H.Pyloriorganismsseen
ingastricgland
ofGastrin)whichleadstooverstimulationofECFcells
Metaplasiaalreadyactivatederroneousgeneproduction
Regenerativechangesrevupreproduction=riskoftransformation
Clinical
o Sxarepersistentacutegastritiswiththesamerange
o SerumGastrinisusuallynormalorslightlyelevated,lumenishypochloridic
o Autoimmuneshowscirculatingantibodies
o H.Pyloricanbeseenonbiopsy

LymphoidAggregatewithhypercellularmucosaof

chronicgastritis

GlandssurroundedbyheavyNeutrophilicinfiltrate
(allthelittlepurpledots)

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Gobletcellsincolumnarepithelium,loss
ofgastricglands.Intestinalmetaplasia.

PathGILiverBiliaryExocrinePancreas

PEPTICULCERDISEASE(BigRobbins816,BabyRobbins417)
PepticUlcers

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

o CausedbyimbalancebetweenGIdefensesandacid/pepsin
Gastriculcer.Singular,
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
o Withtx(H+PumpBlockers/OmeprazoleandH.PyloriAntibiotics)ulcershealinweeks
lesion(lesionincenter)
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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PathGILiverBiliaryExocrinePancreas

GastricAdenocarcinoma

Definition
o Mostcommonmalignantneoplasmofthestomach
Pathogenesis
o Largelyunknown,thoughlinkedtoallriskfactorsofchronicgastritis,inparticular:
Smoking,EtOH,H.Pylori,AutoimmuneGastritis
SmokedFish(Japan)withhighamountsofNitrosaminescandoitto
o Thereisanaturalprogressionfromacutegastritischronicgastritisintestinal
metaplasiadysplasiacarcinomathatisacceleratedparticularlybysmokingand

H.Pyloriinfections
SignetCellspathognomonic
Morphology
forGastricCarcinoma
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
productofintestinalmetaplasiafromHPyloriinfections,welldifferentiated
plastic.
Diffuse=Poorlydifferentiated,stronglyinfiltrative,signetringonhistologyand
linitisplasticaongross,notlinkedtoH.Pyloriinfections
Clinical
o Typicallyaninsidiousonsettumor,earlysatietyandvomitingarelatesigns
Nitrosamines,H.Pylori,
o Outcomedependentondepthofinvasion:Early=95%,Advanced=15%5yearsurvival
SignetRingCell,Virchows
o
MetastaticSite
Node,LinitisPlastica
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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PathGILiverBiliaryExocrinePancreas

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
o Patientspresentwithmassivediarrhea,flatulence,weightloss,andfatigue
DermatitisHerpatiformis
isadepositionofIgA
o Patientsareinfancyupuntilmidadulthood
gliadincomplexesatthe
o Linktotheskinblisteringdisease,DermatitisHerpatiformis
dermalepidermal
o Withdrawalofglutenfromthedietiscurativewithoutsequella
junction.
TropicalSprue
LookslikeCeliacSprue,
butisfrominfection,not
autoimmune

o
o
o
o

Malabsorptivediarrheacausedbyinfectionofunknownorganism,suspectedEColi
RespondswelltoB12,Folate,andantibiotics
Usuallyinvolvesthedistalsmallintestine
Thereisatrophicvilli,resemblingceliacdisease,butisnotanautoimmunedisease

WhippleDisease

EMofbacilliin(arrow)and
outside(arrowhead)
macrophage

VilliwithPASpositive
macrophagesinthelamina
propria

Definition
o RaresystemicdisordercausedbyinfectionbyTropherymaWhippeliaffectingintestine,
jointsandCNS
Pathogenesis
o Unknown,organismisanactinomycetethatlivesinmacrophages
o RiskincreasesintheCaribbean,CaribbeanRuralFarmersDisease
Morphology
o Smallintestinalmucosaladenwithdistendmacrophagesinthelaminapropria
PASpositiveforundigested/incompletelysosomes
OrganismscanbeseenonEM
o Thesemacrophagesarefoundinjoints,brain,andheart
o Inflammationislowtoabsentthereisnoinflammatoryreaction,villiareintact
Clinical
o Respondswelltolongtermantibiotics
o Typicallymales(10:1)overfemales,andusuallyrural
o Diarrhea,Malabsorption,andArthralgiatipyouoff,obstructionofGIorBiliaryTract

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PathGILiverBiliaryExocrinePancreas

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
o Intermittentattacksofdiarrhea,fever,abdominalpain,anorexia,andweightloss
Bariumenemashowsa
stricture(arrow).Stricture
o Occursinwhitesmorethanblacks,jewsmorethanotherwhites
isacomplicationofCrohns
o WithterminalilealinvolvementB12deficiency,perniciousanemia,andmalabsorption
butnotUC.stringsign
ofbilesaltsleadtocorrespondingsymptoms
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PathGILiverBiliaryExocrinePancreas

UlcerativeColitis

ContinuousUlceration.
Everythingred,fromthe
rectumtothearrow,is
affected.Totheright
(upstreamtowardssmall
intestine)oftheorange
arrow is normal.

Definition
o Inflammatoryboweldiseaselocalizedtothecolon,formingulcerativelesionsina
continuousfashionandwithoutgranulomas
Morphology
o Therearenoskiplesions,andinvolvestherectumextendinginaretrogradefashion
o Psuedopolypsmaybeabundant,granulomasareabsent,cryptabscessespresent
o Thinfloppywallbecausetheinflammationislimitedtothemucosa
ClinicalFindings
o Intermittentattacksofbloodymucoiddiarrheaandabdominalpain
o Thereis,forsomereason,alinktoprimarySclerosingcholangitis(seeliver,below)
o Increasedriskofcarcinomawithchronicinflammation

TUMORS(BigRobbins856,BabyRobbins436)
TumorsoftheSmallIntestine

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

BenignColonNeoplasms=AdenomatousPolyps=ColonicAdenomas
Benign,precancerouslesionsoftheluminalwall
Morphologies
o PedunculatedVsSessile
Pedunculatedpolypshaveastalk
riskforcancer

Sessilepolypsareflatandhavenostalk
PedunculatedPolyp
riskforcancer
ColonStalkPolyp
o TubularVsVillous
Tubularlookslikenormalcolon,withtubulesthroughoutthepolyp
riskforcancer
Villoushavefingerlikeprojectionsalloverthepolyp

TubularPolypHistoSection
riskforcancer
Tubulovilloushavecombinationsofboth
Presentation
o Maypresentwithoccultbloodinstool
o Warrantacolonoscopy,samplingofpolyps(removal)andhistologicsectioning
o Thepresentationismorebasedonwhatcausedthem:asinglepolypcommonwith
agingor1000polypsfromFAP.
SessilePolypStalk

12|O w l C l u b R e v i e w S h e e t s

PathGILiverBiliaryExocrinePancreas

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

Lookelsewherefortumors,suchasthelungsorskin
dysplasiaorcarcinoma.

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)

13|O w l C l u b R e v i e w S h e e t s

PathGILiverBiliaryExocrinePancreas

CONGENITALANDANTAMOICDISEASESOFTHECOLON(NoRobbinsPage,throwingthemtogether)
Volvulus
o
o
o

Twistingofthebowelaboutitself
Cancauseobstructionofthebowel
Twistingofbloodvesselscanleadtoischemiaandinfarctionwhichthenresultin
perforation,peritonitisanddeath

BowelLoopedAroundBowel

Intussusception
o
o
o

Bowelshovedinsidebowel

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

MeckelsDiverticulum
o
o
o

BlindoutpouchingSmallIntestines

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

HerschbrungsDisease=CongenitalMegacolon
o
o

Bariumenemaofcongenital
megacolon.Unaffectedsegment o
backtowardsthemouthis
o
dilated,affectedsegmentis
normal.Thestartoftheaffected
o
segmentismarkedbythe
arrow.

Congenital
Causedbythefailureofneuralcrestcellstomigratetothedistalcolon
Histologicdiagnosisisdependentonabsenceofgangliawithinbothmeisners
andauberbachsplexus
AffectedSegmentisnormal,UnaffectedSegmentismassivelydilated
UnaffectedsegmentpushesstoolthroughGItract,andgetsbackedupatthe
affectedsegment,whichdilatestoaccumulatethebackedupstool
Therewillbeaperistalsis(becauseoftheabsenceoftheentericnervoussystem
ganglia)fromwheretheaffectedregionstarts,totheendofthecolon
Babypresentswithoutpassageofmuconiumandwithamegacolon
MegacolonitselfmaybetoxicorfromChagasdisease,butbaby+megacolon=
Herschbrungsdisease
Surgicalresectionoftheaffectedsegmentisrequired.

14|O w l C l u b R e v i e w S h e e t s

PathGILiverBiliaryExocrinePancreas

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

15|O w l C l u b R e v i e w S h e e t s

PathGILiverBiliaryExocrinePancreas

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)
o

Cirrhosis

DefinitionandCharacteristics
o Anendstagechronicliverdiseasemarkedby:
BridgingFibrousSeptae=lotsoffibrosislinkedtogetherbetweenportalveins
ParenchymalNodules=islandsofproliferatinghepatocytestrappedinfibrosis
GlobalDisruptionofhepaticarchitecturewithvascularreorganization
Etiology
Oncepresent,theoriginalcausemaybe
AlcoholLiverDisease
6070%
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

16|O w l C l u b R e v i e w S h e e t s

PathGILiverBiliaryExocrinePancreas

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

17|O w l C l u b R e v i e w S h e e t s

PathGILiverBiliaryExocrinePancreas

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

18|O w l C l u b R e v i e w S h e e t s

PathGILiverBiliaryExocrinePancreas

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
LiverFailure

Cirrhosis

Portal
Hypertension
Jaundice
and
Cholestasis

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

19|O w l C l u b R e v i e w S h e e t s

PathGILiverBiliaryExocrinePancreas

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
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)
Schematicforthepiecesof
o ProteinX(HBx)necessaryforviralreplication&implicatedinhepatocellularcarcinoma
virus
InfectionandPathogenesis
o HepBdoesnotcausehepatocyteinjury;itistheimmuneresponse(CD8CytotoxicT
Cells)toinfectedhepatocytesthatcauseshepatocyteinjury
Thestrongertheimmuneresponsetheworsetheacutehepatitisbutthelower
theriskforchroniccarrierstate
RiskofcarrierstateforNeonates,Immunocompromised
o HepBishearty,andistransmittedthroughsemen,saliva,urine,sweat,blood,lactation
Mostpeoplerecoverquickly,
riskforIVDrugUsers,AccidentalNeedlestick,homosexualmales
somestayashealthycarriersa
smallfractiongoontochronic
VerticalTransmissionfrommomtobabyduringbirthispossible
persistentinfection),anda
o HepBhasaprolongedincubation(624weeks),riskofunknownviralspread
minisculefractiongoesto
o Infectionhas4possibilities
fulminatedisease
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
20|O w l C l u b R e v i e w S h e e t s

PathGILiverBiliaryExocrinePancreas

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!

21|O w l C l u b R e v i e w S h e e t s

PathGILiverBiliaryExocrinePancreas

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
o
o
o
o

Hepatocytesshowdiffuseswellingcalledballooningdegeneration
Cholestasisisaninconsistentfinding,oftencausedbybileorpigmentplugs
Necrosiscanbeseenwithcytolysisprecedingmacrophageaggregates
Apoptosis,mediatedbyTcells,causeshrunken,highlyeosinophilicnuclei
InflammatoryCellscanbeseenwithinthelumenandmayspillintoparenchymacausing
BallooningDegenerationand
necrosis,termedinterfacehepatitis
lossoflobulararchitecturein
Chronic
acuteviralhepatitis

o Steatosis=fattychangewithinthehepatocytes
o GroundGlassCells=evenlarger,moreballoonedthanballooningdegeneration
o InterfaceHepatitis+Bridgingnecrosisareharbingersofliverfailure
o Fibrousdepositionreplacesthenecrosisandisthemarkerofirreversibledamage

PeriportalFibrosisstatsitoff,thenregionsoffibrosisbegintoconnect,called
portaltractexpansion,
bridgingfibrosis,untiltherearesmallislandsofregeneratinghepatocytes
interfacehepatitis,lymphoid
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)

22|O w l C l u b R e v i e w S h e e t s

Diagrammaticrepresentationofthechangesin
chronichepatitis.Usethistogetwhatis
meantbythedifferentterminologyinboth
chronicandacute.Foramoreclearpictureof
both,seeimages1817inBigRobbins

PathGILiverBiliaryExocrinePancreas

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

spaces)arepresentwithinhepatocytes. alymphocyticinfiltrate
Thecellsarefilledwithfat.Indicativeof
surroundingthebileduct,which

fattychange(EtOH,HepC)
hasanabnormalshape

(amorphousfromcircular).
IndicativeofHepC

InterfaceHepatitis.Thelymphocytes
fromaportaltriad(youcanseethe
bileduct)buttupagainstthelimiting
plateofhepatocytes.Thereis
necrosisofthehepatocytesonthe
rim,butnolymphocyteswithin
parenchyma

Grade1PeriportalFibrosis.Inflammatory

Grade2SeptalFibrosis.Thefibrosis
cellscomeoutoftheportaltracts,but
spillsintotheparenchyma,but
doesnotspillintotheparenchyma;there irregularly,andneartheportaltracts

isonlyinterfacehepatitiswithinterface
necrosis.

23|O w l C l u b R e v i e w S h e e t s

Grade3BridgingFibrosis.Fibrosis
fromdifferentportaltractsbeginto
connectwithsmalltractsoffibrosis.

Grade4Nodulesrepresentgrade4.Purple
islandsofregeneratinghepatocytes
surroundedbyfibrosisindicatedGrade4
hepatitis,cirrhosis.

PathGILiverBiliaryExocrinePancreas

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

Tetracycline, salicylates, yellow phosphorus, ethanol

Macrovesicular fatty change

Ethanol, methotrexate, amiodarone

Centrilobular necrosis

Bromobenzene, CCl4, acetaminophen, halothane, rifampin

Hepatitis, acute and chronic

Methyldopa, isoniazid, nitrofurantoin, phenytoin, oxyphenisatin

Fibrosis-cirrhosis

Ethanol, methotrexate, amiodarone, most drugs that cause chronic hepatitis

Granuloma formation

Sulfonamides, methyldopa, quinidine, phenylbutazone, hydralazine, allopurinol

Cholestasis (with or without


hepatocellular injury)

Chlorpromazine, anabolic steroids, erythromycin estolate, oral contraceptives, organic


arsenicals

AlcoholicLiverDisease

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

Zoomedinviewofsteatosis,
Microscopic=macrovesicularnodules(chronic)ormicrovascular(acute)
largevacuoleswithin
Abstinence=Recovery
parenchyma
24|O w l C l u b R e v i e w S h e e t s

PathGILiverBiliaryExocrinePancreas

BallooningDegeneration,MalloryBodiesandaNeutrophilicreaction,when

AlcoholicHepatitis
together inadrinker,arepathognomonicforEtOHHepatitis
Characterizedby4changes:
HepatocyteSwellingandNecrosis=directhepatocytetoxicityresultsin
ballooningdegeneration
MalloryBodies=eosinophilicinclusionsofdyinghepatocytesare
characteristicof,butnotuniquetoalcohol
NeutrophilicRxn=Alcohol+itsmetabolite,Acetaldehyde,inducechanges

Zoomedimageof
inhepatocellularproteinsleadingtoanimmunologicrxn.Lymphocytes
eosinophilicinclusions,
entertheportaltractsandspillintoparenchyma
MalloryBodies
Fibrosis=activationofstellatecells,particularlysinusoidalperivenular
fibrosis;periportalmaypredominate.Fibrosisprogressestocirrhosis.
Liverismottledred,stainedwithbile,&possessnodulesandfibrosis(portends
comingcirrhosis)
Abstinence=Recovery
o AlcoholicCirrhosis
Finalandirreversiblechangeofcontinuedfibrosis

Presentswithamicronodularliver(opposedtoHepVirus)
Fattyliver(white)withsome
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

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

25|O w l C l u b R e v i e w S h e e t s

PathGILiverBiliaryExocrinePancreas

METABOLICLIVERDISEASE(BigRobbins907,BabyRobbins460)
NonalcoholicFattyLiver(NAFL)andNonAlcoholicSteatoHepatitis(NASH)

BallooningDegeneration,MalloryBodiesanda
Neutrophilicreaction,whentogetherbutnotina
drinker,arepathognomonicforNASH

Morphologyofalcoholicfattyliverwithoutthehistoryofdrinking
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)
26|O w l C l u b R e v i e w S h e e t s

PathGILiverBiliaryExocrinePancreas

WilsonsDisease

Definition
o Autosomalrecessivedisorderwithaccumulationofcopperintheliver,brain,andeye
Ballooning+MalloryBodies
Pathogenesis
o AutosomalRecessivemutationofacopperATPasecalledATP7Bonchromosome13
Excesscoppercannotbeexcretedfromhepatocytesintobileforelimination
o Multiplemutationshavebeenfound,patientsareusuallycompoundheterozygotes
(missingpieceAononechromosomeandmissingpieceBontheother)
o Copperhandlingcapacityofceruplasminisexceededat~5yearsofagewhereacute
illnessresultsfromcopperspillingintothebloodstreamanddepositinginorgans
Ballooningdegeneration,
Morphology
MalloryBodies,Portal
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)
o Psychosisorparkinsonismispossible(basalganglia)
Rhodaninestainscopperas
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
o Avoidsmoking(emphysema),getalivertransplant(cirrhosis,HCC,andPi)
Immunohistochemistry
for1AT
27|O w l C l u b R e v i e w S h e e t s

PathGILiverBiliaryExocrinePancreas

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
onionskinningfibrosisofPCS

PrimaryBiliaryCirrhosis.Lymphocytesand
plasmacellsfillabiletractwhileagranuloma
formstothebileduct(arrow)

28|O w l C l u b R e v i e w S h e e t s

SecondaryBiliaryCirrhosis.Yellowgreenliverfrom
bilestainingaftersecondarybiliaryobstruction.Bile
lakesarelikelypresentaswellasafuturefibrosis

PathGILiverBiliaryExocrinePancreas

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)

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

CavernousHemangioma,akaHemangioma
o MostCommonbenignlesionoftheliver
o Consistsofwellcircumscribedlesionsofendotheliallinedvascularchannels
o Appearasdeepred,softnodulesbeneaththecapsularsurface
o Thesearenotmetastatictumorsanddonotrequirebiopsy
CavernousHemangioma.
LivercellAdenoma
GrossimageofSoft,red,
Adenoma.Normallooking
strawberryappearance
hepatocyteswithoutbile
o Benignneoplasmsarisingfromhepatocytes
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
o Anelevatedfetoprotein(AFP)inachildisagoodtipoff
centralscar,butisalarge
nodule(1/2theliver)andis
Angiosarcoma
thesamecolorasliver
o Resembleangiosarcomasoccurringanywhere
o Areassociatedwithcarcinogenicexposure(vinylchloride,arsenic)whenintheliver
o Extremelypoorprognosiswithdeathoccurringin<1year
29|O w l C l u b R e v i e w S h e e t s

PathGILiverBiliaryExocrinePancreas

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
o Surgeryistheonlytreatmentoption:resectionandtransplantoftenresultin
centrallumen,onefilledwith
bile(arrow)
reinfection(withHepB)orinrecurrenceoftumor
FibrolamellarHCC
o Occurinyoungpeoplewithnormalliversandcarryagoodprognosis
o Mentionedinlecture,doesntshowupinreviewbooks/Kaplan

30|O w l C l u b R e v i e w S h e e t s

PathGILiverBiliaryExocrinePancreas

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

(3) CholesterolNucleationisaccelerated(calciumsalts,changein[protein])
Allthegreenish,yellowthings,of
(4) MucousHypersecretiontrapsthecrystals,allowingthemtoformstones
varioussize.Theyareyellowonthe
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)
31|O w l C l u b R e v i e w S h e e t s

PathGILiverBiliaryExocrinePancreas

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.
o UpperRightQuadrantPain,LowGradeFever,Nausea+Vomiting,Tachycardia
Shinycoat(serosal)is
o AbdominalTendernesswithpositiveMurphysSign,freeofjaundice(usually)
interruptedbybrief
periodsoffibrin.
Deeppalpationofgallbladderwillterminateinspiration(becauseofpain)
Hemorrhagepresenton
o
Maybeanimmediatemedicalemergencyormayresolvewithoutintervention
thetopright
o Most(90%)calculouscholecystitiswillrecur
o Potentialcomplicationsincludeperforation/peritonitis,superinfection/cholangitisand
fistulaformationtotheduodenum
ChronicCholecystitis

Thickenedwalls(white)
withgallstonesinside.

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

32|O w l C l u b R e v i e w S h e e t s

PathGILiverBiliaryExocrinePancreas

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

33|O w l C l u b R e v i e w S h e e t s

PathGILiverBiliaryExocrinePancreas

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
ErythroblastosisFetalis
(Hemolysis)

Character
RhmomhasasecondRh+ baby,momsantibodiesdestroybabysRBCs
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

Disease
HepA

HepB

HepC

HepD

Bacterial,
Fungal,
Parasite
Schistomsa
Clinorchis
Senensis

INFECTIOUSHEPATITIS
Character
FecalOralRoutefortransmission
CausesOnlyAcuteHepatitis
RNAvirus,vaccineavailable
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
IVDrugsandSexualContact fortransmission (adults)orposttransfusion(anemic)
CausesMostlyChronicbutmaycauseAcuteHepatitis;
RNAvirustransmittedthroughblood
Usuallyprogressestocirrhosis,smallriskforHCC
IVDrugsandSexualContact for transmission
Cannotinfecthepatocytesonitsown,requiresHebBcoinfection
WorseningHepBinfection(hepatitisandHCC)orproducesfulminanthepatitis(superinfection)
Formabscesses,usuallyacquiredoutsideofUS
Commonpyogenicinfections=sameforcholangitis=GIflora(E.Coli,Klebsiella,etc)
Amebiasis(entamoebahistolytica)andSchistosomiasiscommonparasites
CausesPortalHypertension,otherspeciesmaycausebladdercancer
RiskofCholangiosarcoma,causesbiliaryobstruction

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PathGILiverBiliaryExocrinePancreas

Disease
CholesterolCholelithiasis
Fat,Forty,Fertile,Female
PigmentCholelithiasis

Cholestasis

Cholangitis
BiliaryAtresia
Primarybiliarycirrhosis

DISEASESOFTHEGALLBLADDER
Character
CholesterolStonesareyelloworgreen,formedfromcholesterolcalciumsalts
RiskwithObesity,Pregnancy,OralContraception,Female,NativeAmerican
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
FocalNodular
Hyperplasia
Cavernous
Hemangioma
LivercellAdenoma

Metastasis

Hepatoblastoma

Angiosarcomaof
Liver
Hepatocellular
Carcinoma(HCC)

FibrolamellarHCC
Carcinomaofthe
Gallbladder
Carcinomaofthe
BileDuctsand
Cholangiosarcoma

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

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PathGILiverBiliaryExocrinePancreas

EnzymeorMarker

AspartateAminoTransferase(AST)
AlanineAminoTransferase(ALT)
LactateDehydrogenase(LDH)
SerumBilirubin
Total(everything)
Direct(conjugated)
SerumBileAcid

LABORATORYMARKERSOFLIVERFUNCTION
WithInjuryor Rationale
Dysfunction
HepatocyteInjury

Allthreearemarkersforinjury,enzymescontainedwithin
hepatocytes.WithHepatocellularnecrosisorapoptosis,enzymesare

released,soserumlevelsincrease,amarkerforinjury.

BiliaryFunction

Ifunconjugated,riskforkernicterus;lipidsolubleunconjugated
canpenetrateBB,cannotbeexcretedrenallyandisneurotoxic

Ifconjugated,mostlikelysecretionmutationorbiliaryobstruction.
ConjugatedBilirubinnontoxicandexcretedinurine

Bileacidsaremadeintheliver,secreted,andrecirculatedthrough
enterohepaticcirculation.Increasedlevelsmeansbiliaryobstruction.
Causespruritis,bilelakesinliverwillbeseen

SerumAlkalinePhosphatase

Albumin

ProthrombinTime
(PTandaPTT)
Ammonia

Containedinbiliarycells,releasedduringcholestasis,asbileacids
destroyliningofbiliarywalls,markerofbiliarydamage
HepatocyteFunction
Thelivermakesalbumin.Iftheliverisntworking,itwontmake
albumin.Thisincreasesriskforascitesandedema
Livermakesclottingfactors.Iftheliverisntworking,itwontmake
theclottingfactors,soyouwontclot,andclottingtimeincreases
Theliverprocessaminoacids(ureacycle).Iftheliverisntworking,it
buildsupammonia,whichcancausehepaticencephalopathy

PANCREASTUTORIALSESSION(wasntreading,butknowtheseexist)
Disease
Agenesis

Character
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
Barretts

Location
Esophagus

Adenocarcinoma

Esophagus

SqaumousCell
Carcinoma

Esophagus

GastricCarcinoma Stomach

MALTomas

Stomach

StromalTumors

Stomach

Adenomatous
Polyps

Colon

Familial
Adenomatous
Polyposis(FAP)
Gardner

Colon

Turcot

Colon

HNCPP

Colon

PeutzJeghers

Colon

Colonic
Adenocarcinoma

Colon

Carcinoid

Colon

Colon

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

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PathGILiverBiliaryExocrinePancreas

DISESASESOFTHEESOPHAGUS
Disease
Fistula
Atresia
Webs
Achalasia

Stricture

Mallory
Weiss
Tears
Esophageal
Varices

GERD

Barretts
Esophagus

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

DISEASESOFTHESTOMACH
Disease
Diaphragmatic
Hernia
HiatalHernia

Pyloric
Stenosis
Menetriers
Disease
Zollinger
Ellison
Acute
Gastritis

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

39|O w l C l u b R e v i e w S h e e t s

PathGILiverBiliaryExocrinePancreas

Chronic
Gastritis
Ulcersin
General
GastricUlcers

Duodenal
Ulcers

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

DISEASESOFTHECOLONANDSMALLINTESTINE
Character
Loopingofthebowelarounditselfleadingtobothobstructionandinfarctionofbowel(elderly)
Telescopingofthebowelintoitselfleadingtobothobstructionandinfarctionofbowel(infants)
Aherniaisaloopofbowelpenetratingamuscularwall
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
Disease
Volvulus
Intussusception
Incarcerated
Hernia

40|O w l C l u b R e v i e w S h e e t s

PathGILiverBiliaryExocrinePancreas

Secretory
NegativeforFecalLeukocytes
cAMPstimulatingtoxins
E.Coli(ETEC),Cholera
HighVolumeDiarrhea

TYPESOFDIARRHEA
Invasive
PositiveforFecalLeukocytes
Bloody,MucinousStool
Shigella,Salmonella,EHECE.Coli
LowVolumeDiarrhea

Osmotic
NegativeforFecalLeukocytes
LactaseDeficiency
Laxatives
HighVolumeDiarrhea

BUGSCAUSINGGIINFECTIONS
Bug
VIRUS
Rotavirus
NorwalkVirus
Cytomegalovirus
BACTERIA
StaphAureus
BacillusCereus
Salmonella
ClostridiumDifficile
EHECE.Coli
Shigella
CampylobacterJejuni
ETECE.Coli
YersiniaEnterocolitica
VibroCholerae
PROTOZOA
Enteromeaba
Histolytica
GiardiaLamblia
Cryptosporidium
HELMNITHS
AscarisLumbricoides
Diphyllobothorium
Latum
Strongyloides
Enterobius
Vermicularis

Character
Mostcommonchildhoodofdiarrhea,transmittedviatheFecaloralroute
WalkingDiarrheathatruinscruiseshipvacations
HIVimmunocompromisedonly,GiantCellwithinclusions

RapidOnset(16hrs)=DiarrheaandVomitingbypreformedtoxin,GramPositive,PotatoSalad
Reheatedrice(buffetline),PreformedToxin,GramPositive
Invasivedisease,3%becomechroniccarriersinbiliarytract,spreadbypoultry,flagellated
CausesPsuedomembranousColitisafterwidespectrumantibiotic,treatwithVancomycin
ShigaLikeToxin,sameasShigella,butcanalsocauseHemolyticUremicSyndrome,0157:H7
ShigaToxin=Cleavage of60ssubunit=bloodydysentery,nonsystemicinfection
BloodyDiarrhea,especially in HIV/AIDS associated with Guillain Barre
TravelersDiarrhea(Mexico),sameascholeraToxin,waterydiarrhea
GranulomatousMicroabscesses,thisisnotYersiniaPestis(theplague)
CholeraToxin=ADPRibosylationGs =Turnsonapumpthatextrudeschlorideintothelumen
Massiveamountsofwaterydiarrhea,treatment=parenteralfluid/electrolytes
FlaskShapedUlcerations,canascendandcauseLiver/Gallbladderproblems
Hasmultiplenuclei,diagnosedbyseeingprotozoawithRBCsinsideit
Immunocompromisedpatientsordrinking waterfromastream,flagellatedprotozoa
MostcommoncauseofdiarrheainAIDs
Bowelobstructioninadultphase
CausesB12Deficiencyafteringestionofrawfreshwaterfish
AbdominalPainandDiarrhea,LarvaeinSoilpenetrateskin, coughedupinlungs
Eatfoodcontaminatedwitheggs=pinworm
causesanalpruritisandeggscomeoutatnight(scotchtapetest)

Microisitsowncoursesoabriefsurveyoforganismsshoulddoyouwell.Questionscanbepicky,butyoushouldbeabletonarrowitdownto
23choicesprettyeasily.Thereisanexcellent(andmorethorough)tableinGoljan,page346edition2.

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