3.

09 Diseases of the Gallbladder and Biliary Tree

Dr. Luis G. Salvador | November 26, 2018

I. GALLBLADDER & BILIARY TREE DISEASES • Other sources: hepatic turnover of heme or hemoproteins,
premature destruction of RBC precursors in bone marrow
A. Introduction • Intracellular heme oxygenase oxidizes heme to biliverdin,
B. Gallstones/Cholelithiasis immediately reduced to bilirubin by biliverdin reductase
C. Biliary Pain
D. Acute Cholecystitis • Albumin in the blood transports bilirubin to the liver where it is
E. Mirizzi’s Syndrome taken up by hepatocytes via facilitated diffusion and is
F. Choledocholithiasis conjugated with glucoronic acids via UDP-glucorynyl
G.Cholangitis transferase (uridine phosphate)
H. Acalculous Cholecystitis
I. Emphysematous Cholecystitis • Bilirubin glucuronide or conjugated bilirubin: water soluble,
J. Complications of Cholecystitis non-toxic. Excreted to the bile canaliculi via the MRP2
K. Cholecystoenteric Fistula transporter, small amount is released in the plasma, measured
L. Porcelain Gallbladder as direct bilirubin. Can be detected in urine using routine
M.Postcholecystectomy Complications
dipstick test.
N. Postcholecystectomy Syndromes
O.Hyperplastic Cholecystoses • Within the intestine gut lumen, most bilirubin glucuronides are
P. Primary Sclerosing Cholangitis deconjugated by bacterial beta-glucuronidases, forming
Q.Congenital Anomalies urobilinogen, further metabolized into stercobilinogen and be
R. Choledocal Cyst
oxidized and excreted in the stool as stercobilin (gives stool
S. Cholangiocarcinoma]
T. Gallbladder Carcinoma brown color)

II. REFERENCES

Legend:
Supplementary Emphasized
Audio Recording
Book Information Notes
& U G

I. GALLBLADDER & BILIARY TREE DISEASES

A. Introduction
1. Bilirubin Metabolism and Production

Figure 2. Bilirubin metabolism and production

• Urobilinogen
o Some are reabsorbed from the gut and reenters the portal
circulation, then goes back to the liver to be recycled
o A remainder is filtered by the kidneys, oxidized to
urobilin (colors the urine yellow)
Figure 1. Bilirubin metabolism and production
§ measured as urine urobilinogen through
routine dipstick
• Bilirubin is a potentially toxic catabolic product of heme
§ Not detected in urine = severe biliary obstruction
metabolism.
• Majority of heme are derived from the breakdown of senescent or
abnormal RBCs by the reticuloendothelial system (RAS)
(macrophage, spleen, liver, bone marrow)

Cruz D., Cruz W., Cupino, Custodio EDITOR Bihag 09267108501 of
TRANSCRIBERS 1 18
 2. Bile o Chenodeoxycholic acid (drug now used for
• What stimulates the secretion of bile? Fat. Once you have take in (CDCA) dissolution of stones)
fat and it reaches the stomach, it will stimulate the secretion of CCK
(cholecystokinin)
o CCK is responsible for the contraction of the GB to release 4. Regulation of Bile Flow
bile into biliary tree to the ampulla and into the duodenum. • Active transport of bile acids from hepatocytes into bile canaliculi
• Notice the symptomatologies related to these are all related to the • Active transport of other organic anions
digestion of food. History is related to food intake. • Cholangiocellular secretion
• Gallbladder is a storage organ for bile. Bile is not produced here but o Secretin mediated and cAMP dependent
is concentrated here. o Secretion of Na and HCO3 rich fluid in the bile ducts
o Most important mechanism among the 3
Table 1. Hepatic vs Gallbladder bile
Hepatic Bile Gallbladder Bile
• Isotonic • Less Cl and HCO3 QUICK RECALL:
• 3-4 g/dl solute • 10-15 g/dL solute concentration
Bile is formed in the hepatic lobules -> secreted into the
concentration • 30 cc (max amount of bile in GB)
canaliculi -> drains into ductule and intrahepatic bile ducts -> left
• Basal secretion – 500 to • Concentrated within the and right hepatic ducts -> common hepatic duct -> stored and
600 cc gallbladder by energy-dependent concentrated in the gallbladder -> released from gallbladder via
• Concentrated within the transmucosal absorption of water cystic duct -> common bile duct
gallbladder and electrolytes
• Almost entire bile acid pool may be 5. Diseases of the Gallbladder
sequestered in the GB on • Congenital Anomalies
overnight fast o Mostly asymptomatic, incidental finding on ultrasound
(screening tool or manifestations of gallstones)
§ Agenesis
• Major solute components of bile:
§ Duplication
o Bile acids – approximately 80%
§ Diverticula
o Lecithin and other phospholipids – 16%
§ Phrygian cap
o Unsterified cholesterol – 4%
§ Minimum amount of cholesterol • Partial or complete septum separates body of
§ If percentages differ on all 3, formation of stones may gallbladder from the fundus. Found incidentally on
occur ultrasound.
§ Lithogenic bile when unesterified cholesterol reaches 8 • Gallstones, number one problem
– 10% o Cholesterol stones/ bile sludge
o Pigment stones
3. Bile Acids
B. GALLSTONES (CHOLELITHIASIS)
• Notice the symptomatologies related to these are all related to the
1. Generalities
digestion of food. History is related to food intake
• Gallbladder is a storage organ for bile. Bile is not produced here but • More common in females 3 Fs (female, fat and forty)
is concentrated here. • Formed because of abnormal bile composition
• Bile acids facilitates biliary excretion of cholesterol, the normal o Supersaturation of bile with cholesterol
intestinal absorption of of dietary fats mainly cholesterol and fat o Decreased in lecithin
soluble vitamins via micellar transport mechanisms. o hypomotility of gallbladder
• Solubility of cholesterol in bile dependent on total lipid concentration • Often found incidentally during abdominal ultrasound
and the relative molar percentages of bile acids and lecithin. o >95% sensitivity for cholesterol stones >/- 1.5mm
• Norm al ratios favor formation of solubilizing mixed micelles while • 75% to 80% remain asymptomatic
abnormal ratios promote precipitation of cholesterol crystals in bile • Probability of developing symptoms within 5 yrs after diagnosis is
via an intermediate liquid crystal phase. 2-4% and decreases thereafter to 1-2%
• Bile acids also serve as a major physiologic force for hepatic blood • Yearly incidence of complications is 0.1 to 0.3%
flow and aid in water and electrolyte transport in the small intestines • Those remaining asymptomatic for 15 yrs were unlikely to develop
and colon. symptoms during follow-up
Table 2. Types of Bile Acids • Those who develop complications experience prior warning
Primary Secondary sympotms
• Synthesized from liver, • Formed in the colon as • Cumulative risks of death due to GB disease on expectant
conjugated with glycine or bacterial metabolite action on management is small
taurine and secreted into bile primary bile acids • Belching, bloatedness, fullness or upper abdominal
• No cholesterol consumption = o Deoxycholate
discomfort especially after eating heavy meals can be attributed
less bile acids; bile acids are o Lithocholate
needed to digest fat to gallstones if other diagnoses have been ruled out
o Ursodeoxycholic acid
o Cholic acid • Prophylactic cholecystectomy NOT warranted
– stereoisomer of CDCA

3.09 Biliary Diseases 2 of 18
 § Family History: Hypercholesterolimic syndromes

o Dietary Risk Factors

§ Overnutrition or malnutrition
§ High calorie
§ Low fiber
§ High refined carbohydrates

o Lifestyle Risk Factors

§ Low grade activity
§ Prolonged fasting
§ Rapid weight loss
§ Mobilization of tissue cholesterol leads to increased
biliary secretion with decreased entero-hepatic
circulation of bile acids
§ Weight cycling (weight loss-gain-loss-gain)
§ Oral contraceptives or Estrogen replacement therapy

o Associated Conditions
§ Obesity and Metabolic syndrome
§ Normal bile acid pool and secretion, increased
Figure 3. Cholelithiasis. Gallstones forms in the gallbladder and secretion of cholesterol
could lodge in the cystic duct or common bile duct. § Gallbladder hypomotility – leads to stasis and sludge
§ Prolonged TPN, fasting, pregnancy, drugs such as
Octreotide
2.Types of Gallstones
§ Pregnancy and parity
§ Impaired gallbladder emptying caused by
Table 3. Types of Gall Stones progesterone which inhibits smooth muscle
Cholesterol Stones Pigment Stones contractility and impairs emptying
• 80% frequency (more • 20% frequency § Plus the influence of estrogen
common) • Calcium bilirubinate § Clofibrate therapy- increase biliary secretion of
cholesterol
• >50%: cholesterol • <20% cholesterol composition
monohydrate composition • Black
• With calcium salts, bile • Brown: if secondary to chronic • PATHOGENESIS
pigments, proteins, and fatty biliary infection o Cholesterol: insoluble in water needs solubilizing lipids (bile
acids • Softer stones thus easier to acids and phospholipids) for its incorporation into bile. Inability
• Accounts for >90% of break to incorporate in water leads to crystallization.
gallstones in Western • Asian countries § Bile lipid secretion is regulated by ATP binding
countries cassette (ABC) transporters in hepatocyte canalicular
• Harder stones membrane
§ Bile salt export pump (BSEP) ABCB11 transports bile
acids into bile
§ Multi-drug resistance p-glycoprotein 3 (MDR3)
ABCB4 translocates phosphatidylcholine from the inner
to the outer leaflet of the canalicular membrane
§ Transporter ABCG5/G8 secretes cholesterol into bile
§ Cholesterol and phosphatidylcholine reach the bile as
unilamellar vesicles converted to water soluble mixed
micelles by bile acids
Figure 4. Types of gallstones. Left: Cholesterol stones (more § Supersaturation of bile with cholesterol
common type 80%); Right: Pigment stones § If cholesterol phosphatidyl vesicles cannot be converted
into water soluble mixed micelles, unstable cholesterol
3. Cholesterol Stones rich vesicles remain which can aggregate into large
• OVERALL RISK FACTORS multilamellar vesicles from which cholesterol crystal
o General Risk Factors precipitate.
§ Increasing age § If not expelled from the gallbladder, these become
§ more cholesterol consumed through time thus entrapped in the gallbladder mucin gel, grow and
there is increased biliary secretion of cholesterol agglomerate forming stones
§ decreased bile acid pool § Remember: If percentages differ on all 3, you will end up
§ decreaed secretion of bile salts producing stones.
§ Female gender: 3Fs. Female, Fat, Forties (40s) § Supersaturation of bile, destabilization of bile, & bile
§ Ethnicity: Western country stasis in gallbladder

3.09 Biliary Diseases 3 of 18
 o Factors: stagnation and GB mucin
1. Supersaturation of bile o Mobile gallbladder even with supersaturation less chance
o Number 1 factor excess of bilary cholesterol either from of stone formation
oversecretion of cholesterol or hyposecretion of bile o Stability of phospholipid cholesterol vesicles
acids, phospholipids or both depends on:
o Thermodynamic requirement for formation of cholesterol § Cholesterol content
o Results from secretion of cholesterol into bile exceeding § Balance between inhibitors and promoters of
the solubilizing capacity of bile acids and phospholipids crystal formation
o Excess of biliary cholesterol • Normally: inhibitors > promoters
o Hypersecretion - increase in: § Nucleation or crystal observation time
§ Synthesis of cholesterol, with increased intake of • Influence of promoting and inhibiting factors on
cholesterol crystal appearance
§ Uptake by the liver of exogenous (via VLDL) and • Much shorter in GB bile in patients with
endogenous (via chylomicrons) cholesterol cholesterol stones
§ Hepatocanalicular transport of cholesterol § Gallbladder mucin
o Hyposecretion of bile acids or phospholipids or both • Promotes crystal nucleation and growth
§ Low rate of cholesterol 7-alpha hydroxylation • Mixture of high MW glycoprotein, layered at the
(rate limiting step in conversion of cholesterol to bile mucosal surface of GB wall
acids using7-alpha hydroxylase), genetic defect or • Forms viscous bed facilitating nucleation and
age. Bile contains more cholesterol than bile acids aggregation of crystal
and becomes lithogenic. • Stimulated by deoxycholic acid
§ Ileal defect (ileal resection) leading to impaired
• Inadequate GB contraction leads to mucin
absorption and increased fecal loss of bile acids
accumulation and formation of crystals
resulting to low amounts of bile acids in the
3. Stasis of bile in GB
enterohepatic circulation; becomes lithogenic
o Abnormal GB emptying in those with stones
o Patients with stones have increased fasting and residual
o Obesity: more cholesterol secreted into bile due to
volume and decreased fractional emptying.
increased ingestion and synthesis
o Floating stone has high chance of obstructing the cystic
duct and preventing bile flow resulting to supersaturation
o Weight loss
and subsequently increase in GB stone formation
§ Increased excretion of cholesterol in GB and
o Increased GB stones incidence
decreased GB emptying because of no or
• Fasting: lack stimulation
decreased fat intake.
• Total parenteral nutrition: no CCK
§ Mobilization of tissue cholesterol leads to increased
stimulation thus no GB contraction
biliary secretion of cholesterol while enterohepatic
• Pregnancy: Fasting and residual volume
circulation of bile acids are decreased
increase with progesterone that inhibits
§ Rapid reduction in weight due to lessened fat intake
smooth muscle contractility and impairs
decreases stimulation of GB contraction leading to
emptying
supersaturated bile and decreased emptying.
• Drugs
§ Cholesterol is heavier than water, will stay at the
bottom of the gallbladder if no contraction.
4.Pigment Stones
o Female sex hormones • MAJOR RISK FACTORS
§ Estrogens stimulate hepatic lipoprotein o Demographic factors: Asia, rural setting; poor sanitation
receptors, increase uptake of dietary § Prone to Ascariasis and Hepatic flukes
cholesterol and increase biliary cholesterol o Associated conditions:
secretion § Chronic hemolysis
§ Estrogen derivatives and oral contraceptives § Pernicious anemia
lead to decrease bile salts secretion and
§ Liver cirrhosis
decreased conversion of cholesterol to esters
§ Estrogen is protective intitally against § Cystic fibrosis
cardiovascular diseases but later in life (40’s) § Chronic biliary tract infections
depletion of increases the risk of stone § Biliary parasites
formation § Increasing age
§ Ileal disease, resection or by-pass, suffering from
2. Destabilization of bile inflammatory bowel disease (Crohn’s disease)
o Supersaturation not sufficient for lithogenesis
§ 50% have supersaturated bile but only 10 to 15%
form stones
o Majority does not have stones because time required for
cholesterol crystals to nucleate and grow is longer than
the time bile spends in the gallbladder.

3.09 Biliary Diseases 4 of 18
 Table 4. Types of Pigment Stones § Expectations after a fatty meal = films will show GB with
Black Pigment Stones Brown Pigment Stones lesser dye.
• Pure calcium bilirubinate or • Calcium salts and
polymer-like complexes unconjugated bilirubin with RADIOISOTOPES SCANS
containing mainly calcium varying amounts of cholesterol • HIDA, DIDA or 99 technitium labeled N substituted inimodiacetic
and mucin glycoprotein and proteins acids rapidly extracted and excreted
• More common in those with • Caused by increased amounts • Useful for cystic duct obstruction seen in acute cholecystitis
• Dyes absorbed by liver, secreted into biliary canaliculi, and
chronic hemolysis of unconjugated, insoluble
deposited into the GB
(increased conjugated bilirubin in bile that precipitates
bilirubin in bile), liver § Deconjugation of excess 5.Common Clinical Manifestations and Complications
cirrhosis, Gilbert’s soluble conjugated bilirubin
• Asymptomatic (majority) – stays in GB
syndrome, or cystic mono and diglucuronide
• Biliary pain/ biliary colic – stone at the neck of the GB following
fibrosis mediated by endogenous the intake of fatty food
• GB stones in ileal disease, beta glucoronidase, by • Acute cholecystitis – stone impacted in cystic duct causing
ileal resectionor ileal by-pass bacterial enzymes when inflammatory process in GB and its walls
§ enterohepatic recycling bile is infected or by • Choledocholithiasis – stone able to come out in biliary tree but
of bilirubin spontaneous alkaline is impacted from the common bile duct to the terminal portion into
• Commonly formed in hydrolysis the ampulla
gallbladder • Frequent in Asia due to high • Cholangitis – stone impacted into biliary tree and obstruction
becomes infected leading to systemic manifestations
prevalence of biliary tract
• Intermittent obstruction of cystic duct – intermittent biliary pain
infection (most common symptom), lasting 4-6 hrs
• Forms in the bile ducts • Mirizzi's syndrome - obstructs junction where cystic duct enters
• Repeated biliary infection from the distal part of common hepatic duct causing hyperbilirubinemia
repeated cholangitis and dilatation of the proximal ductal system
Ascariasis, Clonorchis • Cholecystoenteric Fistula formation - if a large stone induces
fistula formation into either the distal area of stomach, duodenum
or colon. Ending up in gallstone ileus
• Gallbladder carcinoma
4.Diagnostics Evaluation of the Gallbladder

GALLSTONES/CHOLELITIASIS
• Often found incidentally during abdominal UTZ
• 75-80% remain asymptomatic
• Belching, bloatedness, fullness or upper abdominal discomfort can
be attributed to gallstones if other diagnoses have been ruled out

ULTRASOUND
• Procedure of choice
• Accurate identification of stones (>95% sensitivity >/-1.5mm)
cheap, readily available
o Tip of 0.5 ballpen 3x
• Mobile echogenic focus with acoustic shadowing that moves
with gravity
o Echogenic focus on right upper quadrant that moves with the
movement of the patient. Acoustic shadowing found beneath
the echogenic focus.
• Incidental findings of gallstones when people do an annual
ultrasound check up.

PLAIN ABDOMINAL X-RAY

• Diagnostic only for stones containing a lot of calcium Figure 5. Schematic diagram of the natural history and complications
• Only useful for:
of gallstones
o calcified gallstones
o limey bile
o calcium infiltration of GB wall/porcelain GB 6.Asymptomatic Gallstones
o emphysematous (gas ring) NATURAL HISTORY
o cholecystitis • Cumulative risk for development of symptoms or complications
o gallstone ileus (stone passed through any fistulous tract from o 10% at 5 years
GB to intestines) o 15% at 10 years
o 18% at 15 years
ORAL CHOLECYSTOGRAPHY • Asymptomatic after 15 years are unlikely to develop symptoms
• Give patient dye the night before -> dye (iodinated tablets) will • Most patients who develop complications experience prior
concentrate inside GB -> take the films in the morning warning symptoms
• Ask patient to take fatty meal o Asymptomatic, don’t do anything; advice properly
o Determines the functional capacity o Will not rupture if asymptomatic; might rupture if
symptomatic

3.09 Biliary Diseases 5 of 18
• Complications requiring cholecystectomy are more common in • Low bile duct injury 0.2 to 0.6%
those with biliary pain • Complications lower (<4%): bile leak, wound infection,
• Symptoms: Younger > older patients (60 y.o.) pancreatitis, bleeding
• Risk of developing symptoms or complications requiring surgery is • Advantages:
1 to 2% per year. o Shorter hospital stay and convalescences
o Minimal disability
6.Surgical Treatment o Decreased cost

RECOMMENDATIONS FOR CHOLECYSTECTOMY

7.Non-Surgical Treatment
• Symptoms frequent or severe enough to interfere with daily
routine
• Presence of: ORAL BILE ACID DISSOLUTION: UDCA
o Prior complication of gallstone disease • UDCA reduces cholesterol saturation of bile and produce lamellar
o Underlying condition predisposing to increased risk of liquid crystalline phase in bile allowing dispersion of cholesterol
gallstone complication from stones
• Presence of underlying condition predisposing to increased risk of • Retards cholesterol crystal nucleation
gallstone complication • Dose of 10 to 15 mg/kg/day for 6 to 24 months provided:
o Calcified or porcelain GB o there is normal function of the gallbladder
o Previous attack of cholecystitis regardless of current status o stone is radiolucent
• Large gallstones (>3 cm) o < 10mm
• Gallstones in anomalous gallbladder • Complete dissolution in 50%
• Good results seen among those with stones < 5 mm
ASYMPTOMATIC • Cost for dissolution dose of UDCA is higher than lap
• Not recommended due to low risk of biliary colic, complications, cholecystectomy
and gallbladder cancer
• 60 to 80% remain asymptomatic up to 25 years ESWL: EXTRACORPOREAL SHOCKWAVE LITHOTRIPSY
• 2 to 4% probability of developing symptoms within 5 years after • Limited role in treatment of bile duct stone resistant to endoscopic
diagnosis and decreases to 1 to 2% subsequently to 0.1 to 0.3% extraction
yearly incidence of complications
• Does NOT prolong life expectancy MEDICAL PROPHYLAXIS
o Risk of complication counterbalanced by operative risk • Obese patients during rapid weight loss or bariatric surgery
o Cost of expectant management without prophylactic • UDCA at 600 mg/day only 3% developed gallstones
cholecystectomy until symptomatic or complications occur • Gastric banding risk of gallstones decreased from 30 to 8%
are lower than of an active approach
• Prophylactic cholecystectomy SYMPTOMATIC TREATMENT OF BILIARY COLIC
o Increased risk of gallbladder cancer (presence of porcelain • Analgesics with spasmolytic drugs: HNBB (hyacone
GB) NButylbromide) or Buscopan, painkillers (Tramadol, Ketorolac,
o Patients with large stones > 3 cm NSAIDS)
o Patchy calcification of GB • Opiates: pethidine or buprenorphine
o Patients with small stones <1cm o For the gallbladder, use opiates
o Younger patients o Do NOT use opiates if you are thinking it is an obstruction of
o Younger patient diagnosed with small stones can be treated the ampulla of Vater due to ampulla spasm
surgically because the stones have the propensity to be • Nitroglycerin: for smooth muscle relaxation, relieves spasm, but
excreted in the cystic duct may cause hypotension/ circulatory collapse
o Patients with gallstones and polyps >1cm
o Seafarers whether symptomatic or not should have their C. BILIARY PAIN
gallbladders removed even if the lesion is only a polyp as 1. Pathophysiology
prophylaxis
• Intermittent obstruction of the cystic duct without acute
SYMPTOMATIC inflammation of the gallbladder
• Pain – more complications of cholecystectomy • Intermittent pain as soon as the stone migrates up in the portion
• For as long as you are asymptomatic, you do not need the of the neck or the cystic duct
surgery. But once you start to develop the symptoms and it
becomes frequent, surgical consult must be sought. 2. Clinical features
• Recommend surgery: • Severe, poorly localized, steady ache or fullness, RUQ or
o If symptoms appear and affect patients’ normal epigastric with radiation to the interscapular area, right scapula, or
activity shoulder
o Signs of prior GB stone disease (ex. GB wall • Visceral, growing in intensity over 15 minutes remaining
thickening on UTZ due to repeated attacks of constant for about 1 to 6 hours
cholecystitis) o Often associated with nausea
o Pre-morbid state that predisposes increased risk o Subsides gradually or rapidly
of GB complication (ex. DM, chronic pulmonary • Steady rather than intermittent
disease, chronic coronary disease, chronic renal o Colic is a misnomer
failure) • Frequency of attacks varies from days to months
• Gas, bloating, flatulence and dyspepsia not related to stone
LAPAROSCOPIC CHOLECYSTECTOMY
• Not really biliary colic, per se, but it maintains or becomes
• Minimal access • Occurrence may vary from days to months, or once a year
• Conversion to open cholecystectomy <5% depending on the amount of fatty food taken in
• Low death rate <0.1%

3.09 Biliary Diseases 6 of 18
 § Escherichia coli, Klebsielle spp., Streptococcus spp.,
3. Physical Findings Clostridium spp.
• Mild to moderate epigastric/RUQ tenderness during an attack
2. Clinical features
with residual tenderness lasting for days
• Often normal • 75% preceded by attacks of biliary pains
• Maximum physical findings you can get is when there is acute • Visceral epigastric pain gives way to moderately severe localized
distention of the gallbladder at the time pain in the RUQ, radiates to the back, right shoulder
• Nausea with vomiting
4. Laboratory Findings • Pain of > 6 hours favors cholecystitis over biliary pain
• Pain of 1-6 hours that does not recur favors biliary pain
• Usually normal unless stone is able to come out and block the
biliary tree • TRIAD
o Sudden onset of RUQ tenderness
• Elevated bilirubin, alkaline phosphatase, or amylase suggest co-
o Fever
existing bile duct stones
o Leukocytosis on examination
5. Diagnostics Work-up
3. Physical Findings
• Ultrasonography is adequate already
• Oral cholecystography • Fever but <102ºF (38.89ºC) unless with gangrene or
perforation
• Meltzer-Lyon Test
o Bile examination for cholesterol crystals • Positive Murphy’s sign - right subcostal tenderness with
o Not routine - done academically when you do not see inspiratory arrest
anything on ultrasound, and you highly suspect that there is • Palpable gallbladder in 33% of patients especially those with first
crystallization of cholesterol attack
o Detects whether cholesterol crystals are being secreted in the • Mild jaundice in 20%
biliary tree o <3 mg% in bilirubin level
o That would entail the patient to be sent for ERCP to collect • Ictericia would be transient
the bile coming out of the ampulla and sending it to the lab for
cholesterol crystal determination 4. Laboratory Findings
• Leukocytosis with band forms
6. Natural History
• Elevated bilirubin, transaminases, and alkaline phosphatase
• After initial attack, 30% no further symptoms • Suspect bile duct stone if bilirubins is >4mg/dL
• Symptoms develop in others at a rate of 6% per year
• Severe complications at a rate of 1-2% per year 5. Diagnostics Work-up
• First attack: Observe, advise the patient to avoid fatty food and
buffet restaurants • Ultrasound
• Usual patients are call center agents who binge eat after o Calculi in 95%
prolonged fasting (12 hours duty) leading to biliary pain § Thickened wall
§ Pericholecystic fluid
7. Treatment § Dilatation of bile duct (with or without)
• HIDA scan (gold standard before)
• Watchful observation o (+) Non-visualization of GB – obstruction that happens on
• Elective laparoscopic cholecystectomy: send them to a the neck or the cystic duct
surgeon
• Intraoperative cholangiography (IOC) if warranted 6. Natural History
• From 2019B
o First attack: Observe • 75% resolves spontaneously in 7 to 10 days even without
o Two times in 6 months: Elective surgery – just treat them with adequate antibiotics
laparoscopiccholecystectomy o 25% recurrence within 1 year and 60% will have at least one
o History of jaundice: IOC (intraoperative cholangiography) if recurrent bout within 6 yrs
warranted or MRI or MRCP (to document that there’s no • 25% developes complication of acute cholecystitis
biliary obstruction) o 10% complicated by localized perforation
o If there’s a history of tea-colored urine and associated with o 1% free perforation and peritonitis
jaundice: Direct laparoscopic cholecystectomy • Surgeons also do not want to operate on an acute cholecystitis
because it is difficult and bloody – acutely inflamed gallbladder
D. ACUTE CHOLECYSTITS • Cure the acute insult first, make it mature for them to have ease of
1. Pathophysiology dissection
• Impacted stone in the cystic duct with acute inflammation of 7. Treatment
the gallbladder
• Inflammation not only of the wall of the gallbladder but also • Antibiotics
biochemically • Early laparoscopic cholecystectomy possibly with IOC if feasible;
o Mechanical inflammation due to increased intraluminal otherwise, open – done if patient does not respond to
pressure and distention with resulting ischemia of the antimicrobials
gallbladder mucosa and wall • ERCP or bile duct exploration for bile duct stones – done if there
o Chemical inflammation due to release of lysolecithin due to is a concomitant biliary tract obstruction
action of phospholipase on lecithin
o Bacterial inflammation in 50 to 85% – usually gram
negative organisms

3.09 Biliary Diseases 7 of 18
TOKYO GUIDELINES 2013: Diagnostic Criteria and Management
for Acute Cholecystitis

• Local Signs of Inflammation

o Murphy’s sign (inspiratory arrest during palpation of the
RUQ)
o RUQ mass/pain/tenderness
• Systemic signs of Inflammation
o Fever
o Elevated CRP
o Elevated WBC
• Imaging Findings
o There should be evidence of thickening of the mucosal
wall of the gallbladder or presence of stones within the
gallbladder or ducts
o Acute hepatitis, other acute abdominal diseases and
chronic cholcystitis should be included
• DEFINITE DIAGNOSIS
Figure 6. Algorithm used to diagnose and manage the different
o 1 item in A and 1 item in B are positive
classification of acute cholecystitis based on severity. See Appendix
o The imaging findings (C) confirms the diagnosis when
for larger picture.
acute cholecystitis is suspected clinically

SEVERITY CLASSIFICATION FOR ACUTE CHOLECYSTITIS

ORGANISMS THAT CAUSE BILIARY INFECTIONS:
Table 5. Severity Classification for Acute Cholecystitis
Table 6. Common microorganisms isolated from BILE cultures
MILD (Grade I) MODERATE SEVERE
(Grade II) (Grade III ) among patients with acute biliary infections

• Does not meet • WBC Organ

criteria for grade II >18,000/mm3 dysfunction Isolated microorganisms Proportions of isolated
& III • Palpable tender • CVS from bile cultures microorganisms (%)
• Acute cholecystitis mass in RUQ (hypotension
Gram (-) organisms
in a healthy • Duration of requiring
treatment with Escherichia coli 31-44
patient with no complaints >72
organ dysfunction hours dopamine Klebsiella spp. 9-20
• Only mild • Marked local >5ug/kg per Pseudomonas spp. 0.5-19
inflammatory inflammation minute or any Enterobacter spp. 5-9
changes in the (biliary peritonitis, dose of Acinetobacter spp. -
gallbladder hepatic abscess, dobutamine) Citrobacter spp. -
• Cholecystectomy is gangrenous • Decreased Gram (+) organisms
safe and low risk cholecystitis, sensorium Enterococcus spp. 3-34
procedure emphysematous • PaO2/FiO2 Streptococcus spp. 2-10
cholecystitis) ratio < 300 Staphylococcus spp. 0
• Oliguria, Anaerobes 4-20
* Laparoscopic creatinine >2.0
Others -
surgery should be mg/dL
done within 96 hours • PT, INR > 1.5
after onset • Platelet count <
100,000 Table 7. Common isolates from patients with bacteremic biliary tract
infections cultures among patients with acute biliary infections
• In terms of treatment of each classification of acute cholecystitis: Isolated microorganisms Proportions of isolates (%)
from BLOOD cultures Community Healthcare
o For mild or grade 1 acute cholecystitis, supportive care and
antimicrobials are enough for initial management. However, Gram (-) organisms
Escherichia coli 35-62 23
if the disease is unresponsive to the initial management, an
Klebsiella spp. 12-28 16
early laparoscopic cholecystectomy can be done.
Pseudomonas spp. 4-14 17
o For grade 2 and grade 3 acute cholecystitis, similar initial
Enterobacter spp. 2-7 7
management is followed (supportive care, organ support
Acinetobacter spp. 3 7
and antibiotics) but the main difference is that the patient is Citrobacter spp. 2-6 5
closely monitored and early detection is important when the Gram (+) organisms
patient is responding or not to the initial management. Enterococcus spp. 10-23 20
Streptococcus spp. 6-9 5
Staphylococcus spp. 2 4
Anaerobes 1 2
Others 17 11
Please see Appendix for a larger table

3.09 Biliary Diseases 8 of 18
 2. Clinical Features
EFFICACY OF ANTIMICROBIALS ON ACUTE BILIARY • Jaundice
INFECTIONS:
• Right upper quadrant pain
Please see Appendix for the tables
3. Diagnosis and Treatment
• A local antimicrobial susceptibility patterns (antibiogram) should
• Ultrasound (US)
be considered for use
o Stone at the cystic duct with dilatation of the common hepatic
• Ampicillin/sulbactam has little activity left against Escherichia
duct NOT the common bile duct
coli. It is removed from the North American guidelines
• ERCP
• Fluoroquinolone use is recommended if the susceptibility of
o Dilated intrahepatic ducts with extrinsic compression of
cultured isolates is known or for patients with b-lactam allergies.
the common hepatic duct
Many extended-spectrum b-lactamase (ESBL) producing Gram-
o Fistula
negative isolates are fluoroquinolone-resistant
§ You do not see the shadow of the stone within the
• Anti-anaerobic therapy, including use of metronidazole,
common bile duct but a defect that produces a
tinidazole, or clindamycin, is warranted if a biliary-enteric
compression deformity at the area where the cystic duct
anastomosis is present. The carbapenems,
encroaches the common hepatic duct
piperacillin/tazobactam, ampicillin/sulbactam, cefmetazole,
• Preoperative diagnosis needed to guide surgery and prevent bile
cefoxitin, flomoxef, and cefoperazone/sulbactam have sufficient
duct injury
anti-anerobic activity for this situation
• Vancomycin is recommended to cover Enterococcus spp. for
F. CHOLEDOCHOLILITHIASIS
grade III community-acquired acute cholangitis and
1. Pathophysiology
cholecystitis, and healthcare-associated acute biliary
infections. Linezolid or daptomycin is recommended if • Intermittent obstruction of the bile duct
vancomycin-resistant Enterococcus (VRE) is known to be • 10-15% of patients with cholelithiasis
colonizing the patient, if previous treatment included vancomycin,
and/or if the organism is common in the community 2. Clinical Features
• Often asymptomatic because stones can float
E. MIRIZZI’S SYNDROME • Symptoms not distinguishable from biliary pain
1. Pathophysiology • Predisposes to cholangitis and acute pancreatitis.
• Impacted stone in the gallbladder neck or cystic duct with extrinsic o caused by an obstruction of the distal portion of the duct and
compression of the common hepatic duct from accompanying would lead to stagnation of bile which will result to a bacterial
inflammation of the fistula infection

3. Physical Findings
• Completely normal if obstruction is intermittent
• Jaundice with pain in complete obstruction

4. Laboratory Findings
• Elevated bilirubin and alkaline phosphatase
• Markedly elevated bilirubin suggests malignant obstruction or
coexisting hemolysis
• Transient spike in transaminases or amylase suggest passage of
stone

5. Diagnosis and Treatment

• Ultrasound
• Percutaneous transhepatic cholangiography (PTC)
• Cholecystectomy
• ERCP
o Advantage: both diagnostic AND therapeutic
Figure 7. Pathogenesis of Mirizzi’s syndrome. Below the cystic o Findings: stone floating in the CBD or common hepatic duct
duct is the common bile duct, above the cystic duct is the common – may do papillotomy
hepatic duct, and so the cystic duct tells you where you are. The • Endoscopic US - done when nothing is seen in ERCP or US
compression happens at that junction and you cannot have • MRCP
dilatation of the distal common bile duct because the obstruction is o Will give you a very good road map of the gallbladder and
higher. This only happens when you have a stone in the distal the biliary tree from the intrahepatic to extrahepatic
portion; distal to the insertion of the cystic duct. In Mirrizi’s regions
syndrome, there is dilatation of the common hepatic duct and o Allows visualization of biliary tree
intrahepatic radicles. • Cholecystectomy

3.09 Biliary Diseases 9 of 18
 § Difference between obstruction and hepatocellular form
6. Criteria for high probability for simultaneous of jaundice
choledocholithiasis with gallstones • Reynold’s Pentad – Charcot’s Triad + hypotension + Mental
• Dilated CBD, > 6-8mm, hyperbilirubinemia, elevated GGT, alkaline confusion
phosphatase and/or ALT o Suggestive of gram negative sepsis
• CBD dilated > 10mm in presence of gallbladder stones o Co-exist in 15%
• Direct evidence of stone in bile duct •
G REMEMBER:
7. Natural History • Acute Cholecystitis Triad – RUQ pain, fever, leukocytosis
• Not well defined • Charcot’s Triad – RUQ pain, jaundice, fever
• Complications are more common and more severe than • Reynold’s Pentad – fever, jaundice, RUQ pain, hypotension,
asymptomatic stones in the gallbladder mental status changes

8. Stones
3. Laboratory Findings
• Primary stones in the bile duct are usually pigment stones
• Leukocytosis
o Hepatobiliary parasitism (liver flukes) or chronic recurrent
• Serum bilirubin > 2 mg/dL in 80%
cholangitis
• Elevated alkaline phosphatase
o Congenital anomalies of the bile ducts
§ Caroli’s disease: choledochal cysts • Blood culture usually positive (+) especially during chills
o Dilated, sclerosed or strictured ducts and fever spikes
o MDR3 (ABCB4) gene defect leading to impaired biliary
phospholipids secretion 4. Diagnostics and Treatment
• Ultrasound – looks for gallbladder stones and bile duct
G. CHOLANGITIS dilatation
• Infection of the common bile duct that happens when an • ERCP – diagnostic AND therapeutic
obstruction is present • Percutaneous Transhepatic Biliary Drainage (PTBD)
& Clinical syndrome characterized by fever, jaundice, and o If failed ERCP
abdominal pain that develops due to stasis and infection in the o If the patient is too toxic
biliary tract o If there is an interventional radiologist available, initial
management would be drainage of biliary tree and then
7. Pathophysiology start on broad spectrum antibiotics
• Obstruction of the bile ducts → bile stasis • Antibiotics for Gram negative and anaerobic organisms
• Bacterial superinfection of stagnant bile and Enterococcus spp.
• Early bacteremia • Cholecystectomy
• Non-suppurative Acute Cholangitis U if there’s a gallstone and you have cleared up the duct
o Most common with an ERCP, you proceed with cholecystectomy.
o May respond relatively rapidly to supportive measures and to
treatment with antibiotics 5. TOKYO GUIDELINES 2013: Diagnostic Criteria and
Management for Acute Cholangitis
• Suppurative Acute Cholangitis
o (+) pus under pressure in a completely obstructed ductal
system → symptoms of severe toxicity → mental confusion, Table 8. Diagnostic Criteria for Acute Cholangitis
bacteremia, and septic shock 1. Fever and/or shaking chills (T>38)
o Relatively poor response to antibiotics A. Systemic 2. Laboratory data: evidence of
Inflammation inflammatory response (WBC
o Multiple abscessed often present <4000, >10000; CRP ≥ 1mg/dL)
o Mortality rate approaches 100% unless prompt 1. Jaundice (total bilirubin ≥ 2mg/dL)
endoscopic/surgical relief of the obstruction and drainage of B. Cholestasis 2. Abnormal liver function tests (ALP,
infected bile are carried out GTP, AST, ALT >1.5 x STD)
1. Biliary dilatation
C. Imaging
2. Evidence of etiology on imaging
2. Clinical Features and Physical Findings Findings
(stricture, stone, stent, etc.)
• Fever – 95% • Suspected Diagnosis – 1 item in A, 1 item in either B/C
• RUQ tenderness – 90% • Definitive Diagnosis – 1 item in A, 1 item in B, 1 item in C
• Jaundice – 80% • Other factors which are helpful in diagnosis of acute cholangitis
• Peritoneal signs – 15% o Abdominal pain – RUQ/upper abdominal
• Mild and transient pain often accompanied by chills o History of biliary disease – gallstones, previous biliary
• Charcot’s Triad in 70% procedures, placement of a biliary stent.
o Pain, Jaundice, and Fever • In acute hepatitis, marked systematic inflammatory response is
§ Obstruction first → pain, jaundice, stagnation of bile → observed infrequently.
bile gets secondarily infected • When differential diagnosis is difficult, virological and serological
§ Versus hepatitis triad (fever → pain → jaundice) tests are required

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3.09 Biliary Diseases 10 18
 Table 9. Retrospective comparison of various diagnostic criteria of
acute cholangitis in a multi-center study in Japan.
Charcot’s TG07 The first draft TG13
Triad (%) (%) criteria (with (%)
abdominal pain
and history of
biliary disease)
(%)
Sensitivity 26.4 82.6 95.1 91.8
Specificity 95.9 79.8 66.3 77.7
[Positive Rate]
Acute 11.9 15.5 38.8 5.9
Cholecystitis

Table 10. Severity Classification for Acute Cholangitis

• Acute cholangitis +
• Organ Dysfunction Figure 8. Tokyo Guideline 2013. Flowchart Management for
o CVS (hypotension requiring treatment with
Actue Cholangitis
dopamine ≥ 5 ug/kg per min or any dose of
Severe Dobutamine See Appendix for larger figure
(Grade III) o Neuro (↓ sensorium)
o Pulmo (PaO2/FiO2 ratio < 300) NOTE: Similar microorgranisms and antimicrobials as Acute
o Renal (oliguria, creatinine > 2.0 mg/dL) Cholecystitis. SEE APPENDIX for the tables
o Hepatic (PT INR> 1.5)
o Hema (PC < 100,000) H. ACALCULOUS CHOLECYSTITIS
• Any 2 of the ff: 1. Pathogenesis
o WBC < 4000, > 12000/mm3
B. Moderate o High fever ≥ 39 deg C • Associated with serious trauma or burns, postpartum period
(Grade II) o Age ≥ 75 following prolonged labor, orthopedia surgery, or any major surgery
o Hyperbilirubinemia (TB ≥ 5 mg/dL) • Prolonged parenteral hyperalimentation
o Hypoalbuminemia (<STD x 0.7)
U patients on prolonged fasting given hyperalimentation to
C. Mild Does NOT meet criteria for Grades II and III at
(Grade I) initial diagnosis maintain nutritional status
U • Vasculitis, obstructing GB CA, diabetes mellitus, torsion of the GB,
U The severity of acute cholangitis is classified as follows: unusual bacterial infection of the GB
o Grade III (severe) – presence of organ dysfunction o Leptospira, Streptococcus, Salmonella, Vibrio cholera
o Grade II (moderate) – risk of increased severity without G Manifestations indistinguishable from calculous type but the
early biliary drainage setting of acute GB inflammation complicating a severe underlying
o Grade I (mild) – U Go with an antibiotic and then refer to a illness is characteristic
surgeon or interventional radiologist depending on the overall
picture 2. Diagnostic tests and Management
o The severity assessment criteria are very important for • Ultrasound, CT, or radioisotope scan
determining the treatment strategy for acute cholangitis o Large, tense, static GB without stones and with evidence of
especially for Grade II cases which may progress to Grade III poor emptying over a prolonged period
without immediate intervention. • Early diagnosis because early surgical intervention is warranted
o Treatment of acute cholangitis requires ‘‘treatment for causes’’
for cases with any severity, along with the administration of I. EMPHYSEMATOUS CHOLECYSTITIS
antimicrobial agents and biliary drainage. U Emphysematous meaning there is air in the mucosa or wall of the
o Early diagnosis, early biliary drainage and/or treatment for GB
etiology, and antimicrobial administration are fundamental • Acute cholecystitis with ischemia or gangrene of the GB wall
treatments for acute cholangitis classified not only as Grade and infection by gas-forming organisms
III (severe) and Grade II (moderate) but also Grade I (mild). o Persistent pain even at mild touch
o Therefore, it is recommended that patients with acute & Like other acute cholecystitis patients, they usually present
cholangitis who do not respond to the initial medical treatment with RUQ pain, nausea, vomiting, and low-grade fever
(general supportive care and antimicrobial therapy) undergo & Peritoneal signs are usually absent
early biliary drainage or treatment for etiology & Crepitus in the abdominal wall adjacent to the gall bladder
may rarely be detected but when (+) → an important clue to
the diagnosis
• Anaerobes (Clostridium welchii or Clostridium perfringens) or
aerobes like E. coli
• Plain film
o (+) gas in GB lumen, dissecting within the GB wall forming a
gaseous ring

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3.09 Biliary Diseases 11 18
 U You don’t need UTZ because the air in the GB wall will be
able to demonstrate the area of the GB. Any round/oblong 1. Pathogenesis and Clinical Features
filling defect in the RUQ, in a patient with manifestions of AC • Erosion of a stone through the GB wall into the adjacent bowel
may have emphysematous cholecystitis. o Most to least common: fistulas in the duodenum > hepatic flexure
of colon > stomach and jejunum
Diagnostics & Treatment • Signs and symptoms similar to acute cholecystitis but fistula may
• Plain abdominal films – Gas in the gallbladder fossa be silent
• Ultrasound and CT scan – If you don’t see the gas, ask for CT • Stones > 25 mm especially in elderly women – may produce bowel
scan
obstruction or gallstone ileus
• Requires immediate operation – send the patient to surgery
• Terminal ileum is the common site
o Early cholecystectomy – due to high morbidity and
mortality rates • Bouveret’s Syndrome – cholecystoenteric fistula creates gastric
• Intravenous antibiotics with anaerobic coverage outlet obstruction
o Make sure you have strong antimicrobial coverage - o Manifested by jaundice, RUQ pain, later bouts of vomiting
cover for gram negative (-) and anaerobic infections upon eating

J. COMPLICATIONS OF CHOLECYSTITIS
• Empyema
o Progression of acute cholecystitis with persistent cystic duct
obstruction → superinfection of the stagnant bile with pyogenic
organism
o Gram (-) sepsis and/or perforation
• Hydrops or Mucocoele
o Results from prolonged obstruction of the cystic duct
usually by a large solitary stone
o Progressive distention by mucus or clear transudate
produced by mucosal epithelial cells
• Gangrene & Perforation – non-operation of complications put the
patient at risk for these
• Gallstone Ileus
o Intestinal obstruction due to passage of a large gallstone into
Figure 10. Left: Impacted gallstone; Right: Gastric outlet
the bowel lumen
obstruction.
o No prior history of biliary tract symptoms or complaints
• Fistula formation 2. Diagnosis
o Adjacent organ with adhesion
• Plain abdominal films
o Duodenum, hepatic flexure of the colon, stomach or jejunum,
o Aerobilia
abdominal wall, and renal pelvis
o Small bowel obstruction
U Dependent on where the stone gets out and the closest
o Calcific density in RLQ
organ within
• Contrast GI series – may reveal the fistula
K. CHOLECYSTOENTERIC FISTULA
3. Treatment
• Cholecystoduodenal fistula – suspected if you have prolonged
GB stones + distention of the abdomen at the same time the • Fistula from solitary stone may close spontaneously
patient started to present with manifestation • Cholecystectomy and bowel closure
• Gallstone ileus
o Requires emergency laparotomy
o Delay in diagnosis lead to a 20% mortality

L. PORCELAIN GALLBLADDER
1. Pathogenesis and Clinical Features
• Intramural calcification of the GB walls usually in association
with stones
o Calcium salt deposition within the wall of a chronically inflamed
GB
• No symptoms attributable but predisposes to GB CA
G GB Carcinoma – late complication in 20%
• Limey (Milk of Calcium) bile – calcium salts in the GB lumen
produce precipitation and diffuse hazy opacification of bile or a
layering effect on plain abdominal XR

Figure 9. Cholecysto-duodenal fistula formation.

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3.09 Biliary Diseases 12 18
2.Diagnostics & Treatment
• Plain abdominal films with (+) intramural calcification
• Treatment: Cholecystectomy to prevent GB Carcinoma

Figure 11. Porcelain gallbladder in ultrasound

G SEEN ON PLAIN ABDOMINAL FILM: Figure 12. Adenomyomatosis. Different types include Generalized,
• Radiolucent stones Fundic and Segmental adenomyomatosis.
• Emphysematous GB
• Porcelain GB 2.Cholesterolosis

• Abnormal deposition of lipids, cholesterol esters within

macrophages in the lamina propria of the GB wall
M. POSTCHOLECYSTECTOMY COMPLICATION • Strawberry Gallbladder – diffuse form; brick red
gallbladder with speckled bright yellow flecks of lipid
• Early
o Atelectasis & Localized form shows solitary or multiple “cholesterol polyps”
studding the gallbladder wall
o Abscess formation
o Biliary enteric fistula
o Bile leaks – for those with difficult surgeries

N. POSTCHOLECYSTECTOMY SYNDROMES
• Biliary strictures
• Retained biliary calculi
• Cystic duct stump syndrome – long cystic (> 1 cm) cystic duct
remnant
• Stenosis or dyskinesia of the sphincter of Oddi
• Bile salt-induced diarrhea or gastritis

O. HYPERPLASTIC CHOLECYSTOSES
• Excessive proliferation of normal tissue

1.Adenomyomatosis
• Benign proliferation of GB surface epithelium with gland-like Figure 13. Strawberry Gallbladder. The yellow particles are cholesterol
formations, extramural sinuses, transverse strictures and/or crystals that have accumulated.
fundal nodule (adenoma or adenomyoma) formation
• If presenting with persistent hyperplastic cholecystoses, P. PRIMARY SCLEROSING CHOLANGITIS
undergo elective cholecystectomy • An autoimmune disorder
U The only problem is it should not produce symptoms • Often asymptomatic
because the problem is in the wall of the gallbladder. But U Usually found among females
it is a pre-malignant condition; that is why if it’s becoming • Unexplained elevation of alkaline phosphatase
persistent, perform elective cholecystectomy. &Patients with PSC often present with signs and symptoms of
chronic or intermittent iliary obstruction:
§ RUQ abdominal pain, Pruritus, fatigue, may or may
not have jaundice (Once jaundice presents, there is
marked cholestatic pattern of liver function test)
U Markedly elevated alkaline phosphatase (4-8 times
the upper limit)
• MRCP and ERCP

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3.09 Biliary Diseases 13 18
 o Cholangiographic of choice techniques of choice in
suspected cases
U Multifocal stricturing with normal or dilated areas of intra- or
extra-hepatic biliary tree
G Narrowing and beading of bile ducts
U So if you hear narrowing and beading of the bile ducts,
think of primary sclerosing cholangitis
• Progressive inflammatory, sclerosing, and obliterating disease of
the extrahepatic and intrahepatic ducts
• 70%-90% will have inflammatory bowel disease, particularly
ulcerative colitis
• 8%-15% lifetime risk for cholangiocarcinoma or primary cancer of
the bile duct
• Similar treatment for other autoimmune disorders
o No primary drugs to treat PSC (either depend on steroids or
ursodeoxycholic acid because you do not want the bile to be
supersaturated with cholesterol as there will be stone
formation in the dilated segments)
Figure 15. Biliary Atresia and Hypoplasia.

R. CHOLEDOCAL CYST

Figure 14. Narrowing and beading of bile ducts.

• Histologic Features
o Fibrous obliteration of small bile ducts with concentric
replacement by connective tissue in an onion skin pattern
o Evidence of liver cirrhosis upon biopsy

Table 11. Histologic staging of primary sclerosing cholangitis.

Stage Features
1 Enlargement, mononuclear cell infiltration and Figure 16. Types of Choledocal Cyst. Photo taken from ppt.
scarring of portal triads
2 Fibrosis extending to the surrounding • Type I Cysts: Most common, exhibit segmental or diffuse
parenchyma fusiform dilatation of the bile duct (Gextrahepatic)
3 Bridging fibrosis o Several varieties of Type I cysts, accounting for 80%
4 Cirrhosis to 90% of cases, exhibit segmental or diffuse fusiform
dilatation of the bile duct

Q. CONGENITAL ANOMALIES
• Type II Cysts: Consist of a true choledochal diverticulum in
1. Biliary Atresia and Hypoplasia
the common bile duct
• Usually found in newborns and is managed with Kasai
procedure or hepatic portoenterostomy, which should • Type III Cysts (Choledochocele): Consist of dilatation of
be performed as soon as possible, or liver the Gintraduodenal (distal) portion of the bile duct
transplantation if there is delayed diagnosis or treatment
failure
• Type IV Cysts: Subdivided into types
o Kasai procedure: those who have a circumoval
o IVa (Multiple intrahepatic and extrahepatic cysts)
operation in the upper abdomen; it is basically a
o IVb (Multiple extrahepatic cysts only): Either
reconstruction of the ductal system
uncommon or may overlap with type I
U If you have biliary atresia, you would have to have an
operation
U Biliary atresia is not compatible with long life • Type V (Caroli's Disease) Cysts: Consist of single or
• Atretic and hypoplastic lesions of the extrahepatic and multiple dilatations of only the intrahepatic ductal system;
large intrahepatic bile ducts are the most common biliary whether it should be viewed as a form of choledochal cyst
anomalies of clinical relevance encountered in infancy is unsettled
• Clinical picture: Severe obstructive jaundice during
the first month of life with pale stools

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3.09 Biliary Diseases 14 18
S. CHOLANGIOCARCINOMA
1. Risk Factors
• Biliary-enteric drainage procedures
• Caroli's disease
• Choledochal cyst
• Cirrhosis
• Clonorchis sinensis infection
• Hepatitis C
• Hepatolithiasis
• Opisthorchis viverrini infection
• Primary sclerosing cholangitis
• Thorotrast
• Toxins (dioxins, polyvinyl chloride)
• Usually presents with painless jaundice
• Differentiate if it is pancreatic painless jaundice or
cholangiocarcinoma

2.Classification of Cholangiocarcinoma
• Anatomic classification of intrahepatic (common hepatic duct) and
extrahepatic cholangiocarcinoma
o Extrahepatic cholangiocarcinoma is sub-classified as hilar or Figure 19. Algorithm for the Management of Cholangiocarcinoma.
distal
• Bismuth-Corlette classification of hilar cholangiocarcinoma
ranging from types I to IV T. GALLBLADDER CARCINOMA
o Tumor is depicted in yellow and normal bile ducts in green • Not symptomatic
• Usually pathologic diagnosis of gallbladder that is removed, not
because the impression is gallbladder CA but because the patient
underwent cholecystectomy
• Usually a post-operative diagnosis

1. Risk Factors for Gallbladder Carcinoma

• Adenomyomatosis
• Anomolous union of the pancreaticobiliary ductal system
• Carcinogens
• Cholangiocarcinoma
• Cholelithiasis (stone size > 1 cm)
• Chronic S. typhi or paratyphi carrier status
• First-degree relative with gallbladder cancer
• Intrahepatic biliary dysplasia
• Porcelain gallbladder
Figure 17. Anatomic classification of intra and extra-hepatic • Primary sclerosing cholangitis
cholangiocarcinoma (Green: Normal; Yellow: Tumor)
III. REFERENCES
Table 12. Bismuth-Corlette classification of hilar Harrison’s Principles of Internal Medicine 19th ed.
cholangiocarcinoma. Dr. Salvador’s ppt lecture and recording
Type Location of Lesion 2019 Transcriptions
Type 1 Common hepatic duct
Type 2 Confluence of the right and left hepatic ducts
Type 3A Portion of common hepatic duct AND right
hepatic duct
Type 3B Portion of the common hepatic duct AND left
hepatic duct
Type 4 Extending to the bifurcations of both right and left
(Klatskin’s hepatic ducts or multifocal involvement
Tumor)

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3.09 Biliary Diseases 15 18
 APPENDIX

APPENDIX A. TOKYO GUIDELINE 2013 for Diagnosis and Severity Assessment of Acute Cholecystitis

APPENDIX B. TOKYO GUIDELINE 2013 for Diagnosis and Severity Assessment of Acute Cholangitis

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3.09 Biliary Diseases 16 18
 APPENDIX C. Antimicrobial recommendations for Grade I acute biliary infections

APPENDIX D. Antimicrobial recommendations for Grade II, III, and healthcare-associated acute biliary infections

Refer to Appendix C and D

a: Local antimicrobial susceptibility patterns (antibiogram) should be considered for use.
b: Ampicillin/sulbactam has little activity left against Escherichia coli. It is removed from the North American guidelines.
c: Fluoroquinolone use is recommended if the susceptibility of cultured isolates is known or for patients with b-lactam allergies. Many extended-
spectrum b-lactamase (ESBL)-producing Gram- negative isolates are fluoroquinolone-resistant.
d: Anti-anaerobic therapy, including use of metronidazole, tinidazole, or clindamycin, is warranted if a biliary-enteric anastomosis is present. The
carbapenems, piperacillin/tazobactam, ampicillin/sulbactam, cefmetazole, cefoxitin, flomoxef, and cefoperazone/sulbactam have sufficient anti-
anerobic activity for this situation.
e: Vancomycin is recommended to cover Enterococcus spp. for grade III community-acquired acute cholangitis and cholecystitis, and healthcare-
associated acute biliary infections. Linezolid or daptomycin is recommended if vancomycin-resistant Enterococcus (VRE) is known to be
colonizing the patient, if previous treatment included vancomycin, and/or if the organism is common in the community.

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3.09 Biliary Diseases 17 18
 Isolated microorganisms from bile Proportions of isolated
cultures microorganisms (%)

Gram (-) organisms

Escherichia coli 31-44
Klebsiella spp. 9-20
Pseudomonas spp. 0.5-19
Enterobacter spp. 5-9
Acinetobacter spp. -
Citrobacter spp. -
Gram (+) organisms
Enterococcus spp. 3-34
Streptococcus spp. 2-10
Staphylococcus spp. 0
Anaerobes 4-20
Others -

APPENDIX E. Common microorganisms isolated from bile cultures among patients

with acute biliary infections

Isolated microorganisms Proportions of isolates (%)

from BLOOD cultures Community- Healthcare-
acquired Infections associated
infections
Gram (-) organisms
Escherichia coli 35-62 23
Klebsiella spp. 12-28 16
Pseudomonas spp. 4-14 17
Enterobacter spp. 2-7 7
Acinetobacter spp. 3 7
Citrobacter spp. 2-6 5
Gram (+) organisms
Enterococcus spp. 10-23 20
Streptococcus spp. 6-9 5
Staphylococcus spp. 2 4
Anaerobes 1 2
Others 17 11

APPENDIX F. Common isolates from patients with bacteremic biliary tract infections
cultures among patients with acute biliary infections

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