ORAL CAVITY 1. Anatomy a. Lined by squamous mucosa (stratified, non-keratinized), submucosa contains islands of minor salivary glands b.

Reactive changes: increased roliferation !y er lasia " e#cessive surface keritinization $. %isorders (stuff %r. & said to kno' is in bold, at!ology lecture integrated into c!art) (A)*+L+,120/,0 %ental caries (eriodontitis +ral tori Amalgam tattoo 3ordyce s ots 2 ulis fissuratum (a illomatosis (a illoma (very common) (a illary roliferation of benign squamous lining " !y erkeratosis " koilocytes *ig!ly vascular lesion 'it! granulation tissue, eventually fibrous .L/0/.AL Localized, rogressive destruction, starts at e#ternal surface dissolution of inorganic com onents by bacteria acids /nflammation of gingiva, resor tion of alveolar bone, degen of eriodontal ligament Area of !y erostosis, very common /ncor oration of insoluble silver amalgam by nearby tissue !istiocytes igmentation /m ortance is to differentiate from malignant melanoma 2cto ic sebaceous glands 3ibrous inflammatory !y er lasia, usually due to ill-fitting dentures 0umerous a illary ro4ections, usually due to ill-fitting dentures Lesion !as 5ras berry6 a earance 1enign tumor, 7caused by irritation, infection, virus (*(8) Lesion looks like tree s routing u from oral mucosa, very granular /rritation fibroma 9 a illoma t!at !as 5'orn do'n6 .ircumscribed collection of us (eria ical (e#t of caries), gingival, and eriodontal ty es &igrating ovoid inflammatory lesions on dorsum of tongue .om letely benign 8ery ainful su erficial ulcers t!at ersist for ;1' +ccur on non-keratinized mucosa Assoc 'it! tender lym !adeno at!y Look in !istory 5bit my tongue $ days ago6 )rauma secondary infection, '!ic! !eals in ;1<d .an mimic carcinoma, '= slo' !ealing lesions in ts '= oor !#, do a bio sy 2nvelo ed ds%0A virus '= ca sid, 1A<nm in diameter 9 !er es virus (rimary infection: vesicular eru tive lesions on mucus membranes Latent in trigeminal ganglion Becurrent infection: usually vermillon border, triggered by stress=immunoC Assoc w/ immuno (autoimmune, */8, diabetes, c!emo) D look for underlying causeE Most common o!!ortunistic in"#n in $IV !ts% o"ten "irst mani"estation &ra'/cream' !la(ues that CA) *e scra!ed o""% revealing er'thematous *ase ,eneralized disease of collagen )ongue becomes stiff=boardlike " microstomia affects eating, s eaking, s'allo'ing 2#treme 'idening of eriodontal ligament on #ray .!elosis, glossitis, beefy red tongue, fissuring tongue 8it11$ defcFy t# '= /0G2.)2% 11$ Hnusual igmentation due to stimulation of ituitary melanocytic activity &ingivitis% gingival h'!er!lasia% !etechia% ulceration% cervical l'm!hadeno!ath' (us!ing on inflamed tissue 'ill e#!ibit blood 8iral infection of o.l bony enlargement of 4a' " flaring of teet! 2ru tion of symmetrically distributed A(s D ruritic, lanar, ur le, olygonal a ules Beticular form (aka Iick!amFs :triae) is classic resentation, sym tomatic > c!ronic I!ite lacy streaks and small a ules :taining on teet! %onFt use bt' $nd trimester D Jy, 'ill !ermanentl' stain teeth *luish color 2nlargement, !y ersensitivity ,ingival !y er lasia Autoimmune dz 'it! vesicles and bullae, "0ikolskyFs sign THICK white !la(ue on side o" tongue that CA))OT *e scra!ed o"" O"ten "irst sign o" $IV in"ection Ma' also !resent with .ar!osi/s sarcoma (most common cancer in $IV !ts) :ingle or multi le flat bro'n-red lesions on oral mucosa (ain=bleeding are common Along 'it! !airy lueko lakia, is often t!e first resentation of A/%: Acetone breat!, increased caries MlinkB !y o=an!idrotic skin " artial=total anodontia, malformation of teet! Also affects sebaceous glands, nails, !air +ral lesions less common, variable resentation (usually tongue ulcer) :elf-limiting acute bacterial inf#n of kids by 1artonella (lives under cla's) 1ones, stones, groans, syc!ic moans 2nlarged tongue, li s 2ntire dermatome (doesnFt cross midline of tongue) is involved :udden enlargement of mandible, flaring of teet!, macroglossia as adult

Abscess ,eogra !ic tongue A !t!ous ulcer (canker sore) )raumatic ulcer (most common) *er es virus (*:81 > $, 218, .&8, 8?8, **@) Moniliasis/thrush (candidiasis) :-:)2&/. :cleroderma

:!allo' ulcers covered by fibro urulent e#udates

1allooning degeneration of e it!elial cells '= viral inclusions, multinuclear cells -east '= seudo!y !ae

8it 1 malnutrition Addisons Leu+emia (A&L, .LL, .&L) (agets Lic!en lanus

2#cess keratin " dense lym !ocytic infiltrate '=in lamina ro ria

3luorosis Tetrac'cline 2ryt!romycin %ilantin (em !igus $air' Leu+o!la+ia (,-V% not $IV) Ka osiFs :arcomaLLL

)!ickened mucosal lining 'it! arakeratosis &alignant vascular tumor '= small blood vessels, s indle cells, cytologic aty ia

%iabetes 2ctodermal dys lasia )uberculosis .at scratc! dz *y erarat!ryroidism *er es zoster Acromegaly

N.

O.

:alivary glands a. (arotid D all serous, sublingual D all mucinous b. 01ogren/s s'ndrome autoimmune destruction of e#ocrine glands #erostomia, dry eyes i. (at!ology s!o's c!ronic inflamm " fibrosis .ancer a. )ransformation is continuum, normal !y er lasia dys lasia ./: invasive carcinoma i. .ou led 'it! rogressive genetic abnormalities b. :tage=grade gives # D greater de t! of invasion, involvement of nodes, mets all 'orsen c. .arcinomas P@Q, sarcomas OQ d. 0(uamous cell carcinoma 234 o" all oral cancers i. Ris+ "actors: smoking " 2t+* synergistic ii. Tongue most common, !ard alate least common site iii. 0#: ain, bleeding, non-!ealing sore, lum =mass, '!ite=red atc!, difficulty eating=s'allo'ing=talking, numbness iv. 5atholog': e# ansion of basal cells, loss of maturity '= !ig! 0:. cells at e it!elial surface v. 8ariants: verrucous (locally destructive, rarely met, 'arty), lym !oe it!elioma (assov '= 218), s indle cell (aggressive) e. :alivary gland tumors i. (arotid: !ig!est incidence, lo'est malignant otential ii. :ublingual: lo'est incidence, !ig!est malignant otential iii. &a4ority are benign, if malignant, ma4ority are mucoe idermoid 1. A<Q of &/0+B salivary gland tumors are malignant (A)*+L+,.L/0/.AL 6hite !la(ue/!la(ue on mucus mem*rane that CA))OT *e removed *' scra!ing LO6 !otential "or malignant trans"ormation &ost are benign, 1H) if t!ey ersist t!en bio sy Red !atch/!la(ue (non7*lanching) that CA))OT *e removed *' scra!ing $I&$ !otential "or malignanc' (879# more than leu+o)% alwa's *io!s' /f s eckled lesion (red > '!ite), still bio sy because of t!e red (recedes li cancer, due to c!ronic outdoor e# osure (sun) or i e smoking 1enign roliferation of endot!elial cells, often regresses s ontaneously 8ery large locally destructive igmented gro't!, rare :ee above &ost common salivary tumor .ommonly resents in arotid &ost common malignant tumor &ost common malignant tumor of minor salivary gland /nvolves nerves, t!us difficult to resect

(B2-.A0.2B+H: Leu+o!la+ia

)!ick layer of surface keratin *ig! grade intrae it!elial dys lasia

,r'thro!la+ia (:/0) :olar .!eilosis 02+(LA:&: *emangioma &alignant melanoma Invasive 0CC (leomor !ic adenoma &ucoe idermoid carcinoma Adenoid cyst carcinoma

:ee above Iell circumscribed mass, benign roliferation :quamous and glandular mor !ology :'iss-c!eese mor !ology

)o : candidiasis, yeast '= seudo!y !ae, tetracycline staining, gingival !y er lasia in A&L, !airy leuko lakia 1ottom: !omogenous leuko lakia, s eckled eryt!roleuko lakia, oral :.., normal vs dys lastic oral squamous e it!elium LIV,R 1. Anatomy a. 1lood su ly i. *e atic artery: $AQ of flo', +$ ric! ii. 5ortal vein: RAQ of flo', +$ oor but nutrient ric! 1. 3ormed via :&8 and s lenic vein $. L+I ressure system N. 1lood drains into sinusoids, '!ic! drain into !e atic v iii. .ollateral circulation 1. 2so !ageal veins drain into ortal v, t!us ortal *)0 eso !ageal varices 2. Bemnant umbilical vein drains into ortal v, t!us ortal *)0 s ider angiomas 3. *emorr!oidal le#us drains into ortal v, t!us ortal *)0 !emorr!oids iv. *e atic vein: formed by central v sublobular v B=L !e atic v /8. 1. central vein found at center of 5classic6 lobule

b.

c.

d.

$.

N.

O.

3unction a. %eto#ification b. ,lucose !omeostasis (,0,, glycogenolysis) c. .!olesterol=), metabolism d. (rotein metabolism (i.e. urea cycle, ammonia urea) e. (rotein synt!esis i. AA (req A:), AL), t!us cell deat! release of t!ese enzymes and !ig! serum levels) ii. Albumin iii. (rocoagulants (all e#ce t 8///) " vit K-mediated modification of 3//, 8//, /M, M iv. Anti-coagulants ( rotein ., :, anti-)*1N, lasminogen) f. 1ile acid roduction from c!olesterol i. .on4ugated '= glycine=taurine, e#creted into canaliculus intestine for fat absor tion, P<Q reabsorbed in ileum g. 1ilirubin metabolism i. *eme breakdo'n bilirubin con4ugated to glucoronic acid by !e atocytes e#creted into canaliculus intestine for e#cretion, some decon4ugated by bacteria, 1<Q reabsorbed in ileum 1asic a roac! to d# a. *>(: often as#, non-s ecific s# (fatigue, anore#ia, 0=8=%, fever), s ecific s# (4aundice, dark urine, lig!t-colored stools) b. Lab tests i. 2levated aminotransferases: hallmar+ o" he!atocellular in1ur' , due to leakage of enzymes u on cell lysis 1. Largest increases are seen '= acute !e atitis ii. 2levated alkaline !os !atase: hallmar+ o" cholestasis, due to over roduction by !e atocytes iii. 2levated bilirubin: seen severe in4ury (aminotransferases are raised first) 1. +nly uncon4ugated bilirubin is measured (uncon4ugated in serum, con4ugated is e#creted) $. %d# '= increased bilirubin: a. /ntravascular !emolysis increase unconjugated bilirubin b. Liver d: or *iliar' tract damage conjugated *iliru*in in the serum i. %es ite necrosis, remaining cells !ave ca acity to con4ugate, but not to e#crete into bile ducts iv. Lo' albumin: seen only in cirr!osis, '!en liver !as lost significant ability to synt!esize v. (rolonged (): seen in any liver dz, es cirr!osis, due to decreased synt!esis of clotting factors %isorders

2. R heart "ailure he!atic congestion, seen on *>2 around central v :inusoidal system: blood vessel mes! com osed of discontinuous endot!elium 1. *e atocytes are bat!ed in blood derived from ,/ and ancreas $. .ells of t!e sinusoidal mes! are arranged in 5cords6 of single-layer cells 5ortal triads: ortal veins " !e atic arterioles " bile ducts, !eld toget!er by .) i. 1ile flo' and blood flo' is o osite in direction (bidirectional) 1. 1ile roduced by !e atocytes, travels via caniliculi to intra!e atic ducts B=L !e atic ducts common !e atic duct gall bladder for storage 2. After meal, bile released from ,1 cystic duct common bile duct ('!ere ancreatic duct 4oins) duodenum via am ulla of 8ater .ell ty es i. *e atocyte: 5stable6 cell, t!us infrequent re lication but ca able of regeneration ii. Ku ffer cells: liver !agocytes, also store !emosiderin iii. :tellate (/to) cells: undifferentiated, im ortant role in differentiation to fibroblasts '= fibrosis iv. 2ndot!elial cells: fenestrated Lobules i. .lassic lobule: !e#agonal '= central v at center, used for describing endocrine function ii. (ortal lobule: triangular, used for describing bile role iii. Acinus: diamond s!a ed '= ortal traid at center, used for defining erfusion=disease 1. ?one 1 surrounds ortal triad, cells are !ig!ly erfused t!us resistant to isc!emia $. ?one N surrounds central vein, cells are most vulnerable to isc!emic in4ury v.

3our main clinical ictures from numerous etiologies, some of '!ic! can lead to any=all of t!e clinical syndromes $e!atitis Active deat! of !e atocytes (!e atocellular in4ury), usually due to to#ins, inf#n, or isc!emia A.H)2 +ccurs days - 'eeks Iides read !e atocell in4ury, '!ic! is balanced by regenerative c!anges Viral in"#n (most common) )o#ins /sc!emia Autoimmune Iilsons disease Lobular neutro !ilic infiltrate (2t+*, autoimmune 9 77777) :'elling, lo*ular disarra', acido !il bodies (indicate a o tosis), colla se of frame'ork *ridging necrosis 0+ fibrosis 8ery !ig! AL)=A:) Alk(, bili, ro)*1 can be 'nl 3HL&/0A0) +ccurs ra idly, failure '=in @' :udden, massive necrosis (SA<Q) leading to acute !e atic failure, '=o regeneration Viral in"#n (!e A-2) Acetomino!hen (oisons Little in"lamm since so sudden (rominent lobular colla se 0hrun+en liver '= 'rinkled ca sule 0+ fibrosis .*B+0/. +ngoing for S@m, cirr!osis if not t#Fed 3ocal necrosis of ortal triads '= inflamm s illover iecemeal necrosis VIRAL in"#n (!e 1-%) Autoimmune a-1 antitry sin Iilsons disease (ortal lym !ocytic infiltrate (autoimmune 9 !lasma cells) ;i*rosis '= ortal- ortal bridging

%efinition

2tiology

*istology

%#

Bidiculously !ig! AL)=A:) Alk(, bili elevated (ro)*1 'nl

:lig!tly !ig! AL)=A:) Alk(, bili, ro)*1 'nl

:# Bange: fatigue, fever, 0=8, abdominal ain, 4aundice, dark urine, lig!t stools (# Hsually reversible if self-limiting &ay require liver trans lant Autoimmune !e atitis may resent as acute, fulminant, or most commonl'% chronic &ore common in 3, more aggressive in younger ts, !alf 'ill !ave anot!er autoimmune dz :#: rofound fatigue, nausea=anore#ia, u er abd ain %#: A0A", A0.A", increased AL)=A:), alk( 'nl )#: steroids

)ends to be as#, firm liver on al Anti-virals necessary if t!atFs t!e cause

Viral !e atitis may resent as acute, fulminant, or c!ronic, de ending on virus 1io sy only indicated if !er es virus is sus ected Hncommon viruses .&8: mild !e atitis in c!ildren, let!al in immunosu ressed 218: common if mono, self-limiting *:8: seen in immunosu ressed, !ig! mortality, viral inclusions on L&, t# '= acyclovir, vidarabine Common viruses )BA0:&/::/+0 3ecal-oral :)BH.)HB2 ssB0A LA1: $AV IgM A* (active) $AV Ig& A* ( rior) .L/0/.AL Barely acute failure /cterus=mortality more common in adults t!an eds 5rolonged cholestasis 1aundice )o carrier or chronic state (i.e. al'ays resolves) Barely acute failure Gaundice in $AQ Bisk of carrier state: neonate P<Q, adult AQ $=N of carriers c!ronic 9 increased ris+ o" $CC /f e# osed, bot! vaccine and *1/g are given Most common cause o" chronic viral he!atitis &ost common cause of liver trans lant 8ery mild, often subclinical (if s# 9 cirr!osis) .oinfection (acute 1 " %) often resolves 0u!erin"ection (acute % " c!ronic 1) cirr!osis in A-1<y, bad #E )o carrier or chronic state 3atalities only in regnant 'omen )# Vaccine :u ortive

*e A

*e 1

1lood (/8%H) :e# (:)%) 8ertical

/ncom lete ds<)A

:ee belo' IgM anti7$-c (.B of *18 %0A

*e .

*e %

*e 2

-lood (IV<=) :e# (:)%) 8ertical 1lood (/8%H) :e# (:)%) 8ertical 3ecal-oral

B0A

(.B of *.8 B0A (genoty e im t #)

B0A virus '= *18 coat (*1sA,) B0A (.B of *28 B0A

Vaccine Acute t# is su ortive .!ronic t# is inter"eron% teno"ivir Inter"eron >Ri*avirin :)A)-. )# !e 1

:u

ortive

Acute failure $-V is most common agent causing acute liver failure, very rare but !as !ig! mortality :us ect if increased (), decreased liver size, ence !alo at!y=!y oglycemia $e! - antigens *1eAg " serum *18 %0A: indicates viral re lication=active inf#n, order IgM anti7$-cAg *1sAg: often used to screen for inf#n since first Ag to a ear a. (") +0L- in active inf#n D if recovered=vaccinated, you 'ill not see t!is b. Iindo' as Ag is cleared and Ab are synt! in '!ic! an infected erson 'ill be (-) c. )!us, al'ays order /g& anti-*1cEE *1cAg: core Ag is only seen if infected=recovered, not if vaccinated /g& anti-*1c: resent during active inf#n, covers t!e 5'indo'6 /g, anti-*1s: resent if recovered or vaccinated

LB: acute viral !e atitis, iecemeal necrosis of !e A, ortal bridging in c!ronic !e atitis Cholestasis 3ailure of bile secretion bile retention in !e atocytes (to#ic necrosis=fibrosis=cirr!osis) and !y erbilirubinemia (con4ugated) a. b. c. d. e. f. /ntra!e atic causes: to#ins, se sis, (:., (1. i. .analiculi are invaginations of !e atocyte a ical membranes '= attac!ed alk( ii. /f any dysf#n in membrane c!olestasis " markedly !ig! alk( 2#tra!e atic causes: obstruction via calculi, stricture, tumor, (:. (at!ology: !e ato accum of bile=bile lugs (trans ort dysf#n), ductal rolif, foamy degen (accum of li ids), bile infarct (e#tra only) :#: cutaneous D 4aundice (e#cess bile)=#ant!omas (e#cess c!ol)= ruritis (bile acids itc!), fat malabsor tion, osteo orosis (8it% defcFy), coagulo at!y (8it K defcFy), acholic stools %#: ver' high al+5 (!ig!est in (1.) due to over roduction, not leakage " confirmatory AF nucleosidase (s ecific for liver), ronlonged (), imaging (r=o obstruction), A&A" in (1. )#: surgery if obstruction, cholest'ramine, arenteral 8itK, medium chain trigl'cerides, trans lant if (:.=(1.

LB: #ant!elasma, #ant!oma, 4aundice, bile accum due to c!olestasis Cirrhosis :lo'ly rogressive disru tion of normal !e atic arc!itecture by combination of cell deat!, fibrosis, and regenerative nodules a. b. c. +ften caused by c!ronic !e atitis=c!olestasis due to ,tO$ (most common), viral inf#n, biliary dz, !emac!romatosis +ften rogresses to c!ronic failure :tellate cell transforms into myo-fb increased collagen fibrotic nodules '!ic! colla se normal reticulin frame'ork i. /ncreased resistance to blood flo' ortal *)0 (see belo') ii. /m aired diffusion of metabolites iii. /m aired flo' of bile Com!lications: increased risk *.., ascites eritonitis, variceal ru ture s!ock, congestive s lenomegaly !y ers lenism (at!ology i. ,ross: firm, rubbery, nodular liver '= cobblestone a earance ii. &icro: nodules surrounded by fibrosis, Mallor' h'aline=fatty c!anges if due to 2t+* :#: range from as# !e atocellular dysf#n (bleeding, fatigue, 4aundice, muscle 'asting, !y ogonadism) ortal *)0 %#: firm=nodular liver, ascites=ca ut medusae, !y oalbumin, !# of liver dz

d. e.

f. g.

LB: macronodular cirr!osis, regenerative nodules '= rim fibrosis, &allory !aline (brig!t ink), alco!olicEE ;ailure 2nd stage liver, in '!ic! trans lant is t!e only cure Loss of SP<Q !e atocellular function Acute i. 1est e#am le is fulminant !e atitis ii. .onfluent necrosis ence !alo at!y=coagulo at!y '=in $mo of s# onset '=o re-e#isting liver disease iii. :#: 1aundice% mental status changes (seizures, asteri#is, !y errele#ia), shrun+en liver, !y oglycemia iv. Labs: AL)=A:) initially !ig!, t!en dro off as necrosis is com lete, !y erammonia (failing liver cannot deto#ify it), !y erbilirubinemia, !y oglycemia (no ,0,), rolonged () (no clotting factor synt!), 22, abnormal=cerebral edema v. )#: trans lant, su ortive '!ile 'ait - e.g. control glucose, revent inf#n=bleeding, t# cerebral edema c. .!ronic i. 1est e#am le is severe cirr!osis ii. Assoc '= ortal *)0 and all its manifestations iii. :eizures uncommon, liver 'ould be firm=nodular rat!er t!an s!runken (ortal *)0 a. %ue to increased resistance (mec!anical obstruction, i.e. e#cess collagen, increased 8.), increased flo' (anastomoses, 8%) b. .auses i. (re-!e atic (e#) ortal v t!rombosis ii. /ntra!e atic (e#) alco!olic cirr!osis iii. (ost-!e atic (e#) !e atic v t!rombosis (1udd-.!iari), B !eart failure c. &anifestations iv. : lenomegaly 1. .ongestion slo' mvmt of cells t!ru s leen increased destruction aka 5!y ers lenism6 2. Labs s!o' t!rombocyto enia, leuko enia, !emolysis increased *iliru*in v. 8arices 1. 1acku into umbilical v remant ca ut medusae 2. 1acku into coronary v (aka L gastric v) eso !ageal varices a. &ost clinically significant since ru ture !as !ig! mortality N. )#: decrease ortal 1( via somatostatin analogue (octreotide) , )/(: (surgical s!unt '!ic! decom resses) vi. Ascites 1. .ell deat! decreased s'nth o" al*umin decreased oncotic ( " ortal *)0 free fluid in abdomen 2. Liver also releases 0+ 8% decreased effective lasma vol kidney activation BA:=A%* 0a=*$< retention N. %d# includes malignancy, !eart failure, )1, t!us analyze ascitic fluid a. /f (serum albumin) D (ascites albumin) S 1.1 9 ortal *)0 b. /f malignant cells in fluid 9 cancer c. /f I1.s, "culture 9 inf#n O. .om lications include eritonitis, umbilical !ernia, leural ascites A. )#: 0a=*$< restriction, diuretics, aracentesis vii. (ortosystemic ence !alo at!y 1. Acute: seen in acute=fulminant !e atits, mental status c!anges '!ic! rogress to coma $. .!ronic: seen in cirr!osis=c!ronic failure, reversible if reci itating factors t#Fed a. 3actors: e#cess rotein intake, ,/ bleed, !y o)0, inf#n b. :#: mental status c!anges, !y errefle#ia, asteri#is c. 7due to !y erammonia and ,/ flora infiltration N. )#: fi# reci itating factors, lactulose (dra's out ammonia) viii. *e ato-renal syndrome 1. Benal failure due to advanced liver disease a. b.

A.

@.

R.

$. :evere oliguria but normal tubular f#n (i.e. 0+) due to A)0) N. &ust rule out re-renal azotemia '= volume e# ansion trial (s# 'onFt resolve if itFs a liver roblem) O. )#: trans lant %rug induced !e atoto#icity a. +ver @<< im licated drugs, leading cause of AL3 b. <iagnosis o" e#clusion, t!us !ig! sus icion '= any une# lained liver dz c. B3: elderly, female, obese, underlying liver or systemic dz, oly !armacy, 2t+* d. 2#am le resentations i. Acute !e atitis - !enytoin ii. .!ronic !e atitis - a-met!ydo a iii. .!olestasis - estrogens iv. &i#ed !e atitis=c!olestasis D c!lor romazine v. &acro fatty liver D corticosteroids vi. &icro fatty liver D tetracycline +% vii. .irr!osis - &)M viii. ,ranulomatous - allo urinol i#. 0eo lastic - vinyl c!loride e. (redictable, i.e. anyone taking it 'ill get some dose-related to#icity 'it! kno'n !istologic c!anges i. Acetamino!hen centrilo*ular (:one ?) he!atocellular necrosis ( ic) 1. +% .-( OA< induction over roduction of to#ic metabolites over'!elmed con4ugation " de letion of glut!at!ione $. Antidote is n-acetylcysteine, '!ic! increases glutat!ione stores f. Hn redictable, i.e. idio at!ic (ma4ority of reactions) i. )!eory T1: drug metabolite " carrier rotein 9 ne' Ag immune res onse (!y ersensitivity) and !e atoto# 1. %elayed onset " common 5allergic6 resentation (ras!, eosino !ilia) su ort ii. )!eory T$: drug " genetic abnormality unusual to#ic metabolite=!ig! levels !e atoto# g. )#: most resolve '!en d=c drug, more serious may req su ortive care or trans lant .ancer /ncidence &ost common rimary malignancy :trong assoc '= *e 1,., cirr!osis, and aflato#ins (as ergillis) 3ibrolamellar in younger, no assoc '= above dz, better # &ost common tumor (PAQ) .linical &alaise, 'eig!t loss, fatigue Abdominal ain=fullness Liver failure (ulmonary mets %# marker: elevated a7"eto!rotein (oor # (oor # (caug!t late) (at!ology )ons of cords of tumor cells +ften !roduce *ile Assoc '= cirr!osis, b-vessel invasion 3ibrolamellar: 'ell-diff, unifocal, abundant collagen &ultifocal involvement Adenocarcinoma of intra-! bile ducts )O *ile !roduction Intense desmo!lasia 8ascular rolif, tons of endot!elium Hnifocal nodule of benign !e atocyte '= central scar radiating out'ard %iffuse nodules but no fibrosis (0+) cirr!osis) 1enign roliferating !e atocytes

*.. )y ical 3ibrolamellar &etastasis .!olangiocarcinoma

.avernous !emangioma 3ocal nodular !y er lasia 0odular regenerative !y er lasia *e atocellular adenoma *e atoblastoma

&ost common rimary tumor -oung 'omen -oung 'omen 0o assoc '= estrogens Assoc 'it! trans lantation, .&L=A&L, autoimmune diseases -oung 'omen :trong assoc '= estrogens (+.() > 'ill regress u on discontinuation (eds, usually younger t!an Ny

As# *ig!ly vascular, d# by .) not bio sy 7due to local vascular insult 7due to diffuse vascular insult areas of !y o=normal erfusion .an ru ture during regnancy (!ig! estrogen) massive abd bleed .an resemble 'ell-diff *.. *e atomegaly (abdominal mass) Aggressive tumor, oor (# *ig! A3(

Besembles rimitive !e atocytes &ay include mesenc!yme as 'ell

LB: *.. (nl cells on L, malignant on B), *.. '= t!ickened cords, c!olangiocarinoma '= glands on L, .) !emangioma (took u contrast) TO@IC/M,TA-OLIC/C$OL,0TATIC </O (A)*+,202:/: 2t+* metabolized to to#ic et!anol " acetalde!yde "att' liver > he!atocellular in1ur' (via B+:) .L/0/.AL :teatosis: reversi*le% as# *e atitis: 2t+* on binge, 4aundice= fever=fatigue=lo' a etite, increased A:)SAL) " bilirubin .irr!osis: end stage, s# of ortal *)0, increased risk of *.. Hsually as# +nset at A<y (A)*+L+,:teatosis: large, yello', greasy liver " li id vacuoles in !e atocytes *e atitis: necrotic foci, Mallor' h'aline, (&0s, !ericentral "i*rosis .irr!osis: micronodular, small=firm, ericentral fibrosis, fat, &allorys !yaline (at!ology is similar to alco!olic steattis /ncreased hemosiderin in !e atocytes

2t+* liver dz

0on-2t+* steatosis *emo-

(rimarily due to %& 1U: autoR, increased intestinal 3e

c!romatosis

IilsonFs dz

V1-antitry sin deficiency 1U biliary cirr!osis

u take to#icity " cell deat! $U: assoc '= transfusions, !ig! oral intake autoB, defect of .u metabolism inability to incor orate .u into cerulo lasmin for bile e#cretion to#ic accumulation autoB, folding defect in a1antitry sin to#ic accumulation in liver " lack of rotease (-) in lungs .!ronic, rogressive auto7immune destruction of medium-sized intrahe!atic ducts c!olestasis

.an cirr!osis=$CC, myocardial dysf#n, %&, ar!ro at!y, !y ogonadism )#: !lebotomy, iron c!elation .irr!osis, .0: robs (mainly 1, tremor, syc!osis), Kayser-3leisc!er rings in eyes )#: .u c!elator, ?n (blocks absor tion) 8ariable liver resentation, !i risk *.. (anlobular em !ysema Affects middle-aged 'omen :#: fatigue, ruritis, 4aundice, #ant!omas, steatorr!ea, osteo orosis %#: AMA autoAb, increased alk(, bilirubin, c!olesterol Assoc '= ot!er autoimmune diseases :# as above :trong assoc '= ulcerative colitis /ncreased risk of c!olangiocarcinoma

2levated transferrin saturation

0erum ceruloplasmin is decreased $e!atic and urine ACuB is increased

Accumulation of abnormal misfolded rotein inside !e atocytes, eosino !ils &ranulomatous *ile duct destruction 5eri!ortal in"lammation/"i*rosis Later can !ave cirr!osis

$Ubiliary cirr!osis 1Usclerosing c!olangitis

Long7standing o*struction of e#tra7 he!atic ducts diffuse c!olestasis /nflammation destruction of -OT$ intra=e#tra!e atic ducts

1ile stasis bile lakes (eri ortal inflammation=fibrosis Onion s+in "i*rosis of bile ducts -eads on angiogram

LB: 2t+* !e atitis '= fatty c!anges=&allorys=inflamm, c!olestasis '= bile lakes, (1. '= intense eri ortal inflamm, onion skin fibrosis, beads 5A)CR,A0 1. Anatomy a. (ancreas is a mi#ed gland, e#ocrine makes u JAQ b. 3unctional unit is acinus, '!ic! drains into ductules interlobular ducts main ancreatic duct (Iirsung) common bile duct c. 1ot! acinar (digestive enzymes) and ductal (*.+N) cells contribute to ancreatic 4uice, ;NL=d i. ?ymogens include: try sinogen, c!ymotry sinogen, roelastase, rocarbo#y e tidase, amylase, li ase, nucleases $. 3unction a. :ecretion of ancreatic 4uices necessary for digestion i. .e !alic !ase: vagal stimulation from smelling food acinar secretion ii. ,astric !ase: antral distention -S secretin release $C3/$CO? secretion by ductal cells iii. /ntestinal !ase: duodenal acidification=aa CC. release digestive en:'me secretion by acinar cells N. %isorders a. (ancreas normally rotected via (1) (B+enzymes ($) trans orted in granules (N) try sin in!ibitor accom anies enzymes b. /slet cells are normally s ared in acute, t!us no s# of diabetes c. 0ecrotizing ancreatitis occurs in ;1<Q of acute ancreatitis ts i. ,negs (klebsiella, e coli, enterococcus) ii. )# '= as iration, debridement, ab# A.H)2 (A0.B2A)/)/: Acute inflammation=necrosis=en:'matic digestion of ancreatic tissue due to acinar cell in1ur' /nterstitial ty e: microcirculation reserved, no necrosis 0ecrotizing ty e: !ig! risk of inf#n=mortality +bstructive causes: gallstones (T1, never causes c!ronic) ancreatic cancer, ancreas divisum (anatomical defect, single ancreatic duct never formed) &etabolic causes: !y er),, !y er.a, isc!emia, vasculitis .ongential causes: mutation in try sin (-) V,RY high ris+ o" !ancreatic cancer %rugs: azat!io rine, @-merca /nf#n: more common in develo ing countries <uct o*struction blocked secretions zymogens accum in acinar > fuse '= lysosomes activation of enzymes (try sinogen to try sin) cell in4ury=digestion Local effects: inflamm, "at necrosis (liberated li ase), h'!oCa (from sa onification), !seudoc'st (cavity lined by granulation tissue, filled 'it! necrotic material) :ystemic effects: vessel breakdo'n (elastase, kallikrein, c!ymotry sin), I1. c!emota#is (com lement), %/. (t!rombin), surfactant ( !os !oli ase A$) A*dominal !ain that radiates to *ac+ > aggravated *' "ood inta+e > relieved *' *ending "orward 0=8, lo' grade fever, 4aundice if obstructive etiology Volume de!letion from fluid esca ing Betro eritoneal !emmorage: Grey Turners sign (flank dis.*B+0/. (A0.B2A)/)/: ,radual, ersistent, !rogressive in"lammator' destruction and "i*rous re!lacement o" !ancreatic tissue

%efinition

2tiology

Alcohol (DE) .ystic fibrosis, due to mucous lugs *emoc!romatosis *y er()*

(at!ogenesis

2t+* !y ersecretion ductal t of roteins obstruction gradual fibrosis, acinar atro !y, dilated ducts Autoimmune !ancreatitisF elevated /g,=/g&, A0A, ca sulerim, biliary duct abnormalities

.linical

A<Q as# :#: ain, steatorr!ea, 't loss, 'asting, glucose intolerance Calci"ication common w/ ,tO$% C;

%#=Labs )#

coloration), Cullens sign ( eriumbilical discoloration) 5aral'tic ileus (no bo'el sounds) Cholangitis if gallstone etiology (# de ends on degree necrosis, ot!er organ involvement ,levated serum am'lase% li!ase (N# normal) Abd #ray s!o's sentinel sign (colon cut-off) CT w/ contrast s!o's degree of necrosis, very s ecific Aggressive "luid re!lacement/monitoring 1o'el rest, t!us )(0 Bemove stones :ym tomatic seudocysts require surgery )# com lications

,RC5/,=0 are most sensitive for abnormal ducts Abd #ray s!o's calcifications 3#n tests (e#) lo' *.+N on secretin test (ain D remove inciting rocess (sto drinkingE), analgesics, su!!ress !ancreatic secretion, I!i le :teatorr!ea D li ase su lementation ('= acid su ression), decreased fat intake %& D loss of bot! insulin=glucagons, t!us need tig!t control

O.

.ancer a. b. c. d. e.

f.

g.

<uctal adenocarcinoma makes u J<Q of ancreatic tumors (oor # (AQ Ayr survival), common cause of deat!, t# is usually only alliative Assoc 'it! carcinoma of unkno'n rimary (.H() tumors, mutation in k-ras gene, c!ronic ancreatitis Bisk factors: black males, S@<y, smoking (at!ology i. Hsually involves head of ancreas ii. :c!irrous, i.e. highl' in"iltrative and desmo lastic iii. +riginates from ductal e!ithelium (rarely acinar) .linical i. /f infiltrates common bile duct obstructive 4aundice ii. /f infiltrates duodenum bleeding=ulcers iii. /f infiltrates retro eritoneum erineural s read, ain iv. +t!er s#: 't loss, ne' onset diabetes, migratory t!rombo !lebitis (!y ercoaguable state due to serine rotease) v. .ourvoisierFs sign ( al able non-tender gallbladder, dilated due to tumor obstruction) vi. +ften mets to liver %#: imaging, usually abdominal .), or bio sy ( ercutaneous fine-needle as iration)

&ALL-LA<<,R 1. .!olelit!iasis a. 8ery common, ma4ority of biliary dz b. ,allstones due to eit!er e#cess c!olesterol or bilirubin c. &ost as# (until blockage) and surgery is very successful d. About 1AQ c!oledoc!olit!iasis (stones eit!er de novo, or from ,1, in common *ile duct), similar clinical icture 2)/+L+,O3s - 3orty 3at 3ertile 3emale *emolytic anemia, :: (A)*+,202:/: :u ersaturation of bile '= c!olesterol, form around a nidus of mucus=.a /ncreased biliary un7 con1ugated bilirubin forms around nidus of mucus=.a Cholelithiasis form of lysolecit!in e it!elial in4ury attack by bile detergents necrosis " inflammation &ulti le acute events rogressive mucosal damage &ram neg ra idly s read to due increased ressure Assoc '= c!olelit!iasis .L/0/.AL :#: *iliar' colic ( ain from irritation), 1aundice (from obstruction), "ever .om lications: acute=c!ronic c!olecystitis, c!olangitis, ancreatitis, erf, gallstone ileus (A)*+L+,-ello'-bro'n +void, firm, multi faceted &ost are radiolucent 1lack ty e: small, many, crumbling, radioo aque 1ro'n ty e: fe', soft, fatty, assoc '= inf#n Edema thic+ wall &ucosa may ulcerate em yema :erositis Fibrosis thic+ wall Asc!off-Bokitansky sinuses %ystro !ic calcification H!orcelain gall*ladderI

.!olesterol c!olelit!iasis (igment c!olelit!iasis

Acute c!olecystitis

5acalculous6 form due to serious illness (burns, se sis)

R=G !ain with re"erral to right shoulder Gaundice, fever, >Mur!h's .om lications: se sis, erf , gallstone ileus

.!ronic c!olecystitis

*# of BHW ain )!ick, s!runken gallbladder usually '=calculi 5redis!osition to adenocarcinoma Charcot/s triad: ain, 4aundice, fever Ab# " decom ression necessary 8ery oor (#

.!olangitis Adenocarcinoma

&a4ority due to im acted stone Bare

,0O5$A&=0 1. Anatomy a. =!!er E/? s+eletal muscle, smoot! muscle t!roug!out b. : !incters i. H2:: via crico !aryngeus, inferior !aryn# constrictors 'it! a small s ace in bet'een (im ortant in ?enkers diverticulum) ii. L2:: t!ickening of circular smoot! muscle 4ust belo' crura of dia !ragm c. 8einous drainage i. H er 1=N: :8., mid 1=N: azygos vein, lower E/?F gastric (coronar') v !ortal vein (im ortant in ortal *)0) d. Lym !atic drainage i. H er 1=N: cervical nodes, mid 1=N: mediastinal nodes, lo'er 1=N: celiac=gastric nodes e. Layers i. &ucosa: strati"ied s(uamous e it!elium ii. :ubmucosa: secretory glands, &eissners le#us, and veins iii. &uscularis ro ia: u er 1=N redominately skeletal m, lo'er 1=N redominantely smoot! m 1. /nner circular=outer longitudinal, 'it! Auerbac!Fs bet'een

f.

g.

$.

N.

3unction a. Trans"er: movement of food from oro !aryn# to eso !agus b. )rans ort: movement of food do'n t!e eso !agus to stomac! iJ 5rimar' !eristalsis (swallow7initiated)% secondar' (stretch7initiated)% tertiar' (uncoordinated) c. %efintions i. As iration D breat!ing in food ii. %ys !agia D difficulty s'allo'ing=food gets stuck 1. )ransfer: !ard to get food to eso !agus (e#) stroke, botulism, &,, oly=dermatomyositis, ac!alsia or ?enkerFs $. )rans ort: motor and mec!anical d=o iii. +dyno !agia D ain '!en s'allo'ing, t# '= myotomy (incision of s !incter) or 1oto# d. .linical tests of f#n i. &anometry: robe can measure c!anging ressure in t!e eso !agus, *est "or motor d/o 1. 0ormal 'ould s!o' a rogression of muscular contractions " o ening of L2: at time of s'allo' ii. * monitoring: measure * c!anges in eso ! over time, *est "or re"lu# studies and to r/o cardiac etiolog' %isorders a. &otor %isorders (functional) %# 1arium #ray (dilation) &anometry d# 2,% necessary to rule out seudoac!alsia 1arium #ray (corkscre') &anometry d# (but rarely catc!es it) &anometry &anometry Lo' ressure 'aves .L/0/.AL A!eristalsis in eso!hagus ;ailure o" L,0 rela#ation %ys !asia to bot! solids=liquids <ue to loss o" Auer*ach/s !le#us (seudoac!alsia D stomac! tumor destruction of Auerbac!s (redis oses to ,2B%, reflu#, 1arrettFs 0imultaneous% high am!litude% non7!ro!ulsive contractions inters!ersed with normal !eristalsis %ys !asia :# 'orsenened by emotional stress, very !ot=cold liquids 2#tremely !ig! ressure eristalsis .!est ain .ollagen de osition (blue in ic) in smoot! m distal a eristalsis " incom!etent L,0 &astroeso!hageal re"lu# is main com!lication

ivJ )o serosa /nnervation i. (: via vagus ii. Auberbac!Fs myenteric le#us coordinates eristalsis iii. &eissenerFs submucosal le#us is sensory .linical tests of anatomy i. 1arium eso !agogram: M-ray used to visualize anatomy, non-invasive, no com lications ( revious age) ii. 2,%: endosco e visualizes mucosa detail of u er ,/ 'it! bio sy=t!era eutic ca abilities iii. 2ndosco ic H:: visualizes t!e layers of ,/ including mucosal and e#tramucosal, *est "or tumors (bio sy ca abilities)

Ac!alsia

)# 5neumatic dilation (s lits L2: muscles) M'otom' 1oto# Beassurance :moot! m rela#ants :ame as above

%iffuse eso !ageal s asm 0utcracker eo !agus :cleroderma

b.

&ec!anical %isorders (obstructive) i. (rogressive dys !agia due to narro'ing of lumen ii. :olids 'orse t!an liquids iii. +ften acute resentation due to im action of food bolus %# 1arium #ray, 2,% 1arium #ray, 2,% 1arium #ray, 2,% 1arium #ray, 2,% 1arium #ray, 2,% .L/0/.AL Ac(uired "i*rous thic+ening o" eso!hagus (submucosa) Can *e due to chronic in1ur' (&,R<)% scleroderma , caustics .oncentric constricture :!elf-like rotrusions of mucosa in u er eso !agus Iomen SO<y (lummer-8inson: 'eb, 3e defcFy anemia, c!eilosis, glossitis :c!atzki rings 9 a 'eb near ,2 4unction, assoc '= !iatal !ernia Abnormal ouc!=sac from eso !ageal 'all Ken+er/s <iverticulum occurs 4ust above H2: due to incom lete rela# of H2:, food accum neck mass=as iration )raction diverticula D mid-eso !agus, as a result of nearby scar tissue ulling on normal eso !agus 2 i !renic diverticula D results in nocturnal fluid regurgitation )!in, non-canalized ortion ro#imal=distal ouc!es +ften occur at level of bifurcation +ften co-e#ists '= ot!er congenital abnormalities (oly!ydramnios in utero, severe coug!=regurg at first feeding Abnormal connection= assage'ay bt' eso !agus=trac!ea .ommon roblem is as iration neumonia Iidened s ace bt' muscular dia !ragmatic crura and eso !agus &ost common ty e rotrusion of stomac! above dia !ragm, abnormal L2:, reflu# Iidened s ace bt' muscular dia !ragmatic crura and eso !agus :e arate ortion of stomac! entering t!ora# +ften due to revious surgery )# %ilation (bougies=balloons) .!emo, surgery, stent %ilation (bougies=balloons) %ilation (bougies=balloons)

:trictures, stenosis 0eo lasms Iebs Bings %iverticula

Atresia

1arium #ray

3istula ( ro#=distal) :liding !iatal !ernia (ara eso !ageal !iatial !ernia 8J

1arium #ray .ommon, $<Q adults Assoc '= increasing age

,so!hageal varices

a. b.

&ost im ortant clinically: lo'er 1=N of eso !agus and u er stomac! is drained by gastric veins to ortal system (ortal *)0 backu and dilation of submucosal venous le#us in stomac!=eso !agus 1. 2so !ageal varices 9 4ust above ,2 4unction, can e#tend u $. ,astric varices 9 e#tend from eso !ageal varices or arise inde endently

A.

@.

.om lications: bleedingE EJ Accounts "or E/? o" all deaths in cirrhotic !ts $. .orossion !y ot!esis (reflu# causes erosion) N. 2# losion !y ot!esis (e#cessive *)0 from ortal *)0) d. :#: !ematemesis and melena (lo'er ,/ blood is !ematoc!ezia) e. )#: hemod'namic sta*ilit'% sclerot!era y, ligation 2so !agitis ( rimarily ,2B%) a. Any sym tomatic condition or !istologic alteration assoc '= gastric acid reflu# 1. 8ery common, !ig!est rates in regnant 'omen b. Beflu# eso !agitis is at!ologic definition, i.e. ,2B% resulting in lesions identified by endosco e 1. &icrosco ically see elongation of a illae, inflammation '= eosino !ils c. %ue to e# osure to stomac! acid via L2: incom etency, increased abd (, sliding !iatal !ernia, delayed gastric em tying d. :#: !eartburn, acid taste in mout!, dys !agia e. %#: endosco y s!o's red, inflamed mucosa f. .om lications: eso !ageal ulcers=strictures=obstruction, c!est ain mimicking acute &/, 1arrettFs eso !agus, bleeding g. )#: lifestyle c!anges (quit smoking, 't loss, avoid big meal before bed) " !arm (((/s, *$ blockers, antacids) !. +t!er causes seen in immunoC (e#) !er es ( unc!ed out lesions '= multinucleated inclusions), .&8, candida 1. Bare causes: caustics, radiation, allergy 1arrettFs 2so !agus a. /rritation columnar meta!lasia re laces squamous in distal eso !agus (an ada tive res onse) b. :een in same o ulation as ,2B% (considered a consequence) but far more common males c. %#: atc!y red areas e#tending above ,2G on endosco y, glands '= go*let cells in eso !agus d. .om lications: 83# increased ris+ o" eso!hageal adenocarcinoma Bisk factors: synergistic effect of 2t+* " tobacco, ,2B%=1arrettFs, ac!alsia )#: surgery or c!emo=radiation (cure rates oor due to infiltrative nature " late resentation), dilation "or !alliation :WHA&+H: .2LL .AB./0+&A &en S A< *ig!er in AA and smokers 5ro#imal eso!hagus &ets common due to ric! venous=lym !atic su 0ests of squamous e it!elium A%20+.AB./0+&A &en SA< :trongly assoc '= 1arrets <istal eso!hagus, sometimes stomac! &ets common due to ric! venous=lym !atic su ,lands '=in mucosa

c.

R.

.ancer a. b.

/ncidence :ite of involvement *istology

ly

ly

LB: nests of :.., endosco y of tumor at ,2G, 1arrettFs eso !agus endosco y, 12 '= nl squamous on B, adenocarcinoma 0TOMAC$ 1. Anatomy a. .ardia, fundus, antrum, body, ylorus i. Antrum: long its, 0+ glands ii. 1ody: s!ort its, ver' glandular ( ic at rig!t) iii. ,rossly: rugae, look for t!ese to id stomac! via endosco e b. .ell ty es iJ )O go*let cells ii. &ucous cells: line entire surface, secrete mucus and e sinogen iii. (arietal cells: glands in fundus and body, secrete *.l and intrinsic factor iv. .!ief cells: glands in fundus and body, secrete e sinogens v. 2nteroendocrine cells: secrete somatostatin, serotonin, !istamine (bind *$ B on arietal cells * release) vi. , cells: secrete gastrin c. /nnervation i. 2#trinsic: vagus and s lanc!nic nerves ii. /ntrinsic: myenteric le#us iii. &ec!anoB: ro#imal stomac! D sense distenion, distal stomac! D senses contractions $. 3unction a. %igestion i. .e !alic !ase: sig!t, taste, smell of food or act of c!e'ing=s'allo'ing stimulates via vagus gastrin * release ii. ,astric !ase: gastric distension or vagus gastrin * release iii. /ntestinal !ase: digested rotein enters duodenum ,-cells of duodenum and 4e4unum secrete gastrin * release b. .ontractile activity i. :lo', sustained @ minute contractions (ma4ority) " ra id, !asic contractions of a fe' seconds ii. (ro#imal 9 vagovagal refle# (res onds to c!anges in volume '!en eating (rela#es) and distention (accommodation)) iii. %istal 9 acemaker contractions every $< seconds, can be modulated iv. (ylorus 9 narro'ing of stomac! resistance to flo' '!ic! revents assage of large food ieces N. %isorders

a.

b.

Acute erosive gastritis i. Acute, direct damage (or interru tion of blood su ly) to mucosa acute !emorr!age, erosion or ulcers ii. 2tiology 1. ,tO$ by direct cellular in4ury 2. )0AI<s block rostaglandin synt! decreased mucous roduction N. 0evere !h'siologic stress (ma4or burns, surgery, multisystem organ failure) due to decreased blood flo' a. Curlings ulcers occur after severe burns 4. *ead trauma '= /.( increased vagal tone increased * secretion Cushings ulcers 5. (ost-gastric surgery bile reflu#, '!ic! can break do'n mucosal barrier iii. .linical: 0=8 " e igastric ain, d# by 2,%, t# is su ortive iv. (at!ology: erosions (limited to mucosa) " ulcers (e#tend into muscularis ro ria), also edema=!y eremia= etec!ia .!ronic gastritis i. .!ronic inflamm " loss of gastric glands " mucosal atro !y ii. 2tiology EJ $elico*acter !'lori in"#n (vast ma1orit')% usuall' in antrum CJ Autoimmune% usuall' in *od'/"undus N. /) /: 0+) AL.+*+L iii. * ylori 1. ,- lives in mucous layer (non-invasive), !as flagella for motility in mucus " urease roduces 0*O to buffer acid $. 8ery common, around A<Q of o ulation is infected 'it! *. ylori but most are as'm!tomatic a. *o'ever, *. ylori is ma1or ris+ "actor "or !e!tic ulcer disease N. %#: breat!ing test (0*O), culture, .L+", /g, titers for * ylori, stool test O. (at!ology b. 2arly: 5M)s at *ase ( it abscesses), diffuse lym !os, org can be seen in mucus c. Late: atro !y of mucosa, intestinal meta!lasia (goblet cells) cancer A. )#: tri le t!era y (see !arm lectures) 9 $ ab# " ((/, ;P<Q effective iv. Autoimmune gastritis 1. Auto7A* against !arietal cells !y oc!lor!ydria, mucosal atro !y a. Loss of ,/3 !ernicious anemia (cannot absorb 8it 11$) $. %#: elevated gastrin (no *.l negative feedback), anti /3 Ab, bio sy N. (at!ology: mainly !lasma cells O. )#: in4ected 11$

LB: !y eremia of acute gastritis, neutro !ils in acute gastritis, * ylori seen in mucous, it abcess, A1+82: /3 of anti arietal cell Ab c. (e tic ulcer disease i. (resence of c!ronic ulcers '!ic! induce intense inflammatory=immune res onse (/L$, /L@) ii. Location 1. :tomac!=gastric ulcer: larger, X lesser curvature, !ain ?3m !ost7meal )OT relieved *' eating $. %uodenum=duodenal ulcer: smaller, in 1st ortion, !ain *tw meals > relieved *' eating iii. 2tiology: ma4ority caused by $J!'lori, also by 0:A/%s (.+M $ less bad), gastrinoma iv. (at!ology: ulcers e#tend into submucosa, can erode all t!e 'ay t!roug! ( erforation) 1. 3our layers D necrotic debris " inflamm " granulation tissue " scar tissue v. %#: endosco y " bio sy to r=o cancer vi. ALARM s#: anore#ia, 0=8, 't loss, ,/ bleed vii. .om liations: bleeding, erforation '= "ree air under dia!hragm viii. )# 1. Lifestyle c!anges D quit smoking and drinking and being fat and lazy $. ((/s (most effective), *$ blockers, bismut!=antacids=:ucralfate, eradicate * ylori N. Young/health' w/ 5=< > !ositive $ !'lori can *e t# em!iricall' , i.e. no need for bio sy i#J Kollinger7,llison s'ndrome O. )riad of severe 5=<% gastric acid h'!ersecretion% gastrinoma (tumor usually in !ead of ancreas) A. %#: secretin stimulation test ( arado#ical rise in gastrin level after /8 infusion), elevated gastrin '!ile fasting @. :#: (H% and=or c!ronic diarr!ea (damage of bo'el from e#cessive acid) R. )#: !ig!-dose ((/, octreotide (somatostatin analogue)

LB: s!allo' gastric ulcer, duodenal ulcer, loss of mucosa in ulcer, free air under dia !ragm '= erf O. .ancer a. Adenocarcinoma ( ic at rig!t) i. Bisk factors: $ !'lori, diet !ig! in nitrates (cured=smoked foods), men SA<y, lo' :2:

ii. iii. iv. v. vi.

5# most related to de!th o" invasion , usually resent at advanced stage :#: 't loss, early satiety, ain, bleeding, vomiting %#: Virchow node 9 su raclavicular sentinel node, often t!e first manifestation )#: surgery, t# * ylori

b. c.

)y es 1. IntestinalF intestinal meta lasia, i.e. glands '= goblet cells $. <i""use in"iltrating/signet ring: single tumor cells 'it! intracyto lasmic dro of mucin us!ing nucleus to side a. %iffuse infiltrative attern leat!er bag a earance aka linitis lastica ( ic belo') Lym !oma (&AL)oma) vii. :trong assoc '= * ylori, may resolve if inf#n eradicated viii. 0o normal mucosa, i.e. all of mucosa !as lym !ocyte infiltrate ,astrointestinal :tromal )umor (,/:)) i#J c7.it mutation (!ancreatic cancer is +7ras)

0MALL I)T,0TI), 1. Anatomy a. @ meters of absor tive surface from ylorus to ileocecal valve b. Ligament of )reitz links to osterior abd 'all c. Layers i. &ucosa: folds of villi ( licae circulares) 'it! microvilli ( lasma memb ro4ections) on to , sim le columnar e it!elium 1. Lamina ro ria 9 some inflammatory cells, blood vessels and lacteals, cry ts of e it!elium ii. :ubmucosa: &eissnerFs le#us, -runner/s glands (duodenum only), (eyerFs atc!es (distal ileum) iii. &uscularis e#terna: Auerbac!Fs le#us (bet'een inner circumferential, outer longitudinal) iv. :erosa d. .ells i. 8illi: goblet cells (secrete mucus) " enterocytes (absorbtive) ii. .ry ts: above " anet! (enzymatic) " endocrine (..K, serotonin, 8/() " stem cells $. 3unction a. I!atFs absorbed '!ere7 i. :tomac!: 2t+*, 3e (acid facilitates), 11$ binds /3 ii. %uodenum: 3e, .a, 1-vitamins (e#ce t 11$) iii. Ge4unum: aa, 33A, monoglycerides iv. )erminal ilium: 11$, con4ugated bile salts (along '= fat, fat soluble vitamins) 1. 1acterial overgro't! breaks u con4ugated bile salts malabs of fat, fat soluble vitamins v. .olon: o#alate, fluids, electrolytes b. A#es i. 8ertical a#is: cry t to villus ti 'it! a o tosis=re lacement, functional absor tion, !enoty ic s'itc!ing ii. Longitudinal a#is: P<Q of digestive absor tion is in initial art of intestine c. (!ases of absor tion i. Luminal !ase: c!emical alteration of nutrients ability to absorb, req ro er *, ancreatic zymogens, bile acids ii. /ntestinal !ase: occurs at level of enterocyte, req sufficient surface area 1. )ranscellular route a. 2#tracellular (luminal) enzymes in glycocaly# breakdo'n nutrients for absor tion i. %isacc!aridases (for 0a-glucose cotrans or), li ases (micelles), e tidases (0a-aa cotrans ort) b. /ntracellular c!ylomicron assembly, e# ort of nutrients $. (aracellular route a. A ical u take of )a/glucose via 0a=glucose cotrans ort dra's 0a=glucose t!roug! cell and absorbed b. +smotic gradient ulls in 'ater from lumen aracellularly c. &L=CO0, must *e given with )a "or ra!id $C3 re!lacement since t!e trans orter requires bot! N. &alabsor tion a. 2tiology: surgical resection, bacterial overgro't!, ancreatic insufficiency, stomac! damage, intestinal damage b. :# i. Ieig!t loss, muscle 'asting, edema ii. %iarr!ea, cram s, flatulence iii. Anemia (3e deficiency !y oc!romic microcytic, 1P macrocytic !y ersegmented olys, 11$ ernicious anemia) iv. Coagulo!ath' due to 8it K deficit v. Osteo!ath' due to 8it %, .a deficits vi. Benal o#alate stones 1. 0ormally o#ylate 4oins '= .a in intestine and removed toget!er, '!en bile acids arenFt reabsorbed (due to no ileum or bacterial overgro't!), 33A arenFt abs 33A bind .a free o#ylate, '!ic! is t!en reabsorbed by colon vii. ,allstones due to decreased bile salt reabsor tion increased c!olesterol in bile concretions c. &anifestations i. 3at absor tion is com le#, t!us malabs syndromes 'ill usually result in steatorrhea (!allmark of malabs) 1. /n lumen, li ases from ancrease 33A and glycerol 2. 33A bind bile salts absorbed, re-esterified back into ),, ackaged as c!ylomicrons, absorbed into lacteals a. 2#ce tion: s!ort=medium c!ain ), not ordinarily abundant in diet, but are absorbed directly into intestinal ca illaries ( ortal v) '=o any li olysis=micelle=c!ylomicrons necessary N. %#: :udan stain, or by LC7hr stool collection w/ li!id (uanti"ication (S$<g abnormal) ii. 8it 11$ absor tion 1. Acid releases 11$ from food, t!en bound to B factors $. (ancreatic enzymes release B factors so it can bind ,/3, com le# is absorbed in terminal ileum a. 1acterial overgro't! breaks com le#, '!ic! can minimize absor tion d. 1acterial overgro't! i. .an decrease 11$ and bile salt reabsor tion ii. ;alse results o" <7#'lose test (bacteria metabolize #ylose, t!us removing it, so test 'ill falsely im ly absor tion) iii. %#: early eak in !ydrogen breat! test, colony count, ab# trial, imaging

e.

iv. )ests i. ii. iii. iv.

.auses: achlorh'dria% gastric surger'% motilit' disorders% diverticula , loss of ileo-cecal valve, scleroderma 0utritional tests include .1. (for anemia), albumin levels (lo' rotein absor tion), vitamin deficiencies .!eck stool for ova= arasites .!eck ancreas: secretin stimulation s!ould result in !ig! *.+N secretion ( arado#ical inc of *.l in gastrinoma) /ntestinal vs ancreatic a. %-#ylose test: ancreatic enzymes are not required for #ylose absor tion (so :/ roblem 9 lo' HB/02 #ylose) *ydrogen breat! test: '= dissac!Fase deficiency, sugar remains in gut > metabolized by bacteria * release, blo'n off

O.

v. %isorders a. .ongenital abnormalities

:tenosis, atresia &alrotation +m !alocele

,astrosc!isis

%u lication &eckelFs diverticulum

:/)2 A332.)2% %uodenum most common .om lete (atresia) vs artial (stenosis) obstruction /m ro er rotation of gut '!en returning into embryo, no fi#ture via ligament of )rietz %efective formation of some abdominal musculature !erniation of abd contents into membranous sac :till covered by skin, umbilical cord is above defect Abdominal 'all defect due to absent ortion of abdominal 'all e#trusion of t!e intestine %efect is beside umbilical cord ( araumbilical) /leum most common Most common malformation of ,/ 8estigial remnant of vitelline duct ('!ic! connects umbilicus=bo'el) blind ouc! in ileum O"ten ecto!ic tissue (stomac!= ancreas)

.+0:2WH20.2: +bstruction (erforation meconium eritonitis *ig! c!ance of volvulus strangulation of bo'el necrosis I!en assoc '= ot!er anomalies (common), mortality is increased $I&$,R MORTALITY T$A) &A0TRO0C$I0I0 (# de ends on viability of intestine, degree of defect 0ot assoc '= ot!er anomalies cystic structures Bule of $s: '=in $ ft of /.8, $Q of o ulation, $&:13, $Q !ave s# (e tic ulceration (es '= ecto ic gastric mucosa), bleeding anemia, acute abdomen (intussusce tion D colla se of art of intestine)

b.

&any stages can be affected, e.g. im aired intraluminal digestion, absor tion, fermentation %232.) Luminal !ase defect (A)*+,202:/: autoB mutation in .3)B (3A<J, c!rR) dysfunctional .l trans ort t!ick secretions ancreatic insufficiency (clogged ducts) %#=(A)*+L+,Meconium ileus in neonatal !eriod %# by elevated s'eat .l (ancreatic issues begin in utero Lung issues begin after birt! :#=.L/0/.AL Most common lethal autoR d: s'eat glands: oor reabs of 0a.l ancreas: viscous secretions obstruction anc insu""ienc' steatorr!ea, acinar necrosis lungs: inc 0a=*$< reabs t!ick, de*$< mucus neumonia (via seudomonas), bronc!iectasis %iarr!ea, cram s

.ystic fibrosis

Lactase defcFy

&icrovillus defect (lack enzyme) /ntestinal, surface area defect

.eliac dz

Hsually acquired (commonly AA) /nsufficient lactase lactose accum osmotic diarr!ea Autoimmune r#n to gliadin (gluten rotein) found in '!eat=barley=rye enterocyte damage flattening of villi less :A and malabsor tion autoB mutation in A o1 interferes 'it! c!ylomicron (A o1OJ) synt!esis and t!us fat=vit-KA%2 absor tion :ystemic inf#n ). '!i elii bacteria

Abetali oroteinemia I!i leFs dz

/ntestinal, metabolic f#n defect /ntestinal, surface area > cellular e# ort defect 1ile acid deficiency, surface area defect

0ormal !istology %#: * breat! tests lactose (orgs break it do'n), tolerance test 8illous flattening, cry t !y er lasia, inflamm Affects mainly ro#imal :/ (s ares ileum=L/) abnormal lactase test %#: celiac anel, "auto-Abs 2 it!elial cells ale (engorged in fat since absorbed but cant be ackaged into c!ylomicrons) 5ale macro!hages 0o significant inflammation %#: (A: staining organisms

Most common mala*s d/o %iarr!ea=malnutrition /ncreased risk of intestinal cancers

(redictable s# based on fat and fat soluble vitamin malabs Arthritis% mala*sor!tion% l'm!hadeno!ath' %e ends !o' muc! 'as resected S1m bile acid malabs syndrome 9 loss of bile acids and loss of fats Ileal resection -EC deficiency Acute diarr!ea lasting S$ 'ks (usually viral) )# '= lactose free diet 82B- common )# 'it! metronidazole :kin=res iratory=,/ s#

:!ort bo'el syndrome

Besected bo'el 5s!ort bo'el syndrome6 markedly reduced :A for absor tion (rolonged diarr!ea damaged e it!elium secondary lactose malabsor tion %rinking contaminated 'ater

(ostenteritis syndrome ,iardia .o'Fs milk allergy A. .ancer a. b. c.

(rotozoan can be seen in lumen (non-invasive) 8illous atro !y, eosino !ils

(rimary cancer rare, mets common 1enign (adenoma, li oma, leiomyoma) SS malignant Carcinoid is most common 0I malignanc' i. 2ndocrine tumor t!at secretes serotonin ii. :lo' gro'ing, lo' grade, rarely met, usually as# iii. Location matters D ileum 'orst # b=c of increased c!ance to met to liver carcinoid sydrome

iv.

.arcinoid syndrome 1. :#: tricus id insufficiency, ulmonic stenosis, skin flus!ing, diarr!ea (last t'o due to !ig! serotonin) 2. (at!o: infiltrative mass '= desmo lasia obstruction, neurosecretory granules (dense core w/ halo) N. )#: surgery, octreotide (in!ibits serotonin release)

LB: normal vs celiac dz '= flattened villi, giardi organisms, nests of carcinoid cells, 2& of neurosecretory granules (left side) COLO) 1. Anatomy a. .ecum, ascending, transverse, descending, sigmoid, rectum b. Iall structure: mucosa (no folds), lamina ro ria (no l'm!hatics), taenia coli (longitudinal m outside !austra) c. &ucosa: no villi, cells include cry t ( roliferative), surface (many go*let), endocrine, (anet! in B colon only (if L 9 metastasis) $. 3unction a. Beabsor tion of remaining 1<Q of 'ater and electrolytes i. /f voluminous diarr!ea, t!ink :/ cause b. 3ormation and storage of feces c. &icrobial fermentation d. :ite of o#ylate absor tion in malabsor tion syndrome +0L- (itFs a at!ological consequence) N. %isorders a. .ongenital i. *irsc!s rung disease: de"ect o" migration o" ganglion cells aganglionic segment beginning at rectum, e#tending ro# lack of (-) in ut tonic contraction " a eristalsis functional obstruction " dilation of ro#imal segment 1. Assoc '= %o'nFs syndrome, &S3 $. %elay in meconium (normally '=in $O! of birt!) and c!ronic consti ation N. %# via bio sy D suction shows a*sence o" Meissners , full-t!ickness s!o's absence of Auerbac!s b. /nflammatory bo'el disease (H.=.ro!ns) i. /dio at!ic c!ronic rela sing inflamm of intestine 1. 3amilial association: genetic redis osition if *LA-%B1 (.ro!ns) or *LA-%B$ (H.) $. (eak resentation 1A-$Ay, more common in '!ites=females ii. Assoc '= sclerosing cholangitis 9 inflamm=fibrosis of bile ducts 1. :#: 4aundice, ruritis $. (atc!y, t!us not often seen on bio sy, but onion s+in "i*rosis is diagnostic N. .!aracteristic *eading o" *arium on ,RC5 H. .B+*0: :#: abdominal ain, 0=8=%, !ematoc!ezia, 'eig!t loss, to#ic megacolon 2#traintestinal s#: olyart!ritis, sacroilitis, ankylosing s ondylitis, eryt!ema nodosum (subW fat inflammation), clubbing Continuous inflamm in rectum, e#tending ro#imally 0egmental (s+i! lesion)% granulomatous inflamm any'!ere 0clerosing cholangitis -S inflammation of !e atic bile ,allstones, .a-o#ylate kidney stones ducts, increases risk for c!olangiocarcinomaY im lies UC Limited to the mucosa (not transmural) Transmural destruction 3riable, edematous, hemorrhagic mucosa &ranulomas are diagnostic 0+ 'all t!ickening=strictures Thic+ened wall strictures Large% *road ulcers <ee!/linear "issuring ulcers 5seudo!ol'!s , cry titis .ree ing fat, serositis, cry titis %ys lasia (decreased goblet cells) adenocarcinoma .obble-stoning due to irregular ulcers A0.A " :urveillance colonosco y for lo' grade dys lasia to catc! colorectal cancer &esalamine (A-A:A), corticosteroids, colectom' is curative in severe cases :urgery: fulminant disease, erformation, cancer A0.A rarely " &esalamine, corticosteroids, Ab#, anti-)03 monoclonal Abs (immunomodulators), strong immunosu resives (azat!io rine, @-merca to urine, &)M) :urgery is not curative, !ig! reoccurance rate :urgery: fulminant disease, erformation, cancer

:!ared .linical (at!ology

&olecular )#

LB: normal colon, (a) ulcerative colitis = (b) seudo oly s, mucosal inflamm of H., cry t abscesses, transmural inflamm of .ro!nFs c. (oly s i. 1enign (0+0-neo lastic) 1. *y er lastic a. /f isolated find, no need for colonosco y

d.

b. 8ery glandular (goblet cells), serrated mucosa *amartomatous a. :een in (eutz-Geg!ers oly osis, 4uvenile oly osis b. Guvenile oly : distal oly s seen in rectum, no risk of malignancy c. :moot! surface, large dilated glands filled 'it! mucin N. /nflammatory: seudo oly s seen in /1% ii. (re-malignant=dys lastic 1. Adenomatous ty e (aka 5adenomas6): lo'-grade, but !ig!ly assoc '= adenocarcinoma a. %+2: 'arrant colonosco y b. 8illous subty e (finger-like) are larger, sessile, '= greater risk to develo into carcinoma i. .igar-s!a ed !y erc!romatic nuclei cJ Invasion into lamina !ro!ia and muscularis mucosa o" colon is still considered in situ% */c lac+ o" l'm!hatics means virtuall' no metastatic !otential iii. /f com lete, endosco ic resection is curative *ereditary oly osis i. All are auto< inheritance ii. Guvenile oly osis 1. %ozens-1<<s of hamartomatous !ol'!s in +ids in distal &I $. &oderately increased risk of colon cancer iii. (eutz-Geg!ers oly osis 1. :)K11 c!r1P mutation $. $amartomatous !ol'!s throughout entire &I N. 5igmented s!ots on li s=buccal mucosa O. /ncreased risk of ot!er ty es of cancer A. 1egin surveillance at age 1< iv. *0(.. 1. Hsually found in B colon v. 3amilial adenomatous oly osis (3A() EJ A5C tumor su!!ressor gene mutation 2. Bequires second !it mutation of good co y of A(. gene adenoma carcinoma N. 1<<Q develo colon cancer, t!us ro !ylactic colectomy O. ,ardner :yndrome D includes skin and teet! roblems A. )urcot :yndrome D includes brain tumors MJ $'!ertro!h' o" retinal !igment e!ithelium $. Adenocarcinoma iJ Most common tumor o" &I is colon cancer ii. Bisk factors: long-standing untreated /1%, oor diet, increased T adenomas, family !# iii. :#: obstruction, ain, bleeding, anemia, tenesmus iv. &or !ology: irregular% disorgani:ed% desmo!lastic r#n v. )y es same as gastric 1. /ntestinal ty e: very mucinous, its like a goblet cell roliferation $. %iffuse infiltrating: signet ring ty e (rare, oor (#) .arcinoid tumor i. Iell-differentiated endocrine neo lasm, usually in a endi# ii. Ileal carcinoids most likely to metastasize iii. :erotonin increased, but most are asym tomatic iv. .arcinoid syndrome ( resents 'it! liver mets) 1. 8asomotor disturbances (flus!) $. /ntestinal !y ermotility (diarr!ea, cram s, vomiting) 3. (ulmonic stenosis bronc!oconstriction (ast!ma-like) O. )ricus id insufficiency ,enetic cancers :(+BA%/. 3e' 294 o" colon cancers Age @A Hnkno'n, 7A(. gene &ultifactorial none
)o bottom: 3A(, ulcerating tumor, cro'ded nuclei in adenocarcinoma

O.

.ancer a.

b.

c.
T adenomas 3requency 2 idemiology &olecular /n!eritance Assoc tumors

*0(.. 3e' Iit! mutation, J<Q lifetime risk of cancer Age N< %efect in mismatch re!air genes auto% Lync! // !as numerous e#tracolonic sites

3A( (t develo s 1<<s=1<<<s of oly s Iit! mutation, 1<<Q risk by age OA Age $< &utation in A5C gene auto% $'!ertro!h' o" retinal !igment e!ith Villous adenoma o" duodenum

d. e.

0creening guidelines N LA- gu' said to +nowOOO ( g 1PA of notes) :taging of ,/ carcinomas i. &oderately differentiated is most common grade resentation ii. )&0 classification is most im ortant # indicator 1. I!en distant mets are resent, Ay survival ZAQ

I);,CTIO=0 <IARR$,A 1. Acute: Z$', ersistent: $-O', c!ronic: SO' a. P<Q of acute cases are infectious b. +t!ers: medications, /1%, tumors, isc!emic colitis, diverticulitis $. &ec!anisms a. )on7in"lammator': usually affects :/, co ious 'atery stools, de!ydration common, (-) blood=fecal leukos=tenesmus i. )o#in-mediated (e#) vibrio c!olera, 2)2. (travelers)

3.

ii. Altered villous absor tion (e#) 2(2., giardia, cry tos oridium, rota=norovirus (viral villous ti blunting) In"lammator': usually affects L/, mucoid=bloody stools, de!ydration uncommon, (") blood=fecal leukos=tenesmus i. &ucosal invasion (e#) s!igella, salmonella, cam y ii. .ytoto#in (e#) c diff cJ 0'stemic i. :almonella ty !i ( ty !oid fever) ii. 0on-ty !oid salmonella ( gastroenteritis) 2nteric fever: intestinal inf#n caused by a variety of bacteria sustained, systemic febrile illness a. PAQ of cases are due to salmonella ty !i b. :AL&+02LLA )-(*/ :AL&+02LLA 0+0-)-(*/ +0L- e#ists in !umans, t!us onl' !assed via direct/indirect ?oonotic, t!us s reads from animals ( oultry, re!tiles) to contact w/ contaminated human "eces !umans /ngested ad!eres to :/ mucosa invades via ty e /// secretion (in4ects rotein directly into !ost cell) membrane ruffling (actin rearrangement) and internalization via & cells !agoFed by &C of (eyer atc!, '!ere it re licates Iit! s ty !i, bacteria s read to lym ! nodes t!en bloodstream bacteremia " onset of s# (1) dissemination to liver, s leen, bone marro' " c!ronic state if gets into gallbladder Iit! 0+0 s ty !i, locally invades but rarely causes bacteremia local inflammatory res onse and fluid secretion diarr!es 1lunted villi, eyer atc! s'elling=ulceration=s!ar borders, &C '= bacteria, liver 5ty !oid nodules6 (small necrotic foci in '!ic! !e atocytes are re laced by leukocyte aggregates) $igh grade% sustained "ever "or PCw ,asteroenteritis=colitis Abdominal ain=distension /3 gets in blood inf#n of vascular sites, es aortic aneur'sms %iarr!ea +B consti ation .0: c!anges (e#) confusion, delirium Rose s!ots .om lications: intestinal erf=!emorr!age= eritonitis, endocarditis, liver abscess, meningitis, se tic 4ts 1L++% c# (stool=urine=skin=1& may also be ") :)++L c# Nrd gen ce !alos orin, quinolone (resistance in /ndia) )o a*# i" uncom!licated, self-limiting

Bout e (at!o

&icro :#

%# )# O.

+t!er common causes 2(/%2&/+L+,&ost common bacterial cause of travelers 2 idemic infantile (!os ital nursery) +1AR:*R most common Hndercooked ground beef (A)*+ *eat labile=stable to#in .o ious 'atery diarr!ea 2ffacement of brus! border :!iga-to#in .o ious bloody diarr!ea '=o fecal leukos=fever Assoc '= $=0 ( eds B3) %# 0+) available in routine lab 0+) available in routine lab O)LY e coli in routine la* (sorbitol-negative) )O a*# (may *H:) )# Ci!ro"lo#acin% *actrim

2)2. 2(2. 2*2.

2ntero/nvasive 2nteroAggregative :!igella 8ibrio c!olera

rare rare : sonnei (most common) : fle#neri (A/%:) (oorly cooked s!ellfis!

.am ylobacter . diff ,iardia 0orovirus

Botavirus

&ost common bacterial /nfected oultry *os ital-acquired from receding ab# use &ost common arasitic 3ecal-oral, contam 'ater DE MO0T common cause o" diarrhea Iinter, e idemic, adults and kids Iinter, s oradic, kids

:!iga to#in dysentery, *H: .!olera to#in increase cA&( active secretion of .l ('ater follo's) diarr!ea " de!ydration ,uillian-1arre .ytoto#in inflamm colitis " !seduomem*ranes 0o invasion (rolonged diarr!ea Lasts only 1-$d 53ood oisoning6 Lasts O-Jd

0+) available in routine lab 0+) available in routine lab Available in routine lab via stool culture Available in routine lab via stool culture

Ab# if severe (s!ortens) Aggressive re!ydration Tetrac'cline/a:ithrom'cin (shortens) 2ryt!romycin &etronidazole, vancomycin &etronidazole

Available in routine lab via stool culture Available in routine lab via stool ,IA Available in routine lab via stool e#am "or c'sts 0+) available in routine lab +nly state labs=.%. Available in routine lab via stool ,LI0A

0Y0T,MIC </O 1. &any ,/ factors '!ic! redis ose for systemic conditions a. Large and com le# blood su ly b. Largest B2: system in body ((eyers atc!es, /gA, &AL)=,AL)) c. Autonomic nervous system d. 2#tensive smoot! m e. 0utrition D feeds t!e body $. &etabolic = 2ndocrine a. %iabetes i. <ia*etic neuro!ath' gastro!aresis -,KOAR0, 0=8, bloating, diarr!ea, fecal incontinence ii. %#: gastric em!t'ing stud' for gastro aresis, ano7rectal manometr' studies for s !incter ressures iii. +ver't 'oman get steato!e atitis '= fibrosis, cirr!osis, &allorys !yaline (4ust like 2t+*) b. *y ot!yroidism consti ation, vs !y ert!yroidism !y erdefecation c. *y er arat!yroidism consti ation, !y ergastinemia (!ig! .a !ig! gastrin)

N. O.

A.

@. R. J. P.

Benal 3ailure a. Angiod's!lasia ,/ bleeding %rugs=)o#ins a. Ab# !seudomem*ranous colitis from CJ di"" b. 2ryt!romycin is motilin agonist gastroduodenal !y er eristalsis c. &g acts as la#ative d. )ons of !e atic= ancreatic drug reactions D mostly un redictable Autoimmune=immunologic a. :cleroderma motility dysf#n entire lengt! of ,/ tract due to collagen re lacing smoot! m b. :L2=BA=(olyarteritis nodosa i. /sc!emia to gallbladder acalculous cholec'stitis ii. /sc!emia to ancreas !ancreatitis c. (olymyositis=dermatomyositis oor bolus transfer in eso !agus (skeletal muscle) /nfections a. $IV candida=.&8=*:8 in eso !agus " &A8=)1 in small intestine .ancers a. Liver mets are very common (regnancy a. &,R</hemorrhoids due to increased abdominal ressure Aging a. (e tic ulcer disease ('= !eavy 0:A/% use), but usually ,/ ages 'ell

VA0C=LAR Q M,C$A)ICAL </O (stuff !e raised !is !and on is in bold) 1. +bstruction is either "unctional or mechanical a. &ec!anical barrier increased frequency s ike otentials as bo'el tries to clear com lete em yting of anyt!ing distal to obstruction " dilation=backu ro#imally c!anges in flora and t!en you t!ro' u your o'n oo 2. /f /&A ligated during aortic aneurysm surgery sigmoid colon deat!, t classically resents 'it! ost-o bloody diarr!ea &2.*A0/.AL +1:)BH.)/+0 .ancer, diverticula, stricture :#: dys !agia, regurgitation ,astric outlet obstruction ((H%, malignancy) :#: fullness, 0+0-billous ro4ectile vomiting Atresia (double bubble), annular ancreas, tumor :#: 1/LL+H: ro4ective vomiting Most common site o" o*struction Adhesions% tumors (luminal causes rare) :#: cram y ain, eit!er sim le=closed loo =strangulated )#: surgery, fluids (due to Nrd s ace losses) &alignancy, volvulus (LSB, due to la#ative abuse in 0*) :#: consti ation, distention, usually elderly 3H0.)/+0AL +1:)BH.)/+0

2so !agus :tomac! %uodenum :mall bo'el

(ost o erative %iabetic gastro aresis

/leus: anest!etic, inf#n, bo'el mani ulation, K abnormalities

Large 1o'el

+gilvieFs :yndrome, *irsc!s rung

%iverticulitis A endicitis )!rombus, emboli

(A)*+(*-:/+L+,%ue to erforated diverticula inflamm, bleeding .an be emergency but normally stays locally, !ealing '= strictures obstruction )# usually '= ab#, rarely surgery anymore e#ce t in regnancy 1o'el su lied by branc!es of celiac, :&A, and /&A, '!ic! anastomose e#tensively (resent '= ain out of ro ortion of !ysical findings (distension causes tenderness=guarding, not isc!emia) Hsually assoc '= !eart disease (recent &/ or a fib) ,m*olisF distal 0MA most commom% thus MCA is not *loc+ed and duodenum/transverse colon are s!ared Throm*usF earl' 0MA most common% so duodenum/transverse colon will *e necrotic , most common cause of mesenteric isc!emia, J<Q mortality

5$ARM 1. )reatment of * ylori-associated (H% a. )# only ts '!o test ositive for * ylori D em iric t!era y '=o confirmatory testing is not recommended (contradicts ot!er notes) b. Begiments s!ould include at least $ ab# " 1 anti-secretory agent i. 3irst line: tri!le thera!' o" ome!ra:ole (55I) > clarithrom'cin > amo#icillin ii. :econd line: quadru le t!era y of ome razole " bismut! " metronidazole " tetracycline 1. .an be first line if kno'n enicillin allergy or rior macrolide use Anti7secretor' agents %BH, &+A /0%/.A)/+0: :2 = .+0)BA/0%/.A)/+0: +me razole ((/, inhi*its active !roton !um!s 5=< (!art o" tri!le thera!') :2: ,/ related on !arietal cells &I *leed )o dose ad1 for renal=!e atic failure 1est acid su ression Anyt!ing due to e#cess acid %%/ '= * de endent drugs )ake '= food to stimulate um s 0o tolerance develo ment .imetidine *$ blockers, in!ibit *$ B on arietal 8ery similar to ((/s, less effective Must ad1 in renal !ts due to risk of Banitidine .0: disturbances cell less *.l roduction (gastrin > (otential for .-( interactions Ac! still 'ork t!o) (cimetidine which (7) CY5893) )olerance develo ment $. )reatment of ,2B% a. 0on- !arm al'ays D donFt eat before bed, reduce fat intake, avoid inciting foods, sto smoking, lost 't, slee at angle b. /f :# are intermittent, t# via lifestyle modification " OTC drugs like antacids=*$blockers

c. d.

/f :# are severe, t# via lifestyle modification " high dose 55I, 'it! maintenance t!era y %rugs include ((/, *$ blockers (bot! above), antacids, romotility agents &+A 0eutralize stomac! acid /0%/.A)/+0: Barely used b=c so many ot!er more effective drugs /0%/.A)/+0: &,R< )AK20 +33 &ABK2) :2 = .+0)BA/0%/.A)/+0: :2: ,/ related Accum of &g in renal dz :2 = .+0)BA/0%/.A)/+0: ,50 ContraF 5ar+inson/s !ts Caused arrh'thmias

%BH, antacids .a.+N &g+*$

%BH, &+A romitility agents (delayed gastric em tying ,2B%) Metoclo!ramide %o amine B antag " A-*) agonist */ Ac! smoot! m contraction .isa ride A*) stimulates myenteric le#us 2ryt!romycin 0timulate motilin R in smooth m gastric em tying via L2: N.

)reatment of ,/ bleeding a. 0on-variceal H,/ bleed: remove offending agent (usually 0:A/%), t# * ylori if resent, ((/ b. 8ariceal H,/ bleed: often life-t!reatening, requires !emodynamic stabilization iJ ;IR0T is "luid resuscitation (nl saline) and *lood re!lacement ii. 2ndosco y " sclerot!era y is t# of c!oice for actively bleeding varices b=c significant reduction in mortality iii. (revent musocal damage 1. * SO is target for revention of stress-related mucosal damage $. * S@ is target for revention of e tic-ulcer recurrence c. (!arm: octreotide=vaso ressin acutely, ((/ for revention Acute t# %BH, &+A /0%/.A)/+0: :2 = .+0)BA/0%/.A)/+0: +ctreotide 0omatostatin analog 'it! long 8ariceal bleeding :2: ,/ related, flus!ing, edema t1=$ contraction of vascular smoot! m reduction LIV,R Q 05LA)C$)IC *lood "low 8aso ressin (A%*) 8ariceal bleeding :2: arrh'thmias :timulates 81 B in eri ! vessels reduced blood flo' to varices :ucralfate /n acidic *, forms viscous gel t!at %ebatable, require lo' * to 'ork, :2: Al overload in renal ts referentially coats ulcers so giving '= ((/ may not !el O. ,astro aresis a. %elayed gastric em tying due to .0M damage (often %&) or smoot! m damage (scleroderma) b. )# '= romotility agents (ma4or ones listed above) i. .!olinergic agonists (bet!anec!ol) smoot! m stimulation, but ty ical :2 rofile (bradycardia, flus!ing, diarr!ea) ii. Ac!2/ (neostigmine) accum of Ac!, but above :2 " life-t!reatening bradycardia=A8 block iii. %o amine antags (dom eridone) loss of (-) on Ac!, but ty ical :2 rofile (dry mout!, ras!, dro'siness, abd ain) Hlcerative .olitis &+A Local anti-inflammatory via (-) (, " leukotriene synt!esis :ame /0%/.A)/+0: %+. for !roctitis/mild colitis Hsed in bot! acute=maintenance %+. for e#tensive/severe colitis Hsed in bot! acute=maintenance +ral: acute t# of e#tensive colitis Bectal: actue t# +0L/8: acute t# in systemic to#icity /f steroid-refractory=de endent :ame )V Iatc! :ulfa allergies 'it! sulfasalazine cannot be used alone :2: !y erglycemia, 0a=*$< retention adrenal insufficiency :2 = .+0)BA/0%/.A)/+0:

A.

%BH, anti-inflammatory &esalamine (rectal A-A:A) :ulfasalazine (oral A-A:A) .orticosteroids

Anti-inflamm " immunosu

ressant

immunomodulators Azat!io rine @-&erca to urine

Antagonize urine metabolism (-) %0A=B0A synt!esis :ame

:2: ancyto enia, must monitor '= .1. :2: liver necrosis " ancyto enia, must monitor '= .1., L3)s

@.

R.

J.

.ro!ns %isease a. &ore difficult to treat, more reliance on corticosteroids i. &ild-moderate: sulfasalazine (mesalamine if lesions in distal colon) ii. :evere: rednisone, budesonide iii. 3ulminant: /8 steroids /rritable bo'el syndrome a. &a4ority only require lifestyle modifications b. (!arm t# includes[ i. Antic!olinergics: usually as ad4unct '= some sedative, .+0)BA in glaucoma, myast!enia gravis, ,/ obstruction 1. *yoscyamine, atro ine, ro ant!eline, met!osco olamine, dicylomine ii. )y ical :2 rofile of dry mout!, consti ation, im aired motility 0ausea=8omiting &+A A-*) antagonist /0%/.A)/+0: .!emot!era y induced 0=8 :2 = .+0)BA/0%/.A)/+0:

%BH, +ndansetron

-setrons &etoclo romide %ro eridol A re itant

%o amine B antagonists :ubstance (=neurokinin B antag

.!emot!era y induced 0=8 .!emot!era y induced 0=8

%i !en!ydramine )rimet!obenzamide

*1 B blocker .entrally (-) c!emoB trigger zone

&otion sickness

:2: 2(: 3atal W) elongation (otent (OA< NOA (-) .+0)BA: cisa ride, terfenadine Iomen seek ot!er forms of +.( :2: dro'siness, dry mout!