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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)
1|O w l C l u b R e v i e w
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
2|O w l C l u b R e v i e w S h e e t s
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
3|O w l C l u b R e v i e w S h e e t s
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
4|O w l C l u b R e v i e w S h e e t s
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)
5|O w l C l u b R e v i e w S h e e t s
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)
6|O w l C l u b R e v i e w S h e e t s
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)
7|O w l C l u b R e v i e w S h e e t s
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
8|O w l C l u b R e v i e w S h e e t s
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)
9|O w l C l u b R e v i e w S h e e t s
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
10|O w l C l u b R e v i e w S h e e t s
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
11|O w l C l u b R e v i e w S h e e t s
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
Centrilobular necrosis
Fibrosis-cirrhosis
Granuloma formation
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
34|O w l C l u b R e v i e w S h e e t s
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
35|O w l C l u b R e v i e w S h e e t s
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)
36|O w l C l u b R e v i e w S h e e t s
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
37|O w l C l u b R e v i e w S h e e t s
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)
38|O w l C l u b R e v i e w S h e e t s
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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