Systems 1 Test 4

'

,1

ULCERATIVE AND INFLAMMATORY LESIONS Aphthos ulcers (Canker ulcers): * Verycommon * More commonin l"t two decades(triggeredby stress,fever, indigestion), * Small,round,shallow,painful,singleor in groups,covered rim on: witlr gray-rvhiteexudate,erythemalous

lP*t'oRAtcA\rnY,l L____TePFTAGUS I

- softpalate,

-buccolabialmucosa,

- lateralbordersof tongue * Autoimmune(?),selflimitedresolvewithin feeweeks

Herpesvirus infection: .$ Verycomnon condition,causedby HSV-I t Transmined by kissing ir, Remainsdommt withingmglia (trigeminal),reactivated by: - fever, sun - cold exposue - respiratoryinfection €. Singleor multiplevesicleson lips+ shallowpainfirlulcers t Diagosis: Tzanktest

-_\-_-/j

e;

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Candida: O Nommalinhabibntof oralcaviry(30-40%) O Causesdiseasewith impairmentof tle usualprotective (diabetes mechanisrns mellitus,glucocorticoid therapy, immunodeficiencv): - Thrush: adherent white plaques anywhere u'ithin oral cavity - May spread to esophazus and !!9q!-+ visceral lesions OMicroscopic: budding firngal hyphae and ovoid yeast cells, necronc mucosa

CANCERS OF ORAL CAVITY AND TONGUE

AcquiredimmunodeficiencJ'syndrome: Advanced cases are often associated with lesions in oral car"itv:

(l) Candidiasis (2) Herpeticvesicles 13)Microbialinfections+glossitis (a) AIDS: Kaposi'ssarcom4 introralpurpricnodularmmses

rnf6r|4nf

ts 3% ofall cancersin USA E 50%deathwithin 5 vears: may havealreadymetastasized beforethe - Earlv metastases, lesionis discovered - OId ase(notbefore40 years) E Site:Lateralmarginsoflower lips Floorof mouth Lateralbordersofmotile tongue EIN.E. : stansaW palpablemass, malignantulcer E Microscopic:squamous cellcarcinom4well differentiated, keratinizing E Clinical:as).mptonatic, localpain,difficultyin chewing

erd'

tlarqedl,+ywhnodes

ocalr-s H.Ar.-l'l1ffitumorapyws SALIVARY GLANDS

Siaradenitis: i yt0t4h4mA.+r-nnOf S4t i ('l Mumps: )

- AII salivary glandsespeciallythe parotiddiffirse interstitial inflmmation, mononuclear cell infiltrate

inchirdhood, - Selfiimited buri,,.aurtr-oYiJ.9#lj*i,itir-

st.''tirv (/Er

afu p! temi niQrnrS Juhrleg

(2) Autoimmme(SjoCren's syndrome): all salivaryglandsand

grmd. racrimar glaydso hearrfS tnfiltald.

(3) Basterial:secondary to ductobsauctionby stone

*,, i

srar Leraloccryu(ltvfis agrntrxf+"' luoslalrnn &l:.:-"

ffi,w" i rcptarcd serretrm.

Nomal aqumous mu@sa at the right (*), squmous cell cilcinoma

(LP) infiltrating submuosamd muscles

Salivaw gland tumors: - 80%in parotid gl arlrds 4p6l - 80%arebenigl Age 66-?$ deiade, equal in both sexes -

a' -',l6yna:

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latuw

tgltu$um

f"

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CfnlqV) "*,-v

oi rund

f

Slowly growing, well demarcated,encapsulatedpainless swelling at mgle ofia+r" fAOn&bW ,

f

Benign, l07o recur after excision, multiple projections oftle tumor penetrate tlre capsule-) adequate resection to prevent recurence. Primary or recurrent benign tuinors present for mmy yers (10-20), rnalignancy may occur

el+hwqLfuntftt\,btrf SonrJrtyu s ul inUaoL[sg|"hssu-L. Quye,nJ

Mlxoid stroma similu to cetilage with interpersd isleds ud strilds ofmvo@ithelial @lls

*#' lnnuawh

bat*q

NutirnpolfaN F,t+J, a{st,

-Trffi.y' ?t-:?w

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Pathogenesis: (l ) Primary acalasia:lossof intriosic inhibitory innewationof lou'eresophageal sphincter(unknou,n origin)

PU

illo rrt(164 icaj cogf-s

trc.

+{ru"nncd. inflammation and ulceration-+ s'quambdscell m;cinoma

dysphagi"-tad - Clinically: progressive @11i.l l@fh noctumalregurgitationandaspiratiouoffood

p"i"reftoatsno.J (esophoqifiG)

q":Pttry',.s

rnotur: p,rbffir t inWbr

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pr

rytc+1 Paraesophagea.lhemia: hemiation of part of gastric fundus beside dre esophagus

): Herniationofdre stomachthroughfte esophageal hiatusin fte diaphragmdueto enlargementofheatus andlaxity of comective tissuearound i Commonlyacquiredcondition i Unknowncause

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Complications: ( I ) Ulceration.stricture (2) Bleeding

Urdtac etdeF

.6,p}Ff]1j; (3)Metaplasia+Banefiesophagus

ffi 4horasc rno.u(s

eauorndttt tflirhd,ffi

bosldL

Clinical: symptomsdueto gstroesophagealreflux: ( I ) Regurgitationof food (2) Heartpain (3) Exacerbatedin recumbentpositionthat facilitates the reflux

Sliding hemia: cap ofgastric cardia moves upward above the diaphragrn

sr&kA

"/

rt+orrrlpftoeuS Add.WFin t"nar PH'I-?' di'wch&6 muccis

o Complicationof longstandinggastroe6FmEffi%!ffix. o Replacement of ofthe squamous epitheliumofesophagus mucus-secrefing columnarcellsepidrelium(metaplasia) tr Most commonin lower one-dtirdof esoohazus o Pathology: ( t ) Lesionshows3 Spes of metaplasia - Qg4fqc-like mucus glmds (no parietal cells or chiefcells) - Epithelium simila to fundus of stomach (glands with

S'*t'd

parietalandchiefcells)aleid, fr4|pirn

fid

n

epithelim with gobletcells - lntestinal-like (2) Inflammatorycells (3) lJlcerationor evenstricturefomation (4) Lesionoccursin patches or linesthe entireesophagus (5) lncreasedrisk (30-40tines) of malisnanttansfoimation into (periodicbiopsyis recommended) adenocarcinoma

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: swel;tol mrrclsh*-ho!lc..t,r Coilrac+p,-Jlonc f(un

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Dysploia with Bffim emphagus: olunnu with

epitheliat ells

Esophagus: lower part with dad( red mucosa (Buffi)*

ulq€r,dllP ln vv&rcotgJ ESOPHAGITIS Commonin Westerncountries andUSA (10-20%of adult popuration) ql} W4 ba COn Causes: (l ) Refluxof gastriccontents (reflexesophagitis, themost mostfiequen|:. efficiencyofesophaeeal antirefluxmechmism - Decreased ofhiatal hernia - Presence - hcremedgastricvolume.conFibutesto the volume ofrefluxedmaterial mucosadueto - Reductionofreprative capacityofesoplrageal prolongedexposure to gasricjuice

* lnges*ion (acids, # ivri+an+s akoli,l,

(2) Ingestionof initants(acids,alkalis,hot fluids,alcohol) (3) lnfectronssuclrasherpesandcandidaalbicansin

parients Csophql ihs immunosuppressed

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- Largely limited to - Dysphagia and

lnil4 - c&.lo€r{cra-Ar{168 dn grrr-c, - trleg-

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v

cpr{a.o.ltum

Herpes simplex: punched ot ulers with brom-red white nomd mu@sa

bre,

anhpt*tek)hcVurni{rn4, t/

r4p1ven1Bl*

rombrned,./ ra4J@frTyl of sphrnCler

bul,,^,t'o*l"oPgr"t '/rhcn sprtrnckrurrrlt?he. LACERATIONS, (MALLORY-WETSS SYNDROME)

E Witlr failure ofrelaxation, the refluxing gastriccontents junction overuhelrndle consricdon at gastroesophageal leadingto massivedilationandtearofstretchedwall

tr Longitudinal tearsin esophagusat tle esophagogasfic junction

O Morphology: junction, orianted - Longitudinaltearat gastroesophageal parallelto lumenof esophagus - Varies in length(severalcm) - May involve$e mm or perforatetlre*all. into tlremugins (accounts to 5-:0% of - Hemorrhage upperGIT bleeding) (ulcer.mediastinitis, - 2ry mlecholon empyema)

precedes the antiperistaltic wave of contraction. D With failure ofrelaxation, tie refluxing gastric contents overwhelrn fte constriction at gastroesophageal junction leading to massive dilation and ter ofssetched wall

cohnrnofla{eohotis

-Srlgur4fion {gtua,

r e*nf!,

Pup+cuaLrioVs:

ESOPFIAGEALCARCINOMA (l) Squamous cell carcinoma(9004) (2) Adenocarcinoma

esofifiws ru x a

furyror 4fPtort

rX"gt*) inf,.fion Rsdiogmph showing squmos

cell wcinom4

| -216 oFeA dlr{ns It

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Xr'Ptfom\$tl''it''

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,r,' tf ,!1:n"" hnf -ufl#'^r"t ^ flW"nt ehawpi"

bJ$lcohol*srrutr!) , lnilahm c) tlPv,+4rr,oresoPhYln/-" ,

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inhib* Tinofiptsor

4+"^aff Orcnync 6

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Sttl GASTRITIS ACUTE GASTRITIS Acute erosivehemonhagicgastritis- altAtt

Transient inflammation of mucosa, maybeaccompanied with (erosion) hemorrhage sloughing or evensuperficial

n4tfo$P4rl

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Pathoeenesis: triEili"no* ioitantstlo8l in$. ca44/' - Aspirin,NSAIDs - Corticosteroids alcohol, heavy smoking - Excess (accidental ofcorrosives or suicidal) - Ingestion gk6;fii|f(2) StresJulcers (traumgsurgerylhrtnt. (3)Hypersecretion of gastric acicf

*

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uttsfl;n

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Stomach, nomal appwmce of ftrndal mucos: short pits (lined with pale olmnu muu ells) leading to long glsds ( with bright pink cells that wrete hvdrochlori

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(4) Impairedprotectivemechanisms: muoussecretion, decreased deficiency of prostaglandin

\ l' ' FFhryn

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wrt

Slrrpk,oosivo, Yemwtlli t'

Acrtle' lnflanu*utt

Pathology: - Widesprcadpetechialhemorrhages - Mucosalerosion:sloughingofepithelium-+punchedout ulcers - Mild inflammationwith neutrophils - Healingwiftin few days Clinical: - Vagueabdominalpainunlesscomplicatedby massive hemorrhageor perforation-r Petitolitt6 - Acute gastritisdue to NSAIDs may show hypochromic microcytic anemiadueto undetected bleeding

.rqni$tl - cr$*fi t rmr Mrrv4r Avrcliaot&qfid

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Chronicinflammatory diseaseofthe stomachthat variesfrom mild superficialinvolvementto s€vereatrophyandepithelial metaplasia

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ohvovrro %q*"

(t*.rffiedeg$iit$ - Autoimmune process,presenceof antibodyto-ESjgtgl cells& intrinsicfactor - Processrestrictedto fundusand body ofstomach (not to the antnrm) trlqrgl@

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A*VoPhgoFrnacrrt mtar ln I

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Wvtdl nilt4usvb6g Notcrrvrrnan.

(gf .Iiiif€GtidMhdi,€CIbc.teq*."",r"'i.. - The most commoncauseof gastritisin USA - Prevalenceof infection increaseswith age,at age of 60 almostall populalion are serologicallypositive,2l3 show histologicalevidenceof gastritis - The organismremainson the surface(no invasionofmucosa) - Chronic inflammationof antrunt andbodv

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i,

- Playsimportantrole in pepticulceration(all casesof duodenalulcersand% with gastriculcers) Increasedrisk of cancer ar*

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PEPTIc ut-cEn's- d,i srupt'tt<' '1

(l) Intedinal netoplasia, the gastric epithelium is replaced by intestinaltype (2) Dysplasia:cytologicalalterations(shape,size, orientation, nuclearenlargement)-+ increasedincidenceof gastriccancer in chronic gastritis. (3) Degeneration ofthe epitheliumofgastricglands-+marked reductionin their number(alropftic gastitis)

. Mucosalulcerationsthat gdend tkough the epitheliallayer into the submucosaordOeper. . It may occur in any pan ofGIT exposed!o acid pepsin,most ofteninsomachan-l:4t. . Incidence:in USA,2.5% ofmalesand 1.5%in femaleshave peptic ulcers

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. Age: Duodenal40-60years Gastric:middleagedandelderlymorethanyoung

(4) InJiltation of the macosaby lymphorytes and plasna cells

Nver{rcrrltrm Ittt4 ocur il ewn Heeh'l's

fs"rro{*r

h,rS,brach PrulecJrva papilcrrlcrrs .L Pathogpnesis::

Pathoepnesis::

lmbalancebetweenacid/pepsinsecretionand mucosaldefense mechanism: f Hypersecretionof acid I Decreasedmucosalresistanceto acid.

Imbalancebetweenacid/pepsinsecretionand mucosaldeGnse mechanism: )> Hypersecretionofacid > Decreasedmucosalresistanceto acid.

Normally stomach protecs itself from self dige*ion by: (l) mucussecretion (2) HCOPsecretion (3) mpid gastricepithelialregeneration (4) rich mucosalbloodflow-+ sustainsthe high metabolicand regenerativeactivity (5) mucosalreleaseofprostaglandin-t maintainsmucosal bloodsupply

Normally stonmch protecls ilself from self digestionby: (l)mucussecretion \ -- .

: lli[88t;::lX-v,*uot.o ac;^7wee (3) rapidgastricepithelialregeneration (4) rich mucosalbloodflow-+ sustainsthe highmetabolicand regenerativeactivity feplf ao ar€ t-f,d.c.{:. (5) mucosalreleaseofggEglgglgr --+maintainsmucosaF

bloodsupplv ffia#*plr.

td jp.ltt4--

iftt\lwr.,ffi, th ednfod talsgNao.

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AggressiveFactors: l) Helicobacter oylori,inlaCrkOn - Isolatedfrom gastricantrum of 90%ocases with duodenalulcer and70oloof gastriCulcer - Treatrnentwith antibioticshelps healing& preventsrecunence. - Role: a) intenseinflammatoryresponse, Chrg|li c' itrihlionf

bjendotoxin - digr wyti cn slrfto

N

cPi.tti"rliutfl

c) urease.breakdownurea-) ammoniumchloride dj proteases& phospholipases + damagesurfaceepithelium e) stimulates acid secretionby promoting gastrinrelease

+ 2) NSAIDs: suppressmucosalprostaglandinsynthesis+ reduceHCCP and mucin (aspirin,ibuprofin had adverseeffect). 3) Cigarettesmoking:impairsmucosalbloodflow andhealing 4) Alcohol 5) Corticosteroids

Jblcods'.fpy e

0 in&h{hn4n"n

6)Psycologicalstress - {-/t

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ensqr€o +H@a-

|yle^X)

Patholos.v: -$j@: lessercuwatureof stomach +

anteralregion mrera rggfon 17 t9rt L (Erlfutl T.lloric Antwn

l. rolrl,,rr -, Ist part ofduodenum (anterior or posterior wall) - {CiJl

-Sh4pq:round,2 to 4cm in diameter, sharply punchedout edgesand overhangingmargins -Depth:varies,superficialor deep reachingmusclelayer

Microscooic: a-necrotictissue- heCfot Cd.O-bne b- inflammatory infiltrate c-granufationtissue f,to-UnS+ +rcR I d-fibroustissueatthebase ofulcer -&tvl"a k \

Epigastricpain(l-3 hoursaftermeals,worseat night,relieved

byantiacids andfood k rru tL - W ndtaliA'

+d Srifn4lflc- cpjStn" ocide /aI lcdrnV -amfr

{2)Pedbration (5% ofcase!) (3) Pyloric obsruction,: libtb$i$

(4) Malignancy:rarefor gastriculcer(unknom for duodenal)-.

?jcfAerq - yri ld- avrevnta ot c)TDntc -

ulcevr;$*e*

gPL'L2n nn,o--t

TQ ' |Atte"sottnts T 6asll ic or

I (,eVYu( cASrRrc rr.rMoRS lntestinalvariant

Diffusevariant

Origin

Gutric muou undergone intestinal metaplaia (chronic satdtis)

Nomal mucoss, not ssociated with chronic

Incidcnce

Moreommon in high risk prcple,diminishing in fruumcv in USA

No significant change in incidence over years

Dcgrcc of

Bener differentiated

Poorly differentiated

dilfcrentirtion Age incidence

ARer 50yeus

Euliv

M:F orcd(

2:l

Absent

age

Patholow: B Threemacroscopicpictures: (l) Exophytic:solidmassthatprojectsinto thelumen (2) Ulcerating:shallowulcer,l-10 cm diameterwith i induratedmargin (3) Infitrating:no tumormass,the entirewall is infiltrated, thickened(2cm),muchfibrosis,firm (Linitis plastica,leatherbottlestomach) r.to Stifhta lzfififi. D Microscopic : the pattemvariesfrom well differeqf4lpd o.rn**rn--.muoutryanaplasncntmor. Some produce mucrn that drsplacesthe nucleus\

t1

Ur*b(A, ntrt(qfpn+ Iu*tor o[+tv s+uilrr& hO-lSZ; -Vvtfrlcoyyu/lo1 ' 37" pl atl cau@{ert1",vls in4Sfl

&.

Pylorust cuttln$) 5q" C&d'ncend

fr*rilus+bY Z rnuprrsrqica.lType-s of ( tl.pllorf, pvgatfu ,s{tbkQd M -..) ' fntG'hy^d.I Vr'#r+ : onlppw,a@t6A - fu$It,c: fh pYelt
2'qo

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snread: pqrchdh"nll feacVxrgsmea{(l ) Local:nearbv orsans.ovarv(Krukenberetumor) (2) Lymphatic:regionallymohnodes(portahepa,along curvatures, distallvmphnodes:supraclavicular (3) Blood:liver, lung,brain

ogry).gi+gt4lunhrxd 4abd'h anneeI og v

J^fpdhtDy'uun-

saC peritoneal rnatJmn+Ascihs- sirdn2ttcsettt.i"lfit'r't*

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Clinical: ( I ) Non-specificsignsof tumorgrowth \rlt I 0e6 (2) Localsigns:vomiting,dysphagia,pyloricobstruction (3) Ulceration-+bleeding (4) Diatantmetastasis: supnclavicularlymphnodes,ovary

gc.rqdatf es h'vct,bran,tr

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ths

W*d"rruch

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,tw: villi+yk Colul/lnor [P3"3I"t..t".i Nomal appeme of smallintstinal muosa with longvilli havingwruional cells

virricow^d b1 mmvtur

w^

m.f; Longitudinal smooth muscle of colon 6 bmds, taenia @li

DEVELOPMENTALABNORMALITIES Mesacolon: distension ofthe colon more than 6 or 7 cm in diameter:

(l )goneenitalmega.colog (liir$spryne dise?se): SuIUC mcfal oI olstalpolttonot colon(rectum,seElnotd)- LacKoI tnnervanon + aganglionic segment - fu nctional obstruction - massive distention of colon proximal to affected segment - wall thinned (distention) or thickmed (muscle hlpertrophy) - delayed passageofmechoniurn. followed by vomiting. - complications: enterocolitits, perforation of distended colon

,ndrtib Fat sqrrcn+ aqniilalc PfD{tmal AnmakA

ltlkc*t6n

(2) Acquired mega colon: a- Chasa disease:hnanosomes directlv invade bowel

b- Organicobstructionby hrmoror sficture

Mu@sal crypts with mily goblel ells, submu@sal

c- Toxic mesacolon(ulcerativecolitis) d- Psvchomotor disorders

fe

-

rnd$qws

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svqtri! atritr')N

atnl,4{

+.lt4rrt\nd tu*.

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(l ) Arterialocclusion(celiac,superior,inferiormesenteric fieries) a- Arterial$ggglgsis (severeatherosclerosis,systemi

b-d49rj4.g!@ derached rhrombus from,lg<gg.c. le&Atdlrtl' "Hal fibrillatibn, LV 61766 -

- muralthrombusin pewiousmyocrdiai infarction. bacterialvegetations

th['htf

a&trrnunc dsgc*s

aodlic,un*FaJ

lfnchsprung disme. Contrastradiograph showingmokeddilationof reco*gmoio

c- tntrinsicvasculr lesion: - volwlous - in$ssception hemia - stangulated

EEvE BloryA A^st',a' U$6hu'st ffurkchs ';nt^(6q larasgt$ylt*o:

pr;iffiIattaw'r1

s'+*"[;%"^,M +nrlsco Clltlllz AWd)rq' @w t[z fyat$trrgo

lepEd!,V

- fdrrnsioVre'tilwWra*<'.

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(2) Thrombosis ofmesenteric vein: hyercoagulability ofblood by oral contaceptives,intraperitoineal sepsis, post-operative state

ffi,,,*d, br*|-ttta verufrs

(3) Non-occlusive ischemia: (intestinal infaction withoul occlusion): reduced cardiac out from shock, acute rnyocardial infarction, vasocontrictive drugs PaftoloeI: (l ) Severity of injury varies fiom: - transmural inftrction (involving all layers), - rnual infarction (mucosa and submucosa) sparing tlre muscle - mucosal infarction (not deeper than musculais mucosa)

(2) Infarction is always heirronhagic (3) Muked edema, interstitial hembrrhage, necrosis, gangrene Clinical: -Most common in later years of life - Suddm onset of severepain -Bloody dianhea

\i

Diarrhea: stoolmass(in excessof250 gm) or stool freauency - lncreased or stool fluidiry - Over I 4 liters may be lost /day in severecases - Often accompaniedwith pain,urgency,incontinence painfuldimhea,sraining,mucusandblood D)'sentery:

Ishmic

Recfteller;iml awde& Q
6tqitis, sall intestinal muosa with advmced nrcrosis . od acute inflmmation

{blusons*{lon- Sftaj (x: arfiraribfs+ bOciffic

@,li

rNFEcrrous ENrERocolrrrs cdn' - Dianhealdiseaseofmicobialorigin for onehalfofall dea6sin children - Worldwide,accounts youngerthan 5 years cliarrll1 ie9?*i5,ita<. SbL

- excessive omotic forces exerted bv luminal solutes- abatewitl fasting (e.g. Mg SO,.lact1rt.lr'i;-iA@ WL

(3)Ixrdativedia$hea: idtAnmOfrnlin[i*la

- Etiolog-v: (l ) Viruses:rotavirus

- outputof purulentbloodydianhea ?Fbjld tl - persistson fasting(e.g.shigel14mpylobacter))ftpgfil hs.d (4) Malabsomtion: #

(2) Bacteria: Enteropathogenicstrains of E. coli, salmonella. shigell4 campylobacter, vibrio cholerae, 4U clostndium difficile, clostridium perfringens -(3) kotozoa: Entamoebahistolytica, Girdia lamblia

- bulky stool with increasedosmolaritl'due to mabsorbed nutrients and exess fat (steatonhea) Dlfr+utVncr'

- usuallyabateson fasting (5)..+ii!frJ Deraneed motiliw: .,

- variable, diagnosedby exclusion of other tJ?es (e.g surgical

I

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&&chued4ahn1 4brprnot^ hd'

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- E.6li: norfiat fuq,-hafifil*S but ttr.lnre pdlrrynio $ains rdqrs

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* Intestinalabsorptionis characterizedby t\a'ophases: - Innalurninaldigestionin which proteins,crbohldrates and faS areenzlmaticallybroken down, a processtiat beginsin the mouth md continuesin small intestine. - Terminaldigestion:_ly4lgbgilof peptidesanddissacharides by peptidases anddisaccharidases in brushborderof mucosalcellsin SI. - Transepilhelialbasportofnutrients, fluid andelectrol]'tes acrossepithelialcellsof Sl

d$tf,

urdrrSg./r 0Sctt'de

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inlcrttulgurr&n

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qe= {-: Malabsorptionoccursdueto: Imoairedinnaluminaldieestionof food:

E Clinicalconditionin whichoneor moreirnponantnutrientsare inadequately absorbed from the srnallintestine.

ar irr&$u4

Una'blG$ dtlC*

&g1gfiffi"rio-n

no 7'

- Deficientbile saltssecondan'toliver diseases

Impairedabsorption: - Diminishedsurfaceabsorptiveareaof small intestine(bowel resection) hnr({,S htbf Unhcff{ul e.g.Iact6seinlolqllr,ce'- I IA6{6f,,O - Defectiveabsorption . - Damageto epithelialcells/ S Clinical: ofbulky, fiothy, greay, yellowor graystools - passage flatulence - anorexi4abdominaldistention,

rvasring _W. - muscfe

W, dhhder4ol, I eAgna,

hrysfton W) - intalwnind.'u (&lrth4,sfvn@$, Wctrya", l

-

+ rA' dtq*l WJntoaltaa'rut udis*rh G wwsdd Viyeacchsrvd

tPb'Jtu*-,")

pro*crngq a,.q,. + sho4 chern di'F€fh&, il ... {e}/a"'

ior-ornlrztclgcstroa .lrk€d &rrttruy diEetton

3

q CI, +v\0

qs,

Ulcerative colitis Bodr diseasesarechronic.relapsingofunknou,n etiology

lesions(inflamedsegmentsseparated by ia Incidence:g1g!5$j!e more prevalent in USA, Grear Britain md Scandanavia * Age: at an1'age (peak incidence in 2d-3'd decades) * Ser:&Ej{gi slightly more t}rm males

-in{tsnnrd $scnq mrJaoEr *rlarerc.oEq'

(4) Lumen:atmosralu,ayst4ffi$y edernaandlaterby fibrosis(stringsign.thin streamofbarium,stricture)

r,ut*,.\ d Acl*e : ltrill$ notruNd\ e&na

t

'W

NM

ghi*usvAAl e;rr.nic,Arrrnis

(5)Mucosa: al$cl+ "a"tn'" - erly focal mucosal ulcers -+

later coalesceinto long

sementine linearulce@ - ulcersbecomedeeper+fissuresthatpenetrate deeplythrougl ue u'arrone-ilerosaffi sures@d$*itr - turthe, extffi

UorL tilgraL{b

w,

',#ffit ffilJr"ru'rummmtriM (6) Microscooic: - Cbronicinflmmation of all

-'--

J

-

particutarty in colon)+ IlCoplaSiq

- Nodular lynphoid aggregates'

V,JtNt

Crohn's dise6e: poximal ed di$al strictules in teminal ilom

Serln$- *fl"*

iwmur(-rns/|!'}Cd'

iritis, sclerosingcirot- g'tiij X Clinical: (l ) Recunmt episodes ofcrampy abdominal pain, diarrhea, fever (2) Bleeding

ffi

gh

$3.:

(3) Initialaftackremitwith or witlrouttreafinent, followedby (4) Complications: - inte*inal :lEiEEtqorgbullqldon -.$1g!qwifr otherlooFiiFintistine, bladder,vagina,skin - abdominalgbtcessor peritonitis md malnutritionwith diffirselesionsin SI - malabsorotion risk of malignancy(lesstlra UC) - incremed ..

:

Chrunro cfu,4L!ryY1$elfi

t rWntA,dry ^Y,Auw rnuc4slnb/

;*"JC"xail*ffWmM e -'PlWrr"W

PtJ4 PuitDnid'6,

.'CP\neAStt , ,rrril nk46Lv,lufu4Ylw, Ulvod. tt\4UCpnu}/-I-r

.,d

*{$w,{'

D' * Ctrrons {;+,s frt len+1 Q n Utc,,ratw-6 F]LCERATIvEflE

'7/loo,^>)

* Incidence: -worldwide more commo{r(inUSA than

*+Age: anyage(peak20-25),equalincidencein both sexes

(1) Siteof lesiort*iqi@*ewdF(rectum or rectoseemoid) -etr) (2)lnflammatio@t ($dDffiffiHkEhn lesionbeginsin rectum,extendsproximally in fashion for a variable distance (may be entire colon! -ggp15ig11913l r+t iume t ii

col.n

,'\%

(5) Mucosa:hyperemia,edema,easy bleedingwitffiffiffiEryti,i€€Sffi Isolatedislandsof regeneratipgmucosabulgeinto g@. lpseudopolyps,progressive mucousalarophy.

l8r.r,brnucoSq'GrlFrf, in nrucoscr

,nffarnntjv't

?e totvnalui

Wottno*a {o *x,c.s- il1*rs+t \otolostruchor; lota jrnstdrtr

(6-;Microscopic: ttntrun o{cpdlufiurnu/ * - 111fi n $,

'

- Chronicinflammationof'beBs*&.sdbmucosa - Iossandatrophyofsurfaceepithelim

Stluuilorro&atutc s Weryffi.ryS@Wry3$rlheanlky&i.srne spondylitis, sclerosine cholangitis)

-ffi* \\{./

X Clinical: (l ) Recurent episodesofbloody diarrhea with crampy abdominal pain, diarrhea, fever (2) Bleeding (more widr UC thm CD) (3) Initial attack remit rvith or without featrnenr. followed by

-.

Oran rltt.rr-'$ - C1'on'S

stury dnt+V MW

Buium enema:finegruulaity ofmucosa

1 Y.,r,,l

Diverticulum:blind pouchoffdre alimentaryEact,linedby mucosa andcommunicateswitlr the lumenof the gut., either congenital or acquired.

's diverticulum:d4oc{ (mucosilE6fiiiffiEi (3) Generallyasvmotomatic (4) May be sl'mptomatic when: - bacterial growth that depletesvitamin Br?-+ syndrome similqr

anem;aimocngl, toperniciius

uittcila:bb/o.ttr)

- contains lreterotropic gastric mucosa+ peptic uloemtion of adjacent mucous membrane.

uJanl,m atqah!'4

rt 6.lf

qwtoasd,

2- rnustrc.I gks a/cr,
o Acquired tlpe(Dive*icutosis): Vey C6yftmon in parallel rorvs taenlae

ffi7o), errvift

increases in frequency

age (50% above 60 years)

mtreased dlmculty ln passageot rntestrnalcontent+

sustainedbowel contractions+ increasedinfaluminal pressure. As nervesandvesselspenetratecircular musclein between taeniacoli they createfocal defectsalongwhish tle mucosa and submucosahemiate.

(2) Formedonly ofmucosaandsubmucosa hemiateddrough musclelay'er(pseudodiverticula), baseis fonnedofserosal tissue. connective (3) Number:variesfrom few to severalhundreds (4) Size:0.5-I cm (5) Gentrallyasvmptomatic (80%)or symptma&ri -i"t"-Grn--Trrping,continuousdiscomfortin theleft lowerquadrml - sensationofnever being ableto ernptydrerectum completely

le not covnpttcafion:

Yt"tUr*U.

(6) Diverticulitis: - inflammationofdiverticulum in responseto iritation causedby retainedfecalmaterialrq$ffirrhiort, pericolic pertonitis abscess, - Clinical: - fever, persistat lower abdominal pain - tendemess in lower left quadrant

Morecommonin smallintestine ? Causes:

{r Hernias: t46thq+ f0ft6dYlu[-ddr@ - Weaknessin the wall of peritonealcavity that permits protrusionofserous-lined sacofperitoneum(hemialsac), segmentofthe visceramay becomeFappedin them (smallintestineor omentum). - Pressureat dreneckinterfereswith blood supplv+ infarction - Sites: ilgualand

femoral cmais, mbilicus. surgical 5gggg

;/frndretopeitoneat

g$r

I

\

ffir

.-'.:

::1

Umbilica.l hemia with small hemial sc containing adipose tisue from omstum

segment ofbowel into the distal one - In chidren: due to excessiveDeristaltic activitv- and in adults

dueto a mass(tumor) ofblood - Compression supply+ infarction

s# +{

WdN

cffss

twIslU

TUMORS OF SMALL AND LARGE INTESTINES

q {

Majority of Intestinal pollps occur sporadically: - rnainly in colon - lncrease in frequency with age

ffi

J- 'o

lx

either single or multiple

Vohulus: uisting of mesentery, entiresmallintotine bemmes iscbemic,darkred fron infuction

*ry *#fi6W

aoM

nippleJike, 6ess'&digb:F.i1)tive cellsandgobletcells,

\tpr#N1

srHt'' Neoplasticpol!,p(adenoma):

8 b

- Very low incidence in dre small intestine, higher in colon - Prevalenceincreaseswith age (40-50% at age of60) - Familial predisposition 4 4X-. -figlL - Most colorectal cancersrise in pre-existing adenomas qrpes: -There are 3 (l) Tubular adsoma: mostll tubula glmds (2) Villous adenoma: villlous projections (3) Tubulovillous adenona: mixture ofabove

.

- larae uD to l0 cm in diameter ji9!s&, caulifl owerlike surface - fomed of finger-like extensionsof the mucosa, covered with dysplastic cells - cmcer is high (40%) in adenomasmore than 4 cm

Urlrgr Si1,t rf

Tubularadenoma:

-

-*$

- most conmon + pedmculated. slender stalli I -J cm long - smooth surt-ac-e- usually less than 2 cm in diarneter. - fomed of branching disorganized glmds rvjth tall hlperchromatic cells - cancer is rare in adenomasless than I crn{

br19n

Adenomat@s pollp (tubulu adenoma) with hemonhagic surface md long nmow stalk

fa

*J,t[sc$dssena-

:

v}@&.{*J

Tubulovillous adenoma: Mix oftubularandaveolarareas .

f'1a7.

clinical:

W

- as)'mptomatic usually

'"ryt"ai"" -ocetil+ lwr* +a'n, ,/

rr*wr,ltOJwrrr

a;rrrw*rc+ Lr. [bJ ,n<*r

b

iu I

.+;

..1

Villous adfl om4 sessile, larger thu tubuld adenoma (up to I 0 cm)

Adenomatous polyp (tubuld adenoma): small stalk, crowded diprg&iad gluds lined uirh cells havi nuclei, less goblet c€lls,

CLORECTALCARCINOMA

- 134.000 cases/yearand about 55,000 dea$s in USA - Peali incidence is 60-70 yeus of age - More in males - Adenoma-Carcinoma Sequence: (l ) Populations having hilh prevalence ofadenomas have a high prevalence of colorectal cancer (2) Adenomatous pol]?s antedateb), several vears onset of colorectal cancer (3) Patients u'ho are followed and rvho have all adenomatous pollps removed are art decreasedrisk for colorectal cancer Villous adenoms:@liflowerlike covercd with dvsoldtic eDi

due ro elongred gludultr structures

(l) Polypoidal rnass (2) Ulcerating (3) Infiltrative (mnular, constrictive) Microscopic: adenocarcinom4 well differentiated Spread:local, local llmph nodes, liver, lung, bones Clinical:

- Change in bowel habits, abdomilal pain, reduced stool caliber

Cilcinoma, lefl coloq onuls, encircling od onstricting heapedup n, ulceEted

10

Adenocilcinom4 neopluticglads with crowdednuclei,plsmorphism, hyperchmmtism

11

1 j

Functions: (l ) Processingofdietary aminoacids,ca6ohy&ates,lipids, and vitamins (2) S1'ntheses of serumproteins (3) Detoxificationandexcretioninto bile ofendogenousu'aste products,toxins, microbes Greatfunctionalreserveoftbe liver masksthe clinical impact ofearly liver damage Removalof 75% of liverproduces little changein function+ total resenerationwithin few weeks

@

Q,rtto11 ?olVt

fr Bile formationserves2 function:

(l) Bilirubinis dreendproductofhernedegradation, derivedfrom brealdown of old RBCsin mac.ggplggg( liver , spleen,BM).

(l) Eliminationof systemicwasteproducts:

(2) Bilirubindrusis fomed outsidedreliver+ tightlyboundto . . -^ . ^ j L j l : -. L : -\ .

- Bilirubin(endproductofhemedegpdation)

--

of albumin-freebilirubin is found in theplasma-r may diffirse into tissues. iii) Thealbumin-free fractioncanincrease in severe hemolltic disease, e.g.hemolyticdiseases of neu'boms (erytlroblastosisfetalis) + may accumulatein the brain + severeneurologicdisorders(Kemicterus)

- Excess cholesterol (2) Emulsification ofdietary fat (detergerit action ofbile salts)

Nomal bilirubin value: varies, 0.3-1.2 mgolo Systemic retention of bilirubin (more tlan 2 mgolo)+ yellow skin coloration Iaundice)

d

I (3) Obstruction ofbile flow (4) Conjugatedbilirubin in $e plasrnacm drereforebe excreted

Jaandiceoccuts whenewr therc is imbalaucebe*een bilirubin productbn and auetion: (l) Excessive productionofbilirubin 'l (albumin (2) Reduced boud) hepaticuptake I Un@njugated hvpeftilirubinemia (3) Impairedconjugation I

Physiological (neonatal)jaandice of newborns: Becauseconjugatingandexcretingbilirubin do not fully mature until about2 weeksafferbirdr, almostall newbomsdevelopsome degreeofjaundice dueto unconjugatedhyperbilirubinemia

[-

0hotes{a-t{s, oFuw WftA+oF+r*J(rr.) rS

i, Pathologv:

O Systemicretentionofnot onlybilirubin but alsoothersolutes eliminatedin bile:bile saltsandcholesterol O Results fiom frepatocellular dvsfunction or hilnn (rnEa- or extranepahc), presenled$1th: Bilirubin: Jaundice Bile salts: elevated bile salts + $eir deposition in peripheral tissues (skin)+ pruritus. Cholesterol: Skin xanthoma Elevated level of ohosohatase

alkaline

obs!ructrcn

- Similarin obsfuctiveandnonobstructive conditions. - Bile pignents accumulateu,ithrn liver cell - Bromish plugsof bile in dilatedbile canaliculi - Obsructioninducesdistentionofupstreambile ductswirh bile - Proliferationofbile ducts ofliver cells.fibrosis - Prolongedobsruction:focaldestruction thatextendsandsubdiridesdre[iverprmchma. finallybiliry cirhosis

r I HEPATIC FAILURE 0 Themostsevereclinicalconsequence ofliver diseases n Resultof suddenmassivehepaticdesruction,mostoften due to progressivedamageofthe liver n 80-90%ofhepatic functionalcapacitymust be erodedbefore hepaticfailuremanifests.

(3) Hepaticdysfirnctionwidrout overtnecrosis:hepatocytesare viable but unableto performnormalfunctions: acutefaffy liver ofpregnancy,tetracyclinetoxicity, Reye'ssyndrome

Categories of liver failure: ( I ) Massive heoatic necrosis: a) tumlnmt vra neDanns

b) Drugsandchemicals: = Acetminophen,antituberculous drugs(isoniazid, rifanpin), halothme,industrialchemicals(CC4), mushroompoisoning. : Eiher dueto: toxic effect,or hepatocyte destruction -tdirect 4f immune-mediated

€

G(impaired

t

productionby liver) vs tsu d l tL

u r ca L - vL r c,

- I- l u cr sL '

-i

Ull

\ot'*traf m*ftir' lir'rle o@ser -6-' mct\ ho$ rQffon=<-

I he tollowlns ls the heouencv of etioloeical cateeories

(3) Biliarydisease. s-10% Ur\\qF{ Crf rh06\S (4) Hereditaryhemochromatosis, iron overload.59/o

/uJ\r impairmentof diffirsion of solutesbetweenliver cells \ Ri* -disruptionofbloodflowmd + productionof inflammatory a) chronicinflammation cytokinesby Kupffercellsandendothelialcells: TNF, ll-l , toxinS b) directstimulationofperisinusoidal stellatecells(in space . of Disse)by toxins+ fiansfom ini66ffiUhsri;t =cells

/

Fffi*".-l fr (8) Sphilis

'

(8) C5ptogeniccinhosis-l0-l5o/o . v , r 1 ..^ -

\ttn nor b€ aYPeJL{ :6 rkGQgtrvn\Gir,j A i eanrres: E Bridsing fibrous seota, delicate bands or broad scars replacing adjacent lobules E Paenchrmal nodules caused by by regenerationofencircled hepatocytes,\,ar),ing fiom very small (< 3mm, micronodules) to large (several cms. rq3qronodules) ci c f hi?.,

scarringdoesnot constitutecirhosis. E- Disruptionofarchitecture ofentire liver

- Nonspecific: anorexia, weakless and u'eight loss

-r:

Progressiveliver failure relatedto portalhlpertension Complications

= I Liver nerosis + fibrcsis+ regmmion+ fim nodulr livq cinhosis.I

ia $^-L

,-aLa$ese \aW^ /

.] l:-/:

*n

Livtr ci[hosis: regenentivenodulesofiepatoc]ts surcuded by fibrous tissuecontaining settered lymphcyres & prclifenting bile duds

Clinical conseouencesto portal hnrertension

A F

excesslrurcm pentonearca\lly (2) Portosystemic venousshunts: - veinsu,ithin tie re"tuffi - velns aI ctroroesoDnauai_runcnon flfr-rz - veins along falciform ligament of liver and periumbilical - ' -^

andabdominalwall collateralsIIf, (J) Consesti\-t(increased

bloodu,ithinsnleen\

(4)Hepati[

lru1ngdc+lnliit{g rn b{ud

ry?Bpn^ INFLAMMATORY DISEASES VIRAL HEPATITIS HepatitisA virus(HAV): D Benign,self-limitingdisease

N

fishescoDcentrate virusin watercontatninated by hurnan

Cornrfun n hoyl$iluajs

* ctnitUren

^t#

w W

Khrciisnrt[hdbunt,? El Becauseviremia is transient,bloodbornebansmissoinof HAV is rare,so donatedblood is not specificallyscreenedfor this virus

Hepadds B virus rlIBVr,

[a

i Two billions are infectedtoday:757oin Asia andWestPacific In USA- 200,000to 300,000neu,cases everyyear. r

relDv6

Hdn4d

Mild or aSnnptomafic course E Virusis not cytotoxicto hepatoc),tes, liver injury seemsto be

crr(hcgr

i Canproduce: \) (l) Asymptomatic,subclinicalcarrierstate (57(2) Symptomatic hepatitis: l3Ja) mild acutehepatitiswith clearanceof the virus, recovery9C b) fulrninantbeoatitiswitlr massiveliver necrosis I fo c) chronicheoatitis: r rpr -asymptomaticcanier, recovery - activehepatitis:cinhosis,hepaticcarcinqna

/s DNO vlus ,

mvetqecl

i lmportmtrole in development of hepaticcarcinoma

\verColts- VrrrrSis prdent ro a) B[oDd

during the active episodesin acuteandchroniclrepatitis. Boft bloodandbodyfluidsareprimaryvehiclesof

Chronichepatitis(l 0%) (l) Asynptomaticcariers:recovery (2) Active hepatitis:cirrhosis, carcinoma . trvef ro{

Qcrl, rnitd

pcosl frsue ftn"as:B&Lrve

ggeftsn

l% At I

r

r

-r

,

(

Nuf rnSlootS. (unti re- ttp A.''y fiefbdes]:

n.,rfl

N.E.: {-\\,l"| | \rr Enlargedliver Microscopic: Multifocal areasof necrosiswith lymphocyic infiltrate of heDatocYtes - Ballooninsdeseneration ffif;illapente{

esinophilicshrunken

Virus is not c]'totoxic to hepatocytes,liver injury seemsto be

J

Clinical: rnyalgi4 nausea" vomiting - Prodromeoffever,headacbe, - Jaundice - Dark urine - Enlareedtenderliver

e-'S 3\tss (B): balloning Aote viml hepatiris

= baltotr|ry

Acute viral hepatitis (B): Councilmm body (necrotic hepatrclte), smsll cell with esinophilic cltoplam, pyhotic nuclei

\4ral hepatitis @), wiq

state;individual

Cwncr

Chronic adive hepatiris (B): mononuclw cell infiltrate in ponal tr6 eflends into adjacent Iobules unouding groups of hepatocJ,tes, mdy de undergoing degmeration md necrosis

lnflAmrtnfrun'

Potta-l tr aL+

ril

M0crcnodJ',Jo(qcaicl-iltan -.^

Sr'--r

I

. D] ' 'l('/

r \\

, r\{lr"( D.I.' r.k

uus;r,' sdJ" Fulminmt hepatitis, eKensive |l@ of nsrosis+ small liler with winkled capsule

-J i

E*"etrt

';:#1"'ilPs"

t tl'i-=----

neLrDes 6

ofi Atfllduqh trrni[eC,n d,stnrka"ul w

-_ ,J

flcpb tusn) 2b,c,0b-3s

Wpcltlo

HeoatitisC infection

.rtI|[|ni.n.|r.--.-.

":!@ - Majorroutesof transmissiffi Transnissionanong healthworkers andbf sexualcontactis exhffielyrow, $gyyrf g eS

-r

9f HCV. fligh rateof . - Penistmtinfectbn'is.gfudlfnark t "p-roqres:igltoffiiifr8ils1ma(59.70%) md cinhosis " X (2c"T5%)&al'*iBv r

-rp.:6-12weeks Shor*ef *han

I

Cintrosis (20-3s%)

II

I Hepatwdlulueinoma

f3

- Clinicalcourseis usuallymilderthanHBV" oftenaslmptornatic withoutprogessingto cinhosis - ChronicHCV for decades heoatitisis rue - Fulrninant

tc lruerdrVnsP 101' olurlo;:Chm{t ZO-s52. clrr ho9s

Y"3,nua

dd -u:hq ,ntl*Qarotr"{ lo'tu*"

ban\5n \iort fr +v a^.co-\lKc^

\Ab-g'

#patitispvirus(Hpv), Dgfec'ff Vg; VrruS U

.$+t

-Hepatitisdeltavirur -Defectiveviruw and acquires lIBs antigen coat as envelop)

.\*S" -

p - Self limited - Not associatedwith chronic liver disease

(ecAv(Jli

- High mortality rateamongpregnantwolnur(20%)

*r:r$rot

-ResemblesFiBV@

s

Hepatitrs G virus(HCV),f,r,,r, ,;;)\ AJ\k{by - Transmission

;SnontY

t.ttD \

a) contaminated bloodandbloodproducts,\',lJry.1U((r b ) possiblyby sexualconract.esp. horno SalH.clS

rnftc| do CCIn'l 'r Ut$= tts gl

,q. :.;.. _-,.;:..:.., i ,. - .. ' - Corirnronty infectspatientswith HIV. this dualinfection t "isrirttedfrxeaedN tfl{i'l.sT€(.ffitms}fivedtaffbt.): ,, i

*hii vi'ras

-du-nnot

|Ygtdtg

tt&es rrnrrurno

S'rppte*Dn

9,C,and> &rnr. ];-ransrnrsftoh

ancg

or,tTJli cLM

bFFl@V I

I"IAV

Liver abscess: E In developing countries: common, parasitic: amebic liver abscess D In developed counfies: uncommon, bacterial or fungal Organisns reacb liver through: - ascending infection in biliary tract - blood spread by portal vein or hepatic adery, - direct invasion fiom adjacent souce, - penetrating injury B Single or multiple, small or large (few mms to several cms) E Clinical: fever, pain in right upper quadrant- tender hepatomegaly.

mdjaundice &"tAa1rtt"

oq $tory tfcct

E Surgicaldrainageis oftennecessary

- is i\e rn4lormelabolizingmd detoxifyingor-ranin rhebody. lF Liver i*+hjury mayresultfrdm1l ) directtoxicity,(2) lrepaticconversion of (3) through immune mechanisms.

xenobiotic into active to\or

\

t* Drug-induced chronichepalti(is dlniq!ly andhisrologically simila to chronic viralpfatitis {e Serologicalmrpfs

ad auto)tnqlune hepatitrs

,//

-\

of viral infection ue critical for

-\\-

diagnosis/./r'

* e*p9sdf to to*in or $erapeuticagentshouldalwaysbe included iry'6edifferentialdiagmosis of an1,form of liver disease

I Liver,mebic abwss I

N \N;

ilih'

Alcoholicliver disease:

k-lrohsl thrl-\ L?'.bbs mt+e-hsrdna

$

f€-6ptrar\,yf larUn Oxd-

a) more than I

b) causes100,000-200,000deadrVyearin USA:

5rii- mostdeaths

resultof car accidents iii- 20,000dueto endstageliver failure

.1. Distinctiveformsof liver diseasedueto ethanol : ri- alcoholichepatitis:10-350/o l::*:::t^:H^"^l arcononcrrverors^e --ttiii- cirhosis:l0-l5o/o J I

- Microscooic:lipid accumulates, vesicularglobules-peripheral displacement of nucleus

QstustU,a,-ql-op'nqfS{ dcohol . .i.Dairr. ingestion "rl6rs#. l#,I",PryL lcvcrg udrrag. - , .;tIEt!!. 'rur€ - foci cellular su'elling and necrosrs, - inflammatory infiltrate, - fibrosis

ll d, rW e*h,slwcl W rylos-^)Qd

4"ha.4

,

tre

lhdr accr{muJc-ftry} +Crrfr"lerg'flI

Ta

b) alcoholcan bemajor caloric sourcein tlre diet displacing othernutrients-+malnutrition andt"itamindeficiency e.g.thiaminandBI2. bl c) impaireddigestiondueto dmage of gastricmd intestinal mucosae

Clinical findings: Fanyliver (steatosis): - HepatomegalyeMlAr^Nj, b-dlf - Mild increasebilirubinanil alkalinephosphatase Chronichepatitis: weightloss,fever - Malaise,anorexia, - Enlargedtenda liver. abdominaldiscomfort bilirubinandalkalinephosphatase - Increased

6pYgfi,u-te (.trrhos+i

2) Hepaticfailure

ffiF m

\,\eirsh*nLen "hbrosre

Uver cinfiosis.Numercusregenentivenodules,small(ess rhm 3 mm, micrqodulu cinhosis),sepmtedby depressed rm of scatissuqe.g. alcoholism. biliarycinhosis.hemchromatosis

Cr vr h o ? S . fy(tD S,*hrduJ6 23, t " " )4 nTt YY\a'v'p ho&deE *f*o**** Shc/-ld teoNt,\q *f61*a*wsd,

CrrfiaJv€-qn"{CISS rtl lrnluo}a Aloholic cinhosis: 0 Micronodulr o Regenemting nodules of disordered cord @lls, no qtral vein B Nodules sunqnded by fbrous tissue rvith chronic inflmmatory cells od

*'t.

'!tt-tor*a

' -^^"sn'!totl"utfl 6r\ Vo

1'41

INBORN ERRORSOF METABOLISM and PEDIATRICLIVER DISEASE (l ) Hemochromatosis (2) Wilson'sdisease (3) al- mtitrypsin cleftUeXt

@ I

C,/

R\l duet" qoo mil+ai16t) GALLBLADDERI

hr\ arxehi*-rt+delcnnrned ]l

fi.rloiorrvaj rAdtsstuc Chi r rrutS+ rcv. fU Wlo Dalc4"lf5

Excessive accumulation of bodl*+ organs(mostly irilfff

Excess iron is directlv toxic to tissues: (l) Stimulation of collagen fomation .-

OlC{Srve

^ hUfV-t

(2)Directinteraction predisposition ofironwithDNA+ lethalinjur1,, to carcinoma'henaj"C4 (3)Lipidperoxidadon' (Fre<_Dz R4dica-[s < dloNqa-.

deposited

Causes: (l) Prirnan,: recessive - geneticdefect,autosomal ironaecmulatesoverlifetime.

.

[b

$-,i w"

(2) Secondarv (acquiredl:iron overload:qi ven fe - boO.q rorl I O - prentral iron Ypla.? need-AH Ovrt f - trmsfusions J fo - hemolyic anemius- t€ tb allhq"t, fltxUlltrd utilization,e.g,aplu.ti" ao-.mia' btgs - decreased Crcf l

Patholoq.v: - Deposition of hemosiderin in liver, pancreas,myocardim, joint. skin, pituitary,. thyroid ..etc - Golden-yellow hemosiderin granules in the cyoplmm ofcells.

(75-80%ofpatiens) - Pmcreas:diabetes - Heart:interstitialfibrosis g - JEirlls:acutesynovitis'at+hn{a

v{-.rf

s - trbro€r

isj e',r"it! - hc dlpo? t' rn $hovr4-Qenlrr

(6) Hlpogonadism (amenonbea in females, impotence in males) (7) Earlier clinical presentation in males, physiologic iron loss (menstruation, pregnmcy) retards iron accumulation in women

loc4. pls coill dbrc{m

lwer* | a,r1e-n orrb€JS \J \e\€+s-

-A-"r|iniS"l""lilqrxqonaaisf,'.,

* Bncr,lnartcoloYaj;6\

A !'mplomalrc: I (l) Hepatornegaly. abdominalpaln-7 Shnffilt{'c (2) Diabetesmellitus(destruction ofpmcreaticislets) (3) Cardiacdysfunction(arrhlthmia,cadiomyopathy) (4) Skinoiementation

c<Jl'ot''uer

geJa.ceI\S elrabobs R.estnc"five CfprctrOfirlrr

Fo*L'€$

Liver.hemshrcmatosis, Kupfferells in sinusoids full ofbrom hemosiderin

qf+rr * Autosomal recessive disorder rfiptaholicm+ accumulation oftoxic levels ofcopper inlnmy tissues,mostly

-

* Nomal copper physiology: a) absorption ofingested copper (2-5 mg/day). "'t""'

b)Piplasma vr o Jr u a u 4 r JPu r "r f\ 54 ralsport. bouni"lburin c) hepaticuptake,bound to a2- globulinasceruloplasmin + blobd d) hepaticuptakeofceruloplasmin fiom plasm4lysosornal degradation-+ secretionoffree oopperin bile

* In Wilson's disease,absorbedcopperfails to enterthe circulation in theform ofceruloplasmin+decreased biliary excretionofcopl

Iiter uha-bL-,*o hak-Cu,UlaZ r r,

^vd4,oc!

f,+S*u'IaM ,f,- J tt'

-s.ryJ,$t'^*l'$ -.x$;$*). * Pathoeenesis: Increasedcoppercausestoxic liver injury: (1) promotesformationof&eeradicals (2) bindingto cellularproteins (3) non-ceruloplasmin-bomd copperspillsoverinto circulation -+ hemolysis,lesionsin brain,eye ... * Clinical: - Usualonset:6 years

t uru{

+l

*Treatnent: Long-termcopperchelationtherapy@-penicillamine)

Parkinsonlikemanifestations rings(browish depositsof copperin - Eye:Kayser-Fleischer Descment's membrme)

d409,,"r Ftk1fn

Wilwn's disce: accumulation of red-brommules of in liver. liver cinhosis

s# T*$ fDf groenb .rn\un'- kuf r"^ \\ Uet-

31n$of,be .v/

f\

al- antitrypsin deficiencJ faaOt -ngtd,gC tQ B Autosomal

recessive disorder, marked

by fte low serum level

ol 0l- mbFwsln ...,.'---:.>

B Main function of AAT

o Syndresized mainlyby theliver o Its deficiencyleadstoAf;(lack of this proreinpemits the activityof neutrophiltissuedestructin g en4m es)

rnkonS*Y*alsnt

-) e\cchooa a\ao:Bd

o The mutant protein can not be secreted by the hepatocyte, it accumulatesas globular inclusions ofretained AAD ( sbongly positive with PAS stain) o Clinical: -Newboms:10-20% exhibitchotestasis ) €arf - Older children md adults: ptesilt u,ith: - chronic hepatitis - cinhosis - emphysema

't

14{

bi €

Y-j

''\

{t Reve'ssyndrome

'cj'';(dteYt

. Rare disease characterized

. Affects chi -l-.

Ftr

trhlrrFtlarlC\n"Ch . Paftoeenesis: ' ' - Unlinown - Derangementof mitochondrialfunction in combinationwith viral infection.lI Liver: redhyalineglobulessined with PAS,alpha-l- mtitrypsiq the Droteinis not secffied.a@umulals ln

. Deadr . Adminisaation ofaspirin to contol fever in viral infections of children should be avoided

of

qounq

vinJ inkhlon kotrin tohrr#lrr \,hq? ural{ in6r0runu , ffir'hcludtd.)

Kesf mrDn

JI Jte

OBSTRUCTIVEBILIARY TRACT DISEASE

r€A.sbn Lnown - Prolonged obstruction ofbiliary tree - Causes: (l ) Extrahepatic cholelithiasistF (2) Strictures from previous surgery (3) Malignatcies ofofbiliry tree and head ofpancreas

o Diseasecharacterizedby: inflammation,fibrosis, inegular *-icnrresanddilationsofintrahepaticandextrahepatic bile ducts

o Males affected more than females (2:l )

- Early lesions are reversible with conection ofobstruction - Prolonged obstruction and secondary inflammation + periportal fibrogenesis+ scming md nodule formation (2ry biliary cirrhosis)

o Chronicprogressive andoftenfatalcholestatic liver disease. Non suppurative.granulomatous destructjonof mediun-sized intrahepatic bile ducts,portalinflammation& scming o Cinhosisonly latein thecourseofthe disease

(a!iPrinaq' biliary cinhosis: autoimue Mtahondial AB), chronic inflmmation in ds. bile destruction Donal duct

F*"ltrh.dblfi;l

losebile prmnlrn0 'fL'bqeV I.we tds, Fnrtochondrfl

- bepaticartery(40%) - portalvein (60) - Obstsuctionof&e main hepaticarterydoesnot alwalc produce ischernic necrosisof the organ.Tlrombosisof intrahepatic branch ofhepaticarteryby thrombosis. embolism,tumor+ mayresultin localizedinfarct. : -Portalvein obstruction - ascitis pressurein GIT - increased varices - esophageal

-hemrnorhoict"

wili

wh fubr

a

- Red-blue nodule, less than 2 cm below the - Vascular chmels. lined by endothelial cell wi$ interuening stroma (2) Liver cell adenoma: - Mostly in women of childbearing age who usetr tumor regresseson discontinuation of hormone -I;, - Bile-stained, well-demarcated, usually beneaththe capsule

fltD

wdnomq ffi

lJ

- Relativelyunconmonin NordrAmericaandWesternEurope 5:2o/oof all more common

(3) Dietar-derivell

from tle fungus

flams(moldygrains orpeanuts) * heq061s

J)

(4) Chemicals e.g. dloratmst

used{o Ctr}linebilant

- Pathologv: N.E.:unifocalmrosivelesionor multifocal(scattered nodules) Microscopic:hepatocytes arrangedin nestsor smallcords - Clinical: Hepatomegaly, bloody ascitis, fever, pain, weight loss

roE:nosis: 3-6monthssmival afterdiagnosis

- Liver is a common site for metastatic spread ofcancer of primarv tumors: breast. lung, colon

€c^rosls

Cholelithiasi#r* - Affectsl0% ofadultpopulation in Westem counrries.C6 - Most gall stones are silent (800/o),no biliary pain or stone

smooth ?ourrd.o{al' ffi;g"- bM 'cvgg{al5

,,:chslebysri6* in ftafffrthfn

Pathosenesis:

': Aimosl al.waysinassociationr*,itli:.gdlstones is waterinsoluble,renderedwatersolubleby bile salts - Cbolesterol md lecitlrins cosecreted inlobile.

Acute calculuouscholecystitis: - Acute inflmmation

- Prevalenceincreaseswith: a) age (30oloofpeople older than SOyears); 5 b) in native Americans (?5% prevalence)

of gallbladder that containsstoneg

oiirifr onit1446i:'!,0fii9nE$&ti of t$FMoift s. ?

c)2:l whirewomen versusmen -toC lUf pdCJ mOfCC gallbladder c)decreased motilit,_ blO b0(dnd b ClL. jaundice Clinical:signsandslmptomsof cholecystitis, sometimes

- Acute calculous cholecystitis is due to chemical irritahon and inflarnmation ofu,all associatedwith obstruction ofbile outflow - Acute acalculous cholecystitis (no stones).most casesoccur in seriously ill patients.

gh0lr'ldft. mrnlcolro+ Rr4tl/t+

,8\B Paftologv: - Enlarged gallbladder with red edematous wall - Serouscoat covered with fibrinous or even suDpurativeexudate

.qpp-_ctrlwp.,ii,eiaf.ptiti.radidt'hgrb shostetir;ndiich; rt - fercr, nausea regionis tender,rigid, sometimes distended - right subcostal gailbladder

Sm# ofCIbrtrrn ,Vojrn

FH3

iWadcd

,rMnd anrcdrry7

g6n6

peY

W

$'ith s'ift gall stones.Stonesdo not play - Almoslalwaysassociated a directrole in initiationof inflammationbut supersaruration of bilepredisposes to bothchronicinflammationmd stoneformation. - lnfections (E. coli, Enterobacfer) in l/3 ofcases.

Clinical: similr to the acute: bilitry colic, upper right quadrant pain, epigastric distress

44btw'

W

presence Choledocholithiasis: ofstonesin biliarytract Cholmgitrs: - Acute inflmmation of the rvall of bile ducts. almost alwavs due lo baclerial infection. It ,"iit6*y lesion obstructing "bile florv. most cornmonly stones (choledocholithiasis). - Bacteria enter enter Yia sphincter of Oddi, rather than blood:

^

'ffi5

\ilPrasitic

')

moffrrnpf. i;."*1.,,f t

KteDsteila Clostridium Bacteroides Enterobacter GrouD D streDtococci

infeclions in certainpans of the u,orld: schistosomiasis

r

-.^t-

l nr..^-.

-rr./

NMgS

@WN'YI

tumors:

W At*

- Cancer of gall bladder is rnore colnmon thil catcer aising il bile ducts - Slightly rnore cornrnonin rvornen | -

- occursmostiiequentfy ril1-i . decaae-

plOlglffi

- Diagnosedlale. 5 yer suruival rate ofonly | 9/o

U

.

|I 4

\YdYatalo'-ro0rwffi€ ' l,/

r

AcutePancreatitis: Ve8/ g1n'fiLs

ffif

'

- Enzlmaticnecrosisandinflammationofpancreas - Releaseof: faqv acidscombineu,rthcalcium - lipase-+fat necrosis, forminginsolublesalts -+ damageof pancreatictissueand - Foteolyic enzf,mes pseudocysttnecrotic - Pancreatic materiallined up b1,fibrous wall. no epithelialtirun\

fl fI i I

MC-

[to.l"r-nU hrrnefl

ehvahd

Sit4

It rnt*rlin

.fl"Jffi

-ifts

"'h"t^Sd,thdl

so7s Aore pilcretitis:

swollen with uas

of hemonhagic ncrosis, loss

h,sh 6c WhoJtl

I dJGUd

I Lrge pancrqtic pseudoc-vst,opened, with inegular brcm inner surface I

I

W;

w$QQItU

'cfu1py chronicpancreatitis, Qilftc at ampulla of Vater ii. Alcohol: strongpredisposingfactor (unknown mechanism) iii. Acinarcell injury by viruses,alcohol,toxins,trauma,

-A9Es!3939\. olsi]dJeleleEc.j4blosuq!--+ lossof parenchyrna + replacement byfibroustissueu,ithalcohor abuse'aCrfraqg O$OCfffOfCdlS. -Associared fibroticorsanwithextensive atl6Dhv - Densely -ctrnrcatT-

t+ Clinicalmanifestations: i. acuteabdominal:epigastricpairi r.adidtingto upperback(d medicalemergency) ii. peripheral:vascularcollapseand shocti$iiffid'.6btictiel,rlbntsge hli8'ieleaseof vdsodilatitg'agents)A Sh oC&

l) Persistentpain in the epigastricregion 2) Malabsorptionand steatorrhea 3) diabetes(latecomplication) 4) predisposition to pancreatic carcinoma

40FU €^ef

iii. Elevated seruni level ofamvlase and linase

glucosuna iv.Hl,perglycemia. dapgtlg

W

cnr*ihon

O f€l!t6

v. Hypocalcemia: calcium binds to fattl abids in abdomen

F,+' trrcyedlc

o,llumovrtmcl-thrb

o? S

r .P\

b*nitD

-lr

0rnbfnl Dl b+ + Ca+vgonDU S Carcinomaof the Pancreas:

rrs

(precededby lung. colon, breastand prostatecancers) no - Risk factors:? Smoking,? diet,? chemicalcarcinogens( evidencethat alcoholor coffeeincreases the risk) - Age: betrveen60 and80 years - Malesmorethanfemales,blacksmorethanrvhites - Site: r 60%O,inhead oflxiirbleas,I 5% in body.59zo in tail. 20olodiffirse

[h*

rw

- lLE.: induratedmass .u.i; .i'it.."nou,"@$[E# - lvircroscoprc:

l{€ad.,fruGtft1 wnf sili: lslvuer
(,Autgcera'

&ng' ffi$e affits

antigen,CA 19.9antigen - Bloodexamination:carcinoembryonic carcinoma) {gold markerfor Dancreatic

-#Tuw6ru'a.f

(iEs

tvl-rrdtDrer*''lo

lr^|^..I

..l lFv '

I l-

r

L vn

.a

IJ

[im.9+

.{\\\,,

nl\ f v l- r

I

eAh

f

\. - l n .

n lt

U, rcAktkath

r)

h- (encer l " ' - \trnXTrta !a(qatt'

ini pro::!r*c

\{g"Let

)-

8,

d\ r ' -JI

\\

\-

I

I tl

e #orn

CA bod'{ and+df rr Lqrnilnhc,

WwU

ffi

Q'+ eo[Dn

s +h p0'r-,Cf$-t3

.t}os

haWS gvx!*

ENDOCRINE

Diabetes Mellitus

Tlpe I VersusTypeIl Diabetes IDDM (TypeI)

NIDDM (TypeII)

A groupofdisorders thal affect many organs,characterizedby glucoseintolerance. abnormalities of insulinsecretionor metabolismleadingto hyperglycemia. glucosuriaandtendencyto developatherosclerosis. nephropathv andneuropathies

- Foundin lessthanl0%

leve,l atrl

PANCREAS

Jexceeds

Type il Di abetesMellitus ({rdE+irisli.ltsdepeitdcnr +I4EDlv4;1littd#6ffiEtSM)

Gt - Immunopatbologi"

mechanisms

- No HLA association - Foundin greaterthan 20%oftbem l -N one I - Insulinresistance

| "gryfi141eq4.51rybe

banal*ula.deg'-rcilltr0c8r.rna-

+" sf#,v**p$o * fl +r,,ryFlapsta ruf$o

Type I VersusType II Diabetes

(\pal_r

IDDM (Type I)

Swrj.on\\O -on:el1 in3u\in

- No insulitrs - Focal atrophyand amyloid - Mild B-cell depletion

Trearmenr

l- Insulin I

Weightloss | | -Oralhypoglycemic

I Insulilis ofan islet in a patienr who dweloped Diaberes mellitus I

dst'*s5,f'f,

{0Y,6\.Je;qp \_-/.J

_A

$r** v)

Pathogenesis of MetabolicDerangement - lnsulin is a major anabolichormone - Derangedinsulin fimction atrectsglucose,fat and protein metabolism - 1 glucosein blood -+ t glucosein urine (glycosuria)-r osmoticdiuresis(polyurea)-+ intensethirst (polydipsia). Increasedapetite(polyphagia)developscompletingthe classicdiabetictriad

=-

- OIIIUSetn|cKenlngol basementmembraneot caplllanesOl skin, skeletalmuile, retina and renal glomeruli - capillariesare moreleaky than normal to plasmaproteins

l,nlc6tg'[" ..-zndrno$ Grmnttt"?

*rDi'dd&tr,Mtlti6ls:' - occursexclusively iarype trd,iabetes - severeinsulin J and t glucagon - excessivereleaseof free fatty acids from adiposetissue - hepaticoxidation generatesketonebodies - !$q!em!a and-I@ruria systemicmetabolicketoacidosis - life-threatening (Drr'a . ct;a -eki<

- complicatedlesions(ulceration,calcification, hemonhage, thrombosis)lead to narrorving,occlusion,ischemiaand dilation aneurysmal large vesseldiseaseleadto myocardialinfarction cerebral strokeand gangreneof lower extremities

c-aD. ol&olanlvs

5D%MI d-ta*Ls

n

ft 3, Kidney: n€Phr$$: - Diabetic Nephropathy,kidneysare the mos severelydamaged organin diabetes - Renalfailureis a majorcauseofdeath a. Glonterular involvenpnt:

4. DiabeticOcularComplications Visual impairmentandblindnessdueto: .-a. diabetic retinopalry; hemorrhage,exudates,edema,thickening of retinal capillariesand microaneurvsms q.

Cataracl

gGtaucomat{€ngrttrh u* eYe 9[c- el$lU.t Resultin progessive proteinuriaand chronic renal failure b. l'ucular * arteriosclerosis -r nephrosclerosis andhypertension _ c. lnfecrnn +pyelonephritis St!t{6€_ neAiAh #

\or -'n{oc{irrr--.

t-

&uc\6d'hn

- symmehc penpheralneuropatiy - affectssensoryand motor newesoflower ertremities - Schuanncell injury, myelin degeneration - axonaldamage - autonomicneuropathymay lead to: * sexualimpotence * borveland bladderdysfunction

- cxqenssof Fanoreas - nqsultn etfu - hn+i Islet cell Tumors: - rare comparedto tumorsofexocrine pancreas Betacell tumors(lnsulinoma) qdOfpn"C}* - mostcommonisletcell tumor - producesufficient amounbofinsulin to causehypoglycemia - attackswith serumglucoselevel belorv50 mg/dl. - synptoms:confusion,Iossof consciousness \r1p64\r;CXim - aftackspromptlyrelievedby glucosefeeding 'r -

t 6Ul : aettfwle)tur^or

t cunow cudruU fl's arrlaq.nrzB ing^tri t)

r K

i '.-7aul

Acute mastitis: D Bastenasnter tre breast6roush.

=Gt

- Fissuresin the nipple during earlystageoftrursing i . Variousforms of dermatitisinvorlvingthe nipple :

Dl-'tt-l i;\RTr *.x_N_ti,\!t1l

cl Staphytooo6d'iilfecrioil.ill-derecs€iitshr6rbq,lwjbEieli*d abseosses-'+, tpipal infl [email protected], hgding mgy leave scamng

Mammaryduct ectasia(dilatedjlU9l5): o Nonbacterial infl anmation of breast o Dilation ofmain excretorv ducts.

o Rupnne of dilated ducts + chronic inflammation o Seenin multiparous women behveen 40 and 50 o Mistaken for cancer (palpable paiareolar mass, induation of breast,nipple retraction and thick white nipple secretion)

Traumatic fat necrosis I Uncommonhistoryof prior fauma . Localto onebreast . Centralfocusofnecroticfat cells,suroundinginflammatory reaction,later replacedby scartissue . Palpablemass,skin reFaction

Irumatic fat narcsis: inegulr far cells without psipheral nuclei, interuening pink morphos

nffiic

matsial ed inflmmdory

ells

JI -

morethanhalfofall surgicalprocedures on breast - Age:2040, rre aftermenopause - eggsc:hormonalimbalance: Excessestrogen Deficient progestrone Oral contraceptives decrease incidenceby maintaining balancebetweenestrogen/progestrone

{} THREEFORMS: women) + increase in fibrous stroma and dilation ofterminal ducts into cvsts,

no epithelialhlperplasia (simplefbrccystic disease) -(60-80o/oof -

Cvsts: -Multiforal,bilateral,vary rn size( l -5 cm), - Brom to blue,filled with serousfluid drarmay calcify ( microcalcificationsin mammograms). - Linedby a singlelayerof cubicalor columnuepithelium (multilayered in focalareas),may be largepolygonalcells granulr esinophilicc1'toplasm with abundant similarto sweatglands(Apocrinemetaplasia) surroundingall formsofcysts

oftminal duds + apocrine metaplciaof epi*reliu I | (l) Cysticdilararion (2) hcreed fibrcusmma | Cystic cheges: duct ild dudules bmne dilated. oithelium cuboidal

ta----rl

DFrcr&feradie'6lia$ses: r - Epithelialcell hyperplasia,frequendyaccompaniedby cystsandfibrosis. - holiferationofepithelialcellslining thedilatedterminalducts -r multilayeredwith papillaryinfoldings(ductalpapillomatosis) or filling the ductallumen(fenestrations) - Mld h'yperplasracaries little riskof oarcinondtl.5-2 times), at5pioal,.hyperplasia{cells varS'ingin sizemd shape, hlperchromaticnuclei)hassignificantlygearer risk (5"fold.inu€aied rtdk of oareinonia) i

Mar*edducralepirhelialhyperplcia, witft increreedrisk ofbrut crycinoma (1.5-2timesnomal)

Fibr@ystic chages, duds with epithelial hyperplaia (mulrilayered), no atlua

A$?ic€l dudal epithelia.l hyperpl6i4 (5-fold)

with increued risk of brut

cucinoma

& B SclerosinLadenosis: - Lesscommontha dreprevioustwo \pes eNumber of aciniperteminal duct mit is increased at leasthvice, backto baakfdd€roslg. ; - Markedintralobularfibrosis(sc/erosrs./+ rnaycompletely compress the lumensof ductsmd acinicreatingsolidcords (confusedwidr carcinoma) - Deformedandenlargedlobularunrts - Slightrisk ofcancer Fibroq'stic choges: cystically dilated duds, abundmt fibrosis, small dea of calcifi cation, sclerosing adenosis

"j

-v.-.i

.:,

JI

0

TUMORS Sfomaltumors €'N@ @

- Age: young women, peaks,iq3'd decade

- Mcroscooic: - Loosefibroblasticstroma sunoundsductlike or glandular spaceslined with cellshaving intact basementmembme. - Ductal spacesmay be open,round or oval (periductal fibroadenoma)or compressed into slit-like sFuctures (intraductalfi broadenoma).

. N.E.: l) Encapsulated, &eelymovable,1-10cm 2) Frequentlymultipleandbilateral,

l iiu.

(2) Phvllodestumor - Much less common drm fibroadenoma - Varies in size: few cm (4cm) to massive size distending the breast - Shows grossly leaflike clefts and slits (Gr. Phyllodes= leafJike) - Usually benign. some become malignant (low gade), tends to remain localized, may recur after removal, but only rarely m etastasizes

.. 1

Fibroadooma, comprcssed brut onnctive rissue (*) foming capsule, fibroblotic woma witlr elorgared @mpressed duds lined by nomal

:l

EBithelial tumors,

(3) Sacoma . Similar to malignantlesionsseen elsewherein the body e.g.liposarcoma. angiosarcoma, leiomyosarcoma. sarcomatous changein phyllodestumor ! Bulky tumor masr *i6

"ryg|gg. Angiosarcoma ofbreast:arises.either: a) spontaneousll,, b) ascomplicationofradiation treatrnentfor cancerbremt (riskup to 4%,5-10yearslater) b) in the skin ofchronically edematousarm aftermastectomy (Stewilt-Trevess)'ndrome)

t^

'l- 9.flg$S-ggl]u2gto*dr or smuses

within &e main lactiferousducts

- Mostlysolitary,lessthm lcm - Branchingpapillae,coveredu,ithcubicalepithelium -e!!dsal: unilut"ot *, - Spontaneous - Smallsubareolurnass

olfF

- Mostly benign

L lntmductal papillona: Iuge cystic dilared duct showing Iobulaled ductal tr€ll

FW6F -Epidemiolqg_andBiskJactors (l) I of8 womqr in USA develop cancer breast, l/4 will die as a result (nearly 45,000-50,000 deathsper )'ear)+*&b$*t@f {@ffi9s9) (2) dgg: increaseswi*r age, uncommon under 30- with steady increase till menopause,75oloare older &an age 50.

Intraductal papillma in main lactifercus duct Oeneath ueola),

(4) Geosraphic influences: higherin USA andNorthernEuropethan Africa andAsia (environmentalfactors)

(3) Genetic and famill predisoosition: - 5-10% ofbreast cancersare related to specific inherited gme mutation (tumor suppressorgetreon chromosome l7) - 5070 ofu'omen widr hereditary breast cancer (familial predisposition) have g€ne mutation

{F

Classification:

Q Eitherhaveinvadedthebasementmembranelmy4giyg infilnainel ot not (lglglnwivg cMcinoua in sitt/J.

h"

i9ht,bitateral in 4ot Wanthe Exogmous:

Post-menopausal: estrogenreplacementtherapy B Locations:

(6) Preexistingproliferativebreastdisease

on '.__J

(7) Cancerofcontrolateral breast(47oofpatients)

- Upperinner,lowerouter,lowerinnerquadrants: l0o./o each

(8) Ionizingradiation

&.rs\oQao.CQ\nUrO-* \dout\utQcr"t'0irufYlo-

ns

DISTRJBUTIONOF Tffi EISTOLoGIC T}?ESOF BREAST C{NCER TOTALCANCERS

tobulor 4ornocinl

h :, :. w:wc$qPsry,.!!q. i. :.:i-1i:,1 Lobularcarcinoma in situ

RWe$gg. q,.,,,,.,;::,::,. Lobularcarcinoma Mucinous(mucoid)crcinoma Medullarycarcinoma Tubularcarcinorna

PERCENT

!& ,.8e! 20

tre

..:t::.ilgs,

t0 2 2 6

NONINVASIVE (IN SITI) CARCINOMAS CONIFEDDY BASEMENTMEMBRANE,DO NOT INVADE INTO SIROMA

oRLyMpHovAscaARcHANNELs J!: ftI1bVC Lrtraductalcarcinoma(DCIS):

w1@-:*

mEI--' -Much more commonftan inralobular carcinomain situ

sff;e dx-Ylor;tt^t,

- Arise in 0reterminal ductlobular unit - Cells grow, fill andplug the ductsandductulesu"ith carcinoma cellsbut remainconfinedwithin thebament membrane -Variouspattems: a) comedocarcinoma b) noncomedocarcinoma c) mioopapillary d) Paget'sdisease

Yuttrrq{S *F (2) Noncomedocarcinom a: Monomorphictumor cellilllnl, with spacesthat areevenlydistribured md regxrlain shap@

| molitna.ytJ Qllcgapap4ary 4$c 4J4!4!c-stsFa t

trvX6t'artprtL

CJ 0Yr tliltfurrl Intraduct @inom4

nonmmedwinoma,

noplmic

cells surcud

holeswith sharpmrgins 6 ifpunchedout bv a cmkie cuuer

'g J

w

tobular. oarcinoma in situ (LCIS): - Monomorphiccellsin clustersin ductsandlobules - Neverform a mass(incidentalfinding),rarelyassociated with calcification aciniremainrecognizable - Do not distortthe tissues, - Birateratin20-40v") Oh\r/ tb-?DyO ,n f)ClS - Onethirdof womendevelofinvasiveLicinoini

*e%

YeA developtnva€i

bT a$r
Uaqcrnfi'rud

1*

Lobula cilcinom4 neoplasicpmlifemtionof cellsin reminal breretduas ad acini, small md round cells (30% risk for development of invcive reinoma)

IT OT)YW

s INVASIVE (INFILTRATING) CARCINOMAS

- Strmulatefibrosis that replacesbreast fat (mammo$aphic density)+ hrd palpable tumor mass (scirhous carcinoma) ' t'l&rY L4(tA - Extension ofthe growtlr may cause dimpling ofthe skin and retraction ofnipple. - Mcroscooic: scatterednests or cords ofmalignant cells in dense fibrous stroma - 2/3 expressestrogen or prcgestrone receptors I u'hite center(desmopl6ia) md periphenl yellowish d6

&r hrrncrps

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r*.**]lli;f,

ofnecrosis

degrro Ie {iUrarstreeur,

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DrclalCArnslt* Lu+onipCe :-a.::

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Paset's disease ofthebreast- 8tstn tg$i6n -Nipple lesiondueto breastcancer(l-2% ofcases)

tnh

- Skin is Aequently fissured, ulcerating and oozing. Superimposed bacterial infection is common. - Propnosis depmds on the mderlying carcinoma, i.e. not worsened by Paget's disease) - Microscooic: Invasion ofepidermis with neoplastic cells (paget's cells), scattered singly or clustered, sunounded with a clear halo

ides),associated u,ith IDC ) invasiveor

Drnl u,r/inrlrrido rn Dur}s tz) lnvasivelobularcarcinoma: - Makes 5-l 0% of all breast carcinoma - Rubbery in consistency, does not create a palpable mass. - Cells invade individually into stroma + sfiands oftumor cells, onecell u'idth (inthe form - Expresshormone receptors "fq)

- ;fureq"dy

rnr.tastiaSs

m%

x

-Tend to be large and fleshy, sheets of large maplastic cells, scanl sFoma Dresenthost reaction to the rl

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vr

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S*UlroiruuleteiOnal22

- Rre, lesscommonthanmedullarycrcinoma r Productionof[qucin intracellularlyandextracellularly intothe surrounding stroma+ softbulky gray-bluemasses >Express hormonereceptors

pAoiJ

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.*, r,r,rc.,n,{urrnr

crcinoma:

large flehy m6s, shets ud nesis of ells snouded

strom4little dmoplsia (benerprcgnosisthm IDC &

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b?o ntrAdrd4j ruburarcarcinoma, - Multifocal, in a single breast or bilateral - Rarely presents as palpable mass - Microscopic: well-formed tubules - Well differentiated, rare lymphatic spread, excellenl prognosis - ExDresshomone receDlors

I Colloid or mucinoustrcinma with abundmtbluidr mucinI

Mammoeraphy: - hcreaseddetection - Detectionof smallinvasivetumorsbeforebeingpalpable - Easily directedbiopsy - Signs: (l ) Density (2) Massdistortion (3) Calcification (4) Chmgeswith time

l$Features commonto all carcinomas;

6'ohsrtf lurn{

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anddeep ll&rylency to adhereto-pectoralis.muscle

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(4) During pregnaacy,tumorsspieadvffip-idly -+ exciteslocal inflmmatory reactionu.ithswelling,rednessmd tenderness (5) Spread: - Local - Llmphatic:nodalspreadis presentin 2/3 ofcasesat time of presentation - Blood:favoredlocations:lung,skeleton,liver, adrenals.brain

;

bl"nl cawsos puarld orarl<-T os A) tgngha-t

b4et?

fll Fantus{ t (Xstt' ^{*J ' Wl\ahb '1:

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Themajorprognosticcriteriaaccordingto the AmericanJoi9y' committeeon cancs: ,/ (l ) Sizeof primarytumor, ,/ (2) Lymphnodemelastases,/ (3) Presence ofdistantmetastases ,/ Stage0: DCIS andLCIS(5-years\riytfute:90o/.) StageI: Irvasivec arcinona:.2 gK lessin diameter.\9 nodes. No distantrnetast?,(5-year sun'ival rate:879t) Staee11A: - lnvasivecrlinomas 2 cm or lessin dimeter wifll involvg/axillarynodes.OR grealerthtr 2 cm but lessthan5 cm - lnvatile carcinorna i2Kze with negativJlpph nodes(5-yearsunival rate: n50a\

Staggll_B:- hvasivecarcinomas greaterthan2 crplrnsizebut less than 5 cm witb positive lymph noy'ds,On - Invasive carcinom a greater thaS$gin size with negative lymph nodes (5-y.5# survival rate: 75%)

StageIII A: - Invasivecarcinomy'of_aUsize with fixed lyrnph nodes,OR - lnvasive car,gilfomaof any sir with nonfixed llmph node StageIII B: Invasly6 carcinornawith skin involvement. chest wall or clinical inflammatory cmcinoma . or with asesto ipsilateral intemal mammmary llrnpfi nodes (5 year sun'ival rale 460/o\ : any cancer with distant metastasis:5-year suwival: I 3%

rreatment: QIAAWAU

Carcinoma:

(1) Surgery:mastectomy or lumpectomy (2) Radiation,post-operative (3) Cemothl'rapy

(4)Hormonar - -Iiunq(itn

MALEBREAST Glnecomastia:

(c6mpJcs ' ttC

(l ) Livercinhosis: inability of liverto metabolize estrogen (2)Estrogen-secreting tumors e.g.Sertoli cellcarcinoma (3)Estrogen therapy UCgd+eV ?ohp CA. - , (4)K.tmfettusyrdrome )6q/ -Trdf6 a^rcfirA O

(5) Physiologic gpecomastia at piberq'arid in extremEold age

- Rare, with a &equency ratio to breast cancer in female ofof I :125 - Becauseof dre scant mount of breast substancein males. the tumor rapidly infiltrates the skin and thoracic wall - zusk factors and patlrology ofmale breast cancer are r6markably to cance$ seen n women.

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Ic.q.srrl | -' -*- | A. -^ 70-year-old mm sawhis physicimfor a routbe health

TI.IEGASTROINTESTINAL TRACT

maintenanceexamination.On physicalexamination,therewereno rmrarkablefildings, but a stoolsanple waspositive for occult blood. A colonoscopywas perfonnedandshoweda 5-cm sessile massin $e upperportion ofthe descendingcolon at 50 cm from the analverge. The histologicappearance at low power of a biopsy specimenofthe lesionis shownin the figure below. The patient refusedfurther workup andtreatment.Five yearslater, he seeshis physicianbecauseofconstipation,microoltic anemia,and a 5-kg weight loss over the past6 months. On surgicalexploration,thtre ls a 7 cm massencirclingthedescending colon. Which ofthe followingreoplasmsis he_qow mostlikely to have?

lil-l a. (5, NOn-HoOgKrn lympnoma .:. (C) Villous adenoma + (D) Squmouscell cacinoma

ICACZ A 70-year-old manwith a lengthyhistoryofchronic alcoholismashadincreasing difficulty swallowingandhas noticeda 6-kgweightlossoverthepast2 months.On physical examination, tlere areno remarkable findings. Upper gastrointestinalendoscopyshowsa 3-cm ulcerativemassin the midesophagus tlat partiallyoccludesthe esophageal lumen. ilr= crcss [email protected]'r

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Iesionis shownbelow. Whichof thefollowingis mostlikely to be seenon microscopicsectionofthis mass? {. (A) Multinucleated cellswith intrmuclearinclusions

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't (C) Adenocarcinoma .i. (D) Thrombosedvascularchannels

IC A S E3 | For the pastyear,a 20-year-old mm hashad.increasingly voluminous,bulky,foul-smellingstoolsanda 1O-kgweightloss. Thereis no historyof hematemesis or melena.He hassome bloatingbut no abdominalpain. On physicalexamination, there areno palpableabdominalmassesandbowelsoundsarepresent. Which of the followinglaboratoryfindingsis mostlikely to be presenton examination ofhis stool?

A (B) Giardia lamblia cysts

-

* (C) Vibrio cholerae .i. (D) Entamoeba histolydca fophozoites

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IcASE;l

IC A S E5l

A 68-year-old womm has had substernal pain after meals for may years. For the past year, sbe has had increaseddifficulw swallou'ing both liquids and solids. On physical examination, there

il:il:T-T:5ffj":E*n'ffihr the foll_owing neoplasms?

A 53-year-oldwomanhashad nause4vomiting, and midepigasbicpail for 5 months. On physioalexamination,there areno significant findings. An upper gastointestinalradiogaphic seriesshowsgasb-icoutletobstruction. Upper sasbointestinal ;n ,i n i ,

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a n ,,i a - .- '- ^

- - ".t- .:- f

vvure! ur urc ruru*,rg oropr*ffiffia seen in a biopsy specimm ofthis mass? - * (A) Non-Hodgkin lymphoma .l. (B) Leiomyosarcoma

-ilpsiofthism

.1. (B) Leiomyosarcoma

t'. (C) Squamous cell cucinoma

.i. (C) Squamous cell carcinoma

r-

* (D) Non-Hodgkin lymphoma

reASEtl

I CA S E6l

* (A) Epi6elial dysplasia

A 44-year-oldwomanhashadinueasingdifficulry swallowingliquids md solidsfor the past6 months. On physical examinetr'on, her fingershavereducedmobility becauseoftaut, nondefonningskin. A bariumswallowshowsmarkeddilationof 'Jreesophagus widJn tbedista.lportion.rvherethereis mafl(edtunmal narrowrng.A biopsyspecimenflom drelower esophagusshowsprominentsubmucosalfibrosis with little inflammation.Whichof thefollowingis mostlikely to produce thesefindings?

{. (B) Helicobacterpylori infection

+ (A) Portalhwertension

't' (D) Adenocarcinoma

* (C) Barren esophagus

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arthritisofthe hipsandknees.Recmtly,he hashadepigasticpain with nauseaandvomiting'andan episodeof henaionisis. On' physicalexamination, thereareno remarkablefindings.A gastric biopsyspecimenis mostlikely to showwhich of thef;llow;g lesions?

A (B) Iron deficiency

-

* a

I CASE8 | A 35-year-old manhashad epigastricpainfor over I

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beginsa 2-week courseof antibiotics,but on day 4, he feelsbetter md discontinuestreatrent. Severalweekslater,the epigastricpain recurs. If the patientdoesnot seekfurther featnent, which of the followingcomplications is hemostlikely to develop?

{'-

A 2?-year-old manhassudden onsetofmarked abdominal pain. Onphysical examination, hisabdomen is

ffiemicroscooic appearance ofa sectionlhroughtheexcisedileum is shownin rbe next figure. Which ofthe following additionalcomplicationsis tle patientmost likely to develcpas a resultofthis disease orocess? .:. (A) Enterocutaneous fistula

.:.-

.:. (B) Fatmalabsorption\

a (C) Intussusception

.|. (C) Hepaticmetastases * (D) VitaminB, deficiency

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* (D) Hepaticabscess

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roI ICASE A 46-year-oldwomanwith a lengthyhistoryofheart_ bum and dyspepsiaexperiencessuddenonsetofabdominal pain. On physicalexamination,shehas severemidepigastic pain with glarding. Bowel soundsarereduced.An abdominatnlain filrn . radiographshowsfiee air underthe leff leafofthe diaphragrn.The patientis immediatelytakento surgery,and a perforatedduodenal ulceris repaired.Whichof the followioilir rnostlikely to haveproducedthesefindings? .:. (A) Campylobacter jejuni * (B) Cryptosporidimpanum {. (C) Entamoeba histolyica

ll I ICASE

A 59-year-old manhashadincreasing difficulty

swallowingduringthepast6 months. Thereareno significant findingson physicalexaminatjon.Uppergastrointestinal endoscopy showsareasoferythematous m-ucosa abov.thfl A biopsyspecimenfrom tbeloweresophagus hasthemicr6Glli appearance shoun in the nextfigure. As a consequence of this patient'scondition,whichofthe following complications is most likely to occur? {. (A) Hematemesis + (B) Squanouscell carcinoma

* *

(D) Lacerations (Mallory-Weiss slrndrome)

lrl IcASE A 49-year-old womaaseesherphysicialbecause

qself-iifriiffi*-md diarrhea,which haveoccurredseveraltimes during the past20 years. Eachepisodelastsabout2 weeksand resolves withouttreabent. Findingson physicalexamination ae unremarkable, but a stoolsampleis positivefor occultblood. LaboratoryshJdiesshowno ova or parasitesin the stool. Colonoscopyshowsdiffirseand uninterruptedmucosal inflammationandsuperficialulcerationextendingfrom the rectum to the ascendingcolon. Colonic biopsy specimensfiom the area show a difrrse, predominmtlymononuclea, infilfate in the laminapropria. Thepatientis at high risk of developing which of thefollou.ingcomplications?

-

+ (B) Diverticulitis {. (C) Primarybiliarycinhosis (D) Fatmalabsorption

*

(E) Pqirectal fistula formation

3

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|co'EA

A 4l-yer-old manhasbeenHIV positivefor $e past8 yearsandhasbeenreceivinghighly activeantiretroviraltherapy for the pastyear. For the past 2 weeks,he has experiencrdpain whm swallowing.He hashadno episodes of hematemesis and no nauseaor vomiting. Thereae no remarkablefindings on physicalexamination.Tlte CD4+ lymphocytecountis now 285/pl. Whichof 0refollowingconditionsis mostlikely to producethesefindings?

A 67-year-oldwomm hasexperiencedseverenausea vomiting,erJy satiety;anda 9-kgweightlossoverthe past4 months. On physicalexamination, sbehasmild musclewasting. Upper gastrointestinalendoscopyshowsthat the entiregastricmucosais

+ (A) Esophageal squmouscell carcinoma

* (A) Earlygasric carcinoma

* (B) Achalasia

{. (B) Chronic atrophicgastritis

{. (C) Loweresophageal fibrosiswith stenosis

t (C) Granulomatous inflammation

croiefi

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nac

rn

erunrn,r^r'.

1E

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gastomlestinalradiographsshowthat the stomachis small and shrmken. Which of the following is most likely to be found on histologicexaminationofa gastricbiopsyspecimen?

ltnths

VlaSheat

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151 ICASE A 5l-year-old manhassudden onsetofmassive

ilffi*i,lH:i.;*Ti:

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blood pressure85/50mm Hg. Laboratorystudiesshow a atocrit of 2 I o/0.The serologictest resultfor HBs Ag is positive.He hashadno prior episodes ofhematemesis. The hematemesis is mostlikely to be a consequence ofwhich ofthe followine? .!. (B) Barrett esophagus

-r. (C) Candidaalbicansinfection * (D) Squamous cell carcinoma

16l IEASE

I CASE17I

parn fbr I

swallowsfood. Physicalexaminationshowi no abnonnalfindings. Uppelgashointestinal endoscopy shows0.5to 0.8-ommucosalulcersin theregionofthp middleto lower . esoplragus. The shallowulcersareround,sharplydemarcated, and havean erythematousbase. Which of tlre follou.ing is mostlikely to producethesefindings?

An I I -month-oldpreviouslyhealdrinfant hasnot produceda stool for I day. The mothernoticesthat the infanfs abdomenis distended.On physicalexamination,the infant,s abdomenis very tenderandbowel soundsarenearlyabsent.An abdominalplain filrn radiographshowsno free air, but thereare distendedloopsof smallbowel with air-fluid levels. Which of the followingis mostlikely to prodpcethesefindings? '!. (A) Meckeldiverticulum

+ (B) Gastroesophageal reflux disease * (C) Candidaesophagitis

* (B) Hirschsprung disease .!. (C) Pyloric stenosis

+ (D) Mallory-Weisssyndrome

-

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FASErsI A 22-year-oldwomanhashad severalepisodesof aspirationof food associatedwith difficulty swallowingduring the auscultation,cracklesareheardat the baseofthe barium swallowshowsmarkedesophageal dilation ofthe loweresophageal sphincter.A biopsy specimenfrom the lower esophagusshowsan absenceofthe myentsricganglia. Which of tbe following is the mostlikely diagnosis?

I CASEle I A 20-year-oldwomanin her ninth month ofpregnancyhas rncreasingpain on defecationandnoticesbright red blood on the toilet paper. Shehashadno previousgashointestinalproblems. After shegives birrh, the rectalpain subsides,andthere.isno more bleeding.Which ofthe follou'ingis themostlikely causeofthese findings?

t (A) Hiatalhernia

* (A) Colorectalcmcer

* (B; Plmmu-Vinsonsyndrome

t'. (B) Ischemiccolitis

* (C) Barett esophagus

* (C) Intussusception

.l (D) Systemic sclerosis

tt'(E) Volwlus

-

CASE20

CASE2I

A 24-year-oldwoman gives birtl to an infant at term after an unconplicatedpregnancy. The infant's lengthandweight areat the55epercentile.Thse is no significantpassage of ;riiEe davsaitrbrnn' rirenrmt vom*s ariorai fll leedrngs.Un physlcalexamlnation, $e infantis afebrile,but the abdomenis distendedandtcnderandbowels soundsarereduced. An abdominalultasound scanshowsmaked colonic dilation above narrowsepent in the sigmoidregion. A biopsyspecimen from the narrowedregion showsan absenceofganglion cells in the muscle wall andsubmucosa. Whichof tbe followingis mostlikely to producethesefindings? *-

(B)Trisomy2l

* (C) Volwlus

(D) Colonicatresia

* (A) Adenocarcinoma (B) Non-Hodgkinlymphoma {' (C) Tubularadenoma r-

.!. (E) Intussusception

ICASE 22 | A 27-year-old manhashadintermittentcrmping abdominalpain andlow-volumediarrheafor severalweeks. On physicalexamination, he is afebrile;thereis mild lowerabdominal tendemess but no masses, md bowelsouds areDresent.A stool sampleis positivefor occultblood. The symptomssubsidewithin I week. Six monthslater,the abdominalpain recus with perimal pain. On physicalexamination,thereis now a perhectalfistula. Colonoscopy showsmanyareasofmucosaledemaandulceration and someareastlat apper normal. Microscopicexaminationof a biopsyspecimenfrom an ulceratedareashowsa patchyacuteand chronic infl ammatory infi ltrate, cr)?t abscesses,an{sevqral-_

Iryglrc.

A 38-year-old manwho hasbeenHIV nositivefor I 0 yearshashad severenauseaandvomiting for the past2 weeks, On physicalexamination,he is afebrile. A stool samile is positivefor occultblood. The abdornenis not distended,theri areno palpable massesor orgaromegaly,andbowel soundsarepresent.The patienthas oral thrush. Thereare severalreddisb-purple,0.5- to 1 cm noduleson the skin ofthe trmk. Laboratorystudiesshow a CD4+lymphoc)4ecout of I I 8/pL. Uppergashointestinal ardoscopyshowsI 2 reddish-purple, 0.6 to I .8 crn,gastricmucosal nodules.A biopsyspecimen ofthe nodulesis mostlikelv to show whicbof the followingneoplasms?

which;f rhefouo*ing*:ildlffi

explainsdresefi ndings?

(E)Squamouscellcrcinoma

E sErIA 49-yetr-old man has complained

..heartbum', of affer meals for the past decade, There are no remarkable findinss on physical examination. Upper gastrointestinal endoscopy.ii.

themucosashou's Whichof the following t (A) Esophageal varices + (B) Radiation6erapy {. (C) Achalasia

(B) Amebas t (C) Shigellosis

(D) Sarcoidosis

+ (E) Iron deficiencymemia

.1.(E) Ulcerativecolitis

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n) D

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20\ A

?\D

AA B) D

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A 65-year-oldwomm goesto her physisianfor a routinehealli maintenanceexamination. A stool sampleis

lffifi"Sii#frffi

most likely to developin this patient? * (A) Adenocarcinoma

:1

'-

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A (C) Bowelobstilction A (D) Malabsorption .!. (E) Toxicmegacolon

.:a:4

ree A 45-year-oldwomanhashad increasingabdominat distentionfor the past6 weeks. On physicalexamii.t"",-O"* i. al abdominalfluid wave andbowel soundsarepresent. Paracentesis yields1000mL ofslightly Uouayserous hula. Cytologic examinationof the fluid showsrr"tign-t consistentnith adenocarcinomalhe patient,Jmedical ""ii,hisory indicatestlat shebashadno majormedicalillnesses andno surgrcatprocedures.Whichoftle followingconditions is most likely to havepreceded the development ofthe adenocarciloma? ta (A) Ulcerativecolitis (B) Crohndisease f. (C) Diverticulosis

(D) Coloncucinoma

* (E) Hirschsprung disease

=

ICASE,;I A 32-year-old man seesthephysicianbecause hehas experien_ced nauseaandvomiting for tbe iasi week. On physical exmttrauon,he appears cachecticandsaysthathehasnoticeda I 5-kg weight loss overthe past2 months. A I 0_cmnontender massis palpablein themidabdominalregion. Aa abdominal CT scanshowsthat the mass

*(A) Bluutingatrdflatteningofvilli eontainingincreased numbersoflymphocytesandplasmacells .1.(B)Denselypackedtubularglands linedby dysplastic cellswith n)perchromahc nuclei

* (D) Irregularulcerationwith chronic inflammation and Eanulomaformation

l*sEA man

overthepast24 hours. On pbysicalexamination. there is difrrse abdoninal tendemess.n e i. tyrnpaofi--'"Utiorr"n widrout a fluid wave,andbowel sounds areneady abselt. Tiere is well-healed,S-crntansversescarin the rigtrt lower quadrani of * theabdmen. Thereisnocapurmedusae.,{stool ;ilL' negativefor occult blood. An abdominalplain filrn radiopranh showsdilatedloopsof smallbowelwith air-fluiaf"uelr, U-uitlo" the sugeonnotices,a 20-"r p;;; lparotomr, 1t i::::li f or reqdrsb:btackilew that changesabruptlyto pink_aDDetrins on bothdistalandproximalmargins.Tte patieni,smeiical ::wet .-;historvis simifienr nntvfn "of the followingis mostlikely ro iave producidtbeffirfinrs? -1g_!,j;;

€. (A) Adenocarcinoma ofthe ileum

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.i. (C) Croh disease t!'(D) Vohulus * (E) Intussusception

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