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DISORDERS OF GALLBLADDER AND EXTRAHEPATIC BILIARY
TRACT
GALLBLADDER DISEASES
Cholelithiasis (Gallstones)
Gallstones trouble "p n zrirt"of adult populations.and are mainly of two types
I. Cholesterol stonetr.o*por.o of cryitalline cholesterol monohydrate (80%)
2. PigVtent stotrcs."*p"*a predominantly of bilirubin calcium salts (20%)
Pathogenesis and Risk Factors
o Bile is a maior fatn*uy for elimination of excess cholesterol from the body'
Cholesteror i, ,"iiJ"r"d water soluble through mixing with bile salts and lecithins
that are secreted into bile. When chJesterol concentrations exceed the
solubilizing ""p".i v or uit" (supersaturation), cholesterol deposited as solid
cholesterol crystals'
o cholesterol gallstone formation involves four concurrently occurring steps:
1. Supersaturation of the bile with cholesterol
z. Bstautist *eni of a nidus by microprecipitates of calcium salts
3. Hypomobility of the gallbladder (stasis), which promotes nidus formation
4. Mucus hypersecretion to trap the crystals and thus enhancing their
aggregation
. The presence of unconjttgated bilintbin in the biliary tree increases the
likelihood "ip;"t;;
stln! formation. This occurs in hemolytic anemias and
biliary tract inieJtions. The precipitates are insoluble calcium bilirubinate salts'
. The majority of individuals with gallstones (80%) have no identifying risk
fbctors
. Contributory risk factors include
t. Age anrT gertder: the incidence of gall stones increases with age in that only 5o/o
of the population yo,rngo than age +o"uut 25o/o of those older than 80 years develop
stones. The prevaience in women is about twice as high as in men'
2. Ethnic ora g"ogiphic'. gallstones are more prevalent in Western industrialized
societies and uncommon in developing ones'
3. Heredity; family history in1pu.B inJteased risk, as do a variety of inborn errors of
rnetabolismrrr.fturthoseassociatedwithimpairedbilesaltsynthesisandsecretion'
4. Environment: estrogenic influ.nces, including oral contraceptives and
pregnancy, in"r"ur"-tepltic cholesterol uptake and synthesis, leading to excess
6;UutY secretion of cholesterol'
5. obesity, ,op,a ,,nighr loss, and| reatntent with lhe hypocholes|.erolemic agent
cloJibrateare itrongly associated with increased biliary cholesterol secretion'
6.Ggtlbtadderhypomotititypredisposesto.gallstones.Itisassociatedwith
pregnancy, ,ujia ir'"ight loss, una rpinur cord injury. In most cases, however, the
i.,yp"o*otitlty is present without obvious cause'
Pathologic .features
pure cholesterol stones always formed within the gall bladder as pale to tan
yellow, und u" ouoid ancl finn. ThLv mav be single Uut mo1 111:1:":,'"tple
In
the latter instance, they assum. u f*ttti surface from apposition to one another'
Most cholesterol stones are radiolucent, bur 20%of them ntay have sufJicient
calcittm carbonste to t'ender thenr radiopaqrrc'
pigment stones-n,ay arise anywhere in int Uitiuty tree (gall bladder' intra- or extra-
hepaticureau.tsiundu,.-:.i,1*blacktlt.hrown.Ingeneral,blackpigmentStones
are found in sterile bile, while brown stones are found in infected bile' Black stones
areusuallysmall,presentinlargenumbers,andcrunlbleeasilyBrownStonestend

to be single or few in number. Because of the incorporation of calcium carbonates

and phosph ates, 5a% i, vin of btack stures or, ,odiopoque- Brown stones, which
corftnin ialcitm soaps, are radioluc,errt'
Gallstones u.. urr#oi;;1;;; isolo ot the cases Pain is the principal svmptom
and it tends to be Severe, either constant or "colicky" from an obstructed gallbladder
orwhensmallgallstonesmovedown-streamandlodgeinthe-b']i11.,".
Inflammation ortir"-g;llbladder" in association with stones' also generates paln'
Connplications of gall stones include
1. EmPYema
2. Perforation
3. Fistulae
L Cholongitis
5. O bstrttcti ve chol esta'si's
ir::tr:'::It.ur stones that are dangerous; the larger the carculi, the less likelv
they are to enter the cystic or commo*iucts to produ-e obstruction' Occasionally a
large stone ,,'uV *0" directly inlo an aJ;u,"nt loop of small bowel' generating
i*Euinuf obstruction (" gallstone ileus")'
Fffitilillt:tacute, chronic, or acute superimposed on chronic, and armost always
occurs in associati"" -iir, gallstones. Its'epidemiologic distribution closely parallels
that of gallstones.
Gross features
Acute cholecYstitis
. The gallbladder is usually enlarged, tense, and bright red or blotchy' violaceous
to green-blu"t Air.oioration. The latter is due to subserosal hemorrhages'
e .lhc serosal covering is tiequently covere'cl try fibrirr or suppurative exuclate'
oIn90ohofcasesstoneSarepresent,oftenobstructingthecysticduct.
o The gallbladder lumen is fittert with cloudy or turbid bile (contain fibrin' blood'
andfrankpus),Whentheexudateisp.,,.pu',theconditionisreferredtoas
em1Yema of the gullbladdet
o In milcl cases;J;llbladder wall is thickened, edematous, and hyperemic'
olnmoreseverecasesthegallbladderistransformedintoagreeu-blackrrecr.otic
orgun, termed gangrenous cholecy stitis'
Microscopical features r: .L ^ -. ^-. ^ r ^^+f a
o The inflammatory reactlons conslst of the usual patterns of acute inflammation
(i.e., edema, "Lr?opniric
infiltratio",.""r.::lT llll-.^tjb":
tll1L^b" suppurative
wittrtrantabscessformation'orevenfuatesingangrenousnecrosls.
Acute Crilculous Cholecystitis refers to acute inflammation of a gallbladder that
contains stones and is precipitated by obstruction^of the gallbladder neck or cystic
duct. 1r is the ntost common maJor cimplication of gallstones and the most con?mon
reason for em ergency cho I ecystectomy'
lnitially it is the ..rult of chemical irritation and inflammation of the gallbladder
wall in the setting of obstruction to bile outflow'
A cute N o n- Calcul o us Ch ol ecy stitis
Uptol0%ofguttutudo.,sremovedforacutecholecystitiscontainnogallstones.
Mostof these cases occur in sertously ill patients e'g' after severetrauma such as a
major surgery, *oa, vehicle accidenis, severe burns as well as sepsis. In such cases
mally events are thought to contribute to this condition such dehydration'

gallbladder stasis and sludging, vascular compromise, and, ultimately' bacterial

contamination'
chronic cholecystitis may be the sequel to repeated PTt of acute cholecystitis'
but in most instanr"s it develops de novo' Like acute cholecystitis it is almost
ulways associated*in'ii3ronisbutthese do not seem to have a direct role in the
initiation of inflammurion. Rather, supersaturati:i^ ""lltt
predisposes to both
chronic inflammation and, in most initances, stone formation Microorganisms'
usually E. coli anO enterotorri, can be cultured from the bile in only about one-
third ofcases.
Pathologicalfeutures
o The changes are extremely variable and sometimes minimal'
oThemerepresenceofstoneswithinthegallblacld.:,.Y.nintheabsenceofacute
inflammation, i, onr";.k.; as suffrcienijustification for the diagnosis'
oThegallbladder--uvu"contracted'ofnormalsize,orenlarged.
oThemuscularlayerandsubserosaareoftenthickenedfromtrbrosis.
olntheabsenceofsuperimposedacutecholecystitis,murallymphocytesarethe
onlY t'eature of inflammation'
DISORDERS OF EXTRAIIEPATIC BILE DUCTS
Choledocholithiasisandcrrorangitisare.'.frlyentlvSeentogether'
Choledocholitltiasis is the p."r.n"".oF stones within the biliary tree' Almost all
these stone, u," ooi.,.a ao* the gallbladder. Symptoms are absent in loo/o of the
cases, but when ;;r; they are au. to biliary
-obstruction or its sequele such as
pancreatitis, "hotffi,ir,'i.p^tl.
abscess, secondary biliary cirrhosis' or acute
calculous cholecystttts' of the wall of bile ducts.
Clroti"gids refers to acute mostlv bacterial inflammatt"", "1i"""i1?in:ilffii
Most cases are a*-i" "Ustruition
bile flow, mostly by choledocholithiasts'
However, ,,rrgi"uilironr*olon of the biliary tree is also a recognized cause'
Uncommon causes include tumors, indweiling .':t':.' or catheters, acute
pancreatitis,andbenignstrictures.Bacteriamostlikelyenterthebiliarytract
ihrough the sphinct.i Ir oaoi, rather than by the hem.atogenous route' Ascending
cholangitisr.i.r, io it" tendency of tu"tttiu' once within the biliary tree' to infect
intrahepatic bih;;;;r. rl" urua putnogens are E..c!li, Klebsiella, clostridium'
Bacteroider, "r"'.'ii7rritl,
irroa (puin, jaundice and fever) is the most common
mode of Presentation'
The most ,"u.." ior. of cholangi tis is suppurative. cho,langrlls, in which purulent
bile fills and disteriir-tii. auor, iuittt an atiendant risk of liver abscess formation'
Secondary BiliarY Cirrhosis
Prolongedoustructlonoftheextrahepaticbiliarytreeresultsinsecondarybiliary
cirrhosis.
Couses inclutle
1 Exfi'ahepattc cholelithiasis(the most common cause)
2. Malignancies of thebiliary tree and head of the pancreas
3. striclures resulting from previous surgical procedures
tf""'::l;:rn'J'Jrp^oiogi" features of cholestasis are entiretv reversible with
conection "f ,frJ'"Urt-*.tion. Howev:r,-,r..ond1ry inflammation resulting lrom
biliaryobstructioninitiatesperiportalfibrogenesis,whicheventuallyleadsto

scarring and nodule formation, generating secondary biliary cirrhosis. Subtotal

obstrttction may promote ascending cholangitis, which further contributes to the
damage. Enteric organisms such as coliforms and enterococci are common
offenders.
Bitiary Atresia is a major cause of neonatal cholestasis (30%). Biliary atresia is
defined as a complete obstruction of bile.flow caused by destruction or absence of
all or part of the ertruhepatic bile ducts. It is the most frequent cause of death
from liver disease in early childhood. The salient-feah*'es qf biliary atresia include
1. Inflammatoryfibro,sirtg stricture of exfi'ahepatic biliary tree (hepatic or common
bile ducts)
2- Inflammalory destruction of the major intrahepatic bile ducts
3. Features of biliary obstruction on liver biopsy
4. Periportal fibrosis and cinhosis tvithin 3 to 6 months of birth
Laboratory findings do not distinguish befiveen biliary atresia and intrahepatic
cholestasis, but a liver biopsy provides evidence of bile duct obstruction in 90% of
cases of bilicny atresia. Without surgical intervention, death usually occurs within 2
years of birth.
TUMORS
Carcinoma of the Gallbladder is the most frequent malignant tumor of the biliary
tract. It occurs most frequently in the age group 60-70 years. The mean 5-year
survival is 5%a because it is rarely discovered at a resectable stage. Gallstones are
present in about 75Yo of the cases. Presumably, gallbladders containing stones or
infectious agents develop cancer as a result of recurrent trauma and chronic
inflammation. The presence of abnormal choledocho-pancreatic duct junction is
considered to be a risk factor.
Gross features
o The cancer is either exophytic ffungating) or infiltrative growth.
o The infiltrative pattern, which is the more common, usually appears as a poorly-
defined area of thickening and induration of part or whole of gall bladder wall.
o The exophytic pattern grows into the lumen as cauliflower mass, but at the same
time it invades the underlying wall .
Microscopic features
c Well- to poorly4ffirentiated infiltrative adenocarcinomas that is sometimes
papillary.
By the time gallbladder cancers are discovered, most have invaded the liver directly
and many have extended to the cystic duct and adjacent bile ducts and lymph nodes
at the portahepatis.
Preoperative diagnosis of gall bladder carcinoma is seen in only a20o/o of the cases.
The fortunate person develops early obstruction and acute cholecystitis befbre
extension of the tumor into adjacent structures or undergoes cholecystectomy for
coexistent symptomatic gallstones. Preoperative diagnosis rests largely on detection
of gallstones along with abnormalities in the gallbladder wall documented by
imaging studies.
Cholangiocarcinomas are adenocarcinomas arising from cholangiocytes
(epithelial cells lining) in bile ducts within and outside of the liver. Extrahepatic
cholangiocarcinoma.s (2/3 of the cases) may develop at the hilum (Klat.skin tumors)
or more distally in the biliary tree, down to the peripancreatic portion of the distal
common bile duct- Thev occur mostly in individuals 50 to 70 vears of ase. The

prognosis of cholangiocarcinomas is poor because they

unti tut.. and most patients have unresectable tumors'
Risk factors include
t. Pi'imary sclerosing cholangiti's
2. Fibrocystic diseases of the biliary tree
3. Exposure rc fniritrasl (which is no longer used in radiography of the biliary
tree).
Prfih olo gi c nl .fe ature s
. Due to early development of obstructive jaundice, these tumors are detected as
small firm, gruf nia.rles within the biie duct wall. Alternatively, they are
diffusely infiltraiive lesions that create thickening of the wall.
oTheseadenocarcinomasaregenerallywell-differentiatedwithanabundant
fibrous stroma
o Cholangiocarcinomas may spread to extrahepatic sites such as regional lymph
nodes, lungs, & bones'
Mean survival time is around 12 months'
are generallY asYmPtomatic


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