FJY SGD 27: GI 3 Liver and Gallbladder 1. A 45 year old woman was admitted due to colicky RUQ pain.

On PE: obese wit icteric sclerae. !orkup re"ealed t e presence o# stone in common bile duct. Pertinent laboratories were normal e$cept #or ele"ated c olesterol. E$plain t e p ysiolo%ical mec anisms in"ol"ed in:

&allstones
- A %allstone is a crystalline concretion formed it!in t!e "allbladder by accretion of bile com#onents$ %!ese calc&li are formed in t!e "allbladder b&t may distally #ass into ot!er #arts of t!e biliary tract s&c! as t!e cystic d&ct' common bile d&ct' #ancreatic d&ct or t!e am#&lla of (ater$ - )resence of "allstones in t!e "allbladder may lead to ac&te c!olecystitis' an inflammatory condition c!aracteri*ed by retention of bile in t!e "allbladder$ )resence of "allstones in ot!er #arts of t!e biliary tract can ca&se obstr&ction of t!e bile d&cts' !ic! can lead to serio&s conditions s&c! as ascendin" c!olan"itis or #ancreatitis$ - +!olesterol "allstones develo# !en bile contains too m&c! c!olesterol and not eno&"! bile salts$ ,esides a !i"! concentration of c!olesterol' t o ot!er factors are im#ortant in ca&sin" "allstones$ %!e first is !o often and !o ell t!e "allbladder contracts- incom#lete and infre.&ent em#tyin" of t!e "allbladder may ca&se t!e bile to become overconcentrated and contrib&te to "allstone formation$ %!is can be ca&sed by !i"! resistance to t!e flo of bile o&t of t!e "allbladder d&e to t!e com#licated internal "eometry of t!e cystic d&ct$%!e second factor is t!e #resence of #roteins in t!e liver and bile t!at eit!er #romote or in!ibit c!olesterol crystalli*ation into "allstones$ In addition' increased levels of t!e !ormone estro"en' as a res&lt of #re"nancy or !ormone t!era#y' or t!e &se of combined /estro"en-containin"0 forms of !ormonal contrace#tion' may increase c!olesterol levels in bile and also decrease "allbladder movement' res&ltin" in "allstone formation$

'olicky RUQ Pain

- ' olecystitis is inflammation of t!e "allbladder' !ic! occ&rs most commonly d&e to obstr&ction of t!e cystic d&ct it! "allstones /c!olelit!iasis0$ ,loc1a"e of t!e cystic d&ct it! "allstones ca&ses acc&m&lation of bile in t!e "allbladder and increased #ress&re it!in t!e "allbladder$ +oncentrated bile' #ress&re' and sometimes bacterial infection irritate and dama"e t!e "allbladder all' ca&sin" inflammation and s ellin" of t!e "allbladder$ Inflammation and s ellin" of t!e "allbladder can red&ce normal blood flo to areas of t!e "allbladder' !ic! can lead to cell deat! d&e to ins&fficient o2y"en$ - +!olecystitis &s&ally #resents as a #ain in t!e ri"!t &##er .&adrant or e#i"astric re"ion$ %!e "allbladder may be tender and distended$ Sym#tomatically it differs from biliary colic by t!e #resence of an inflammatory com#onent /fever' increased !ite cell co&nt0$ 3ore severe sym#toms incl&de !i"! fever' s!oc1 or 4a&ndice !ic! indicate t!e develo#ment of com#lications s&c! as abscess formation$ - %!e ma4ority of cases of c!olecystitis are ca&sed by "allstones im#actin" or im#in"in" on t!e flo of bile in t!e biliary tree$ Gallstone im#action' called c!olelit!iasis' most commonly occ&rs at t!e nec1 of t!e "allbladder or in t!e cystic d&ct$ %!is leads to ins#issation /t!ic1enin"0 of bile' bile stasis' and secondary infection by "&t or"anisms' #redominantly E. Coli and Bacteroides s#ecies$%!e "allbladder5s all becomes inflamed$ 62treme cases may res&lt in necrosis and r&#t&re$ Inflammation often s#reads to its o&ter coverin"' t!&s irritatin" s&rro&ndin" str&ct&res s&c! as t!e

dia#!ra"m and bo el$

(cteric )clerae
- Also 1no n as 4a&ndice !ic! is a yello is! #i"ment of t!e s1in' t!e con4&nctival membrane aro&nd t!e sclera and ot!er m&co&s membranes ca&sed by !y#erbilir&binemia$ %!is !y#erbilir&binemia s&bse.&ently ca&ses increased levels of bilir&bin in t!ee2tracell&lar fl&id$ +oncentration of bilir&bin in blood #lasma is normally belo 7$2 m"8dL /92:;mol8L0$ A concentration !i"!er t!an 2$: m"8dL /<:=;mol8L0 leads to 4a&ndice$ Ja&ndice is often seen in liver disease s&c! as !e#atitis or liver cancer$ It may also indicate le#tos#irosis or obstr&ction of t!e biliary tract' for e2am#le by "allstones or #ancreatic cancer' or less commonly be con"enital in ori"in /e$"$' biliary atresia0$ - 3a4ority of bilir&bin comes from t!e brea1do n of !eme from e2#ired red blood cells$ %!e !emo"lobin in red blood cells is #!a"ocytosed by macro#!a"es' and s#lit into its !eme and "lobin #ortions$ % o reactions t!en ta1e #lace it! t!e !eme molec&le$ %!e first o2idation reaction is cataly*ed by t!e en*yme !eme o2y"enase and res&lts in biliverdin /"reen color #i"ment0' iron and carbon mono2ide$ %!e ne2t ste# is t!e red&ction of biliverdin to a yello color tetra#yrol #i"ment called bilir&bin by en*yme biliverdin red&ctase >ncon4&"ated bilir&bin travels to t!e liver to be con4&"ated it! "l&c&ronic acid to become more ater sol&ble$ %!is con4&"ated bilir&bin is e2creted from t!e liver into t!e biliary and cystic d&cts as #art of bile$ - Since t!ere is obstr&ction of t!e biliary tract' bilir&bin is not converted into e2cretable materials !ic! res&lts to a b&ild-&# of bilir&bin in t!e body !ic! leads to 4a&ndice and icteric sclerae$ *. +escribe t e bile acid recyclin% by t e entero epatic circulation 6ntero!e#atic circ&lation refers to t!e circ&lation of biliary acids' bilir&bin' dr&"s' or ot!er s&bstances from t!e liver to t!e bile' follo ed by entry into t!e small intestine' absor#tion by t!e enterocyte and trans#ort bac1 to t!e liver$ ?e#atocytes metaboli*e c!olesterol to c!olic acid and c!enodeo2yc!olic acid$ %!ese li#id-sol&ble bile acids are con4&"ated mainly to "lycine or ta&rine molec&les to form atersol&ble #rimary con4&"ated bile acids$ %!ese bile acids travel to t!e "all bladder d&rin" t!e interdi"estive #!ase for stora"e and to t!e descendin" #art of t!e d&oden&m via t!e common bile d&ct t!ro&"! t!e ma4or d&odenal #a#illa d&rin" di"estion$ @:A of t!e bile acids !ic! are delivered to t!e d&oden&m ill be recycled by t!e entero!e#atic circ&lation$ D&e to t!e #? of t!e small intestine' most of t!e bile acids are ioni*ed and mostly occ&r as t!eir sodi&m salts !ic! are t!en called B#rimary con4&"ated bile salts$C In t!e lo er small intestine and colon' bacteria de!ydro2ylate some of t!e #rimary bile salts to form secondary con4&"ated bile salts / !ic! are still ater sol&ble0$ Alon" t!e #ro2imal and distal ile&m' t!ese con4&"ated #rimary bile salts are reabsorbed actively into !e#atic #ortal circ&lation$ ,acteria decon4&"ate some of t!e #rimary and secondary con4&"ated bile salts bac1 to li#id sol&ble bile acids' !ic! are #assively absorbed into !e#atic #ortal circ&lation$ Finally' t!e con4&"ated bile acids !ic! remained &nioni*ed con4&"ated bile acids are #assively absorbed$ (eno&s blood from t!e ile&m "oes strai"!t into t!e #ortal vein and t!en into t!e liver sin&soids$ %!ere' !e#atocytes e2tract bile acids very efficiently' and little esca#es t!e !ealt!y liver into systemic circ&lation$ %!e net effect of entero!e#atic recirc&lation is t!at eac! bile salt molec&le is re&sed abo&t 2= times' often m&lti#le times d&rin" a sin"le di"estive #!ase$

,. A 5- year old laborer was admitted due to &( bleedin% and altered sensorium. Personal istory re"ealed t at e is an alco olic be"era%e drinker #or 15 years. .e drinks 4 bottles o# beer or */, bottle o# %in e"ery ni% t. PE: pale0 distended abdomen. Rectal e$amination s owed black stools on e$aminin% #in%er. A dia%nosis o# li"er cirr osis was %i"en. Elaborate t e p ysiolo%ical mec anisms in e patient i# e is #ound to a"e: 1 .ypo%lycemic attacks 1 2leedin% tendencies 1 Enlar%in% abdomens 1 3ental alterations 'irr osis is a res&lt of advanced liver disease$ It is c!aracteri*ed by re#lacement of liver tiss&e by fibrosis /scar tiss&e0 and re"enerative nod&les /l&m#s t!at occ&r d&e to attem#ted re#air of dama"ed tiss&e0$ %!ese c!an"es lead to loss of liver f&nction$ +irr!osis is most commonly ca&sed by alco!olism' !e#atitis , and !e#atitis +' and fatty liver disease' b&t !as many ot!er #ossible ca&ses$ Some cases are idio#at!ic /of &n1no n ca&se0$

.ypo%lycemic attacks
- Sometimes called !e#atic diabetes$ - %!e !e#atocyte actively stores "l&cose by convertin" it to t!e lon"c!ain starc!' "lyco"en$ Glyco"en can t!en be later bro1en do n to release "l&cose into t!e "eneral circ&lation$ - %!e im#airment of t!is mec!anism can lead to more serio&s manifestations of liver !y#er"lycemia or !y#o"lycemia$ - )atients it! severe liver disease often !ave "l&cose tolerance c&rves very m&c! li1e t!ose seen in diabetes mellit&s$ As dietary inta1e is decreased or absent' t!e !e#atocytes are not ell able to mobili*e "l&cose from !at little stored "lyco"en t!ere is' and so t!ese #atients !ave e#isodes of !y#o"lycemia$

2leedin% tendencies
- In t!e cirr!otic liver' t!e scar tiss&e bloc1s t!e flo of blood ret&rnin" to t!e !eart from t!e intestines and raises t!e #ress&re in t!e #ortal vein /#ortal !y#ertension0$ D!en #ress&re in t!e #ortal vein becomes !i"! eno&"!' it ca&ses blood to flo aro&nd t!e liver t!ro&"! veins it! lo er #ress&re to reac! t!e !eart$ %!e most common veins t!ro&"! !ic! blood by#asses t!e liver are t!e veins linin" t!e lo er #art of t!e eso#!a"&s and t!e &##er #art of t!e stomac!$ - As a res&lt of t!e increased flo of blood and t!e res&ltin" increase in #ress&re' t!e veins in t!e lo er eso#!a"&s and &##er stomac! e2#and and t!en are referred to as eso#!a"eal and "astric varices- t!e !i"!er t!e #ortal #ress&re' t!e lar"er t!e varices and t!e more li1ely a #atient is to bleed from t!e varices into t!e eso#!a"&s or stomac!$ - ,leedin" from varices &s&ally is severe and' it!o&t immediate treatment' can be fatal$ Sym#toms of bleedin" from varices incl&de vomitin" blood /t!e vomit&s can be red blood mi2ed it! clots or Ecoffee "ro&ndsE in a##earance' t!e latter d&e to t!e effect of acid on t!e blood0' #assin" stool t!at is blac1 and tarry d&e to c!an"es in t!e blood as it #asses t!ro&"! t!e intestine /melena0' and ort!ostatic di**iness or faintin" /ca&sed by a dro# in blood #ress&re es#ecially !en standin" &# from a lyin" #osition0$

- ,leedin" also may occ&r from varices t!at form else !ere in t!e intestines' for e2am#le' t!e colon' b&t t!is is rare$ For reasons yet &n1no n' #atients !os#itali*ed beca&se of actively bleedin" eso#!a"eal varices !ave a !i"! ris1 of develo#in" s#ontaneo&s bacterial #eritonitis$

Enlar%in% abdomens
- )rimarily ca&sed by ascites' or acc&m&lation of fl&id$ - As cirr!osis of t!e liver becomes severe' si"nals are sent to t!e 1idneys to retain salt and ater in t!e body$ %!e e2cess salt and ater first acc&m&lates in t!e tiss&e beneat! t!e s1in of t!e an1les and le"s beca&se of t!e effect of "ravity !en standin" or sittin"$ %!is acc&m&lation of fl&id is called edema or #ittin" edema$ /)ittin" edema refers to t!e fact t!at #ressin" a fin"erti# firmly a"ainst an an1le or le" it! edema ca&ses an indentation in t!e s1in t!at #ersists for some time after release of t!e #ress&re$ Act&ally' any ty#e of #ress&re' s&c! as from t!e elastic band of a soc1' may be eno&"! to ca&se #ittin"$0 %!e s ellin" often is orse at t!e end of a day after standin" or sittin" and may lessen overni"!t as a res&lt of t!e loss of t!e effects of "ravity !en lyin" do n$ As cirr!osis orsens and more salt and ater are retained' fl&id also may acc&m&late in t!e abdominal cavity bet een t!e abdominal all and t!e abdominal or"ans$ %!is acc&m&lation of fl&id /called ascites0 ca&ses s ellin" of t!e abdomen' abdominal discomfort' and increased ei"!t$

3ental alteration
- D!en cirr!osis is #resent' liver cells cannot f&nction normally eit!er beca&se t!ey are dama"ed or

beca&se t!ey !ave lost t!eir normal relations!i# it! t!e blood$ In addition' some of t!e blood in t!e #ortal vein by#asses t!e liver t!ro&"! ot!er veins$ %!e res&lt of t!ese abnormalities is t!at to2ic s&bstances cannot be removed by t!e liver cells' and' instead' t!e to2ic s&bstances acc&m&late in t!e blood$ - D!en t!e to2ic s&bstances acc&m&late s&fficiently in t!e blood' t!e f&nction of t!e brain is im#aired' a condition called !e#atic ence#!alo#at!y$ Slee#in" d&rin" t!e day rat!er t!an at ni"!t /reversal of t!e normal slee# #attern0 is amon" t!e earliest sym#toms of !e#atic ence#!alo#at!y$ Ft!er sym#toms incl&de irritability' inability to concentrate or #erform calc&lations' loss of memory' conf&sion' or de#ressed levels of conscio&sness$ >ltimately' severe !e#atic ence#!alo#at!y ca&ses coma and deat!$ - %!e to2ic s&bstances also ma1e t!e brains of #atients it! cirr!osis very sensitive to dr&"s t!at are normally filtered and deto2ified by t!e liver$ Doses of many dr&"s t!at normally are deto2ified by t!e liver !ave to be red&ced to avoid a to2ic b&ild&# in cirr!osis' #artic&larly sedatives and dr&"s t!at are &sed to #romote slee#$ Alternatively' dr&"s may be &sed t!at do not need to be deto2ified or eliminated from t!e body by t!e liver' for e2am#le' dr&"s t!at are eliminated by t!e 1idneys$