GB and Biliary System

GB and Biliary system
Principles and management
Dr. Mahmoud W. Qandeel

Outlines
• Anatomy • Choledochal cyst
• Histology • Sclerosing Cholangitis
• Anomalies • Bile Duct Strictures
• Physiology • Carcinoma of the Gallbladder
• Diagnostic studies • Cholangiocarcinoma
• GB stones
• Acute cholecystitis
• Choledocholithiasis
• Cholangitis
• Bile duct injury

Anatomy
• The gallbladder is a pear-shaped sac, about 7 to 10 cm long
with an average capacity of 30 to 50 mL.
• When obstructed, the gallbladder can distend markedly and

contain up to 300 mL
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Histology
• The gallbladder is lined by a single, highly folded, tall
columnar epithelium that contains cholesterol and fat
globules.
• The mucus secreted into the gallbladder originates in the

tubuloalveolar glands found in the mucosa lining the
infundibulum and neck of the gallbladder, but are absent from
the body and fundus.
11
• The epithelial lining of the gallbladder is supported by a lamina
propria.
• The muscle layer has circular longitudinal and oblique fibers
12
Anomalies
• The classic description of the extrahepatic biliary tree and its
arteries applies only in about one third of patients.
• The gallbladder may have abnormal positions, be intrahepatic,

be rudimentary, have anomalous forms, or be duplicated.
• The cystic artery that supplies the gallbladder is usually a

branch of the right hepatic artery (>90% of the time).
13
• Anomalies of the hepatic artery and the cystic artery are quite common, occurring in as
many as 50% of cases.
• In about 5% of cases, there are two right hepatic arteries, one from the common hepatic
artery and the other from the superior mesenteric artery.
• In about 20% of patients, the right hepatic artery comes off the superior mesenteric
artery.
• The cystic artery arises from the right hepatic artery in about 90% of cases, but may arise
from the left hepatic, common hepatic, gastroduodenal, or superior mesenteric arteries
14
Variations in the arterial supply to the gallbladder. A. Cystic
artery from right hepatic artery, about 80–90%. B. Cystic
artery from right hepatic artery (accessory or replaced)
from superior mesenteric artery, about 10%. C. Two cystic
arteries, one from the right hepatic, the other from the
common hepatic artery, rare.
15
D. Two cystic arteries, one from the right hepatic, the
other from the left hepatic artery, rare. E. The cystic
artery branching from the right hepatic artery and
running anterior to the common hepatic duct, rare. F.
Two cystic arteries arising from the right hepatic artery,
rare.
16
PHYSIOLOGY Bile Formation and Composition
• Produces within the liver 500 to 1000 mL of bile a day.

• The secretion of bile is responsive to neurogenic, humoral, and chemical stimuli.
• Vagal stimulation increases secretion of bile.
• Hydrochloric acid, partly digested proteins, and fatty acids in the duodenum
stimulate the release of secretin from the duodenum that, in turn, increases bile
production and bile flow.
• Bile flows from the liver through to the hepatic ducts, into the common hepatic
duct, through the common bile duct, and finally into the duodenum.
• With an intact sphincter of Oddi, bile flow is directed into the gallbladder.
17
• Bile is mainly composed of water, electrolytes, bile salts, proteins, lipids, and
bile pigments.
• Sodium, potassium, calcium, and chlorine have the same concentration in

bile as in plasma or extracellular fluid.
• The pH of hepatic bile is usually neutral or slightly alkaline, but varies with
diet; an increase in protein shifts the bile to a more acidic pH
18
Bile composition
• A. 90% H2O, 10% electrolytes and organic solutes
• B.Solutes:
– Two-thirds bile acids,
– 20 % phosopholipids.
– 4% cholesterol,
– 4-5%proteins,
– <1%bilirubin
• C.Electrolytes
19
DIAGNOSTIC STUDIES
• Blood Tests
• Ultrasonography
• HIDA scan (hydroxyiminodiacetic acid)
• CT
• PTC percutaneous transhepatic cholangiography
• MRCP
• ERCP endoscopic retrograde cholangiopancreatography
• Endoscopic US
20
Gallstones
• Gallstones are found in 12% men and 24% women
• Prevalence increases with advancing age
• 10-20% become symptomatic
• Over 10% of those with stones in the gallbladder have stones in the
common bile duct
• More than 4,000 common bile ducts are cleared of stones
21
• There are many events that may promote cholelithiasis:
➢ The liver secretes too much cholesterol into the bile.

➢ The gallbladder may not be able to empty normally, so bile becomes
stagnant.
➢ The cells lining the gallbladder may not be able to efficiently absorb
cholesterol and fat from bile.
➢ There are high levels of bilirubin
22
Pathophysiology
• Three types of stones are recognised
– Cholesterol stones (15%)
– Mixed stones (80%)
– Pigment stones (5%)
23
Cholesterol Stones
• Cholesterol gallstones typically form in the following way:
– Cholesterol is not very soluble, so in order to remain suspended in fluid it must be

transported within clusters of bile salts called micelles.
– If there is an imbalance between these bile salts and cholesterol, then the bile fluid
turns to sludge.
– This thickened fluid consists of a mucus gel containing cholesterol and calcium
bilirubinate.
– If the imbalance worsens, cholesterol crystals form (a condition called
supersaturation), which can eventually form gallstones.
24
• Mixed stones are probably a variant of cholesterol stones
• 10% of gallstones are radio-opaque
• Cholesterol stones result from a change in solubility of bile constituents
• Bile acids act as a detergent keeping cholesterol in solution

• Bile acids, lecithin and cholesterol result in the formation of micelles
25
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Pigment stones
• Pigment stones are composed of calcium bilirubinate, or calcified bilirubin.

• Pigment stones can be black or brown.
• Black stones form in the gallbladder and are the more common type.
• They are more likely to develop in people with hemolytic anemia or cirrhosis
(scarred liver), TPN, Ileal resection.
• Brown pigment stones are more common in Asian populations. They contain more
cholesterol and calcium than black pigment stones and are more likely to occur in the
bile ducts. Infection plays a role in the development of these stones.
• Mixed stones.
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Clinical presentations
• Acute cholecystitis
• Empyema of the gallbladder
• Mucocele of the gallbladder
• Biliary colic
• 'Flatulent dyspepsia'
• Mirrizi's syndrome
• Obstructive jaundice
• Pancreatitis
• Acute cholangitis
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Acute cholecystitis
• 90% cases result from obstruction to the cystic duct by a stone.
• Increased pressure within the gallbladder results in an acute inflammatory

response
• Secondary bacterial infections occurs in 20% of cases of acute cholecystitis

.
• Most common organisms are E. coli, Klebsiella and strep. faecalis
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Clinical features
• Constant pain (usually greater than 12 hours duration) in right
upper quadrant
• Fever, tachycardia
• Tenderness in right upper quadrant
• Murphy's sign - guarding in right upper quadrant on deep
inspiration
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Investigation
• Ultrasound is the initial investigation of choice
• Diagnostic features on ultrasound include
– Presence of gallstones
– Distended thick-walled gallbladder
– Pericholecystic fluid
– Murphy's sign demonstrated with ultrasound probe
• If diagnostic doubt a HIDA scan may be useful

• Will show failure of isotope (hydroxyiminodiacetic acid) uptake by gallbladder
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Management
• Initial management is usually conservative
• Patient is fasted, given intravenous fluids and opiate analgesia
• Intravenous antibiotics (e.g. second generation cephalosporin) should

be given to prevent secondary infection
• 80% patients improve with conservative treatment

• If fit, should be considered for a laparoscopic cholecystectomy
34
• Timing of surgery is controversial
• Evidence now suggests that early surgery ( les than 72 hours) is safe
– Has low conversion rate
– Avoids the complications of conservative treatment failure
• If patient unfit for surgery, percutaneous cholecystotomy my be beneficial

• Particularly useful in acalculus cholecystitis
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Complications of acute cholecystitis
• Gangrenous cholecystitis
• Gallbladder perforation
• Cholecystoenteric fistula
• Gallstone ileus
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Treatment of gallbladder stones
• Asymptomatic no treatment unless risk factors of malignancy.
• Open cholecystectomy
• Today mortality is approximately 0.5%
• Morbidity includes:
– Specific complications - bile duct damage, retained stones, bile leak
– General complications - wound dehiscence, pulmonary atelectasis
37
Best is Laparoscopic cholecystectomy unless contraindicated
Pre-operative ERCP is indicated if:

– Recent jaundice
– Abnormal liver function tests ??
– Significantly dilated common bile duct ??
– Ultrasonic suspicion of bile duct stones
38
• Dissolution therapies
– High complication rate
– Poor long-term results
• Extra-corporeal shock wave lithotripsy

– Poor stone clearance
39
CHOLEDOCHOLITHIASIS
• Common bile duct stones may be small or large, single or multiple,
• Found in 10% of patients with stones in the gallbladder.
• The incidence increases with age.
– Secondary common bile duct stones (cholesterol stones) In most cases,

common bile duct stones originally form in the gallbladder and pass into the common duct
– The primary stones are associated with biliary stasis and infection
(pigment stones) form in the common duct itself duct stones are usually of the brown pigment
type and are more likely to cause infection than secondary common duct stones.
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Clinical Manifestations
• May be silent and or may cause obstruction, complete or incomplete,
• May manifest with cholangitis or gallstone pancreatitis.
• The pain caused by a stone in the bile duct is very similar to that of biliary
colic.
• Nausea and vomiting are common
• Often are discovered incidentally
• Physical examination may be normal, but mild epigastric or right upper
quadrant tenderness as well as mild icterus are common
• Severe jaundice and cholangitis in case of stone impaction
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CHOLANGITIS
• One of the two main complications of choledochal stones, the other
being gallstone pancreatitis
• Acute cholangitis is an ascending bacterial infection in association with
partial or complete obstruction of the bile ducts.
• Biliary bacterial contamination alone does not lead to clinical

cholangitis; the combination of both significant bacterial contamination
and biliary obstruction is required for its development.
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• Gallstones are the most common cause of obstruction in cholangitis; other
causes are
– Benign and malignant strictures,
– Parasites,
– Instrumentation of the ducts and indwelling stents,
– Partially obstructed biliary-enteric anastomosis.
• The most common organisms cultured from bile in patients with cholangitis include E.
coli , Klebsiella pneumoniae , Streptococcus faecalis , Enterobacter, and Bacteroides
fragilis .
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Clinical Presentation
• May present as anything from a mild, intermittent, and self-limited disease to a fulminant,
potentially life-threatening septicemia.
• The patient with gallstone-induced cholangitis is typically older and female.
• The most common presentation is fever, epigastric or right upper quadrant pain, and
jaundice.(Charcot's triad) 2/3 pt
• Reynolds pentad (e.g., fever, jaundice, right upper quadrant pain, septic shock, and mental
status changes)
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Investigation and management
• IV antibiotics
• Urgent ERCP for drainge
47
Bile duct injury
• Occurs in between 0.1% and 0.5% of patients
• Risk related to surgical inexperience and problems identifying biliary
anatomy
• Outcome improved if recognised at time of initial surgery
• For most injuries hepaticojejunostomy is the treatment of choice
• If recognition of injury is delayed then associated with higher morbidity
and mortality
• Management then requires drainage of collections and control of
sepsis
• Long-term risk include stricture formation and cirrhosis
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Acalculous Cholecystitis
• Acute inflammation of the gallbladder can occur without gallstones.
• Acalculous cholecystitis typically develops in critically ill patients in the
intensive care unit.
• Patients on parenteral nutrition with extensive burns, sepsis, major
operations, multiple trauma, or prolonged illness with multiple organ
system failure are at risk for developing acalculous cholecystitis.
• Bile stasis and ischemia has been implicated as causative factors
• Clinical manifestation
• Percutaneous cholecystectomy and cholecystectomy
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Choledochal cysts
• Choledochal cysts are congenital cystic dilatations of the
extrahepatic and/or intrahepatic biliary tree.
• They are rare—the incidence is between 1:100,000 and

1:150,000 in populations of Western countries—but are more
commonly seen in populations of Eastern countries.
• Choledochal cysts affect females three to eight times more

often than males
50
• More than 90% of patients have an anomalous
pancreaticobiliary duct junction, with the pancreatic duct
joining the common bile duct >1 cm proximal to the ampulla.
• The cysts are lined with cuboidal epithelium and can vary in size
from 2 cm in diameter to giant cysts.
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Type I, fusiform or cystic dilations of the Type II, saccular diverticulum of an extrahepatic
extrahepatic biliary tree, is the most common type, bile duct. Rare, <5% of choledochal cysts
making up >50% of the choledochal cysts
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Type III, bile duct dilatation within the Type IVa and IVb, multiple cysts, make up 5–10%
duodenal wall (choledochoceles), makes of choledochal cysts. Type IVa affects both
up about 5% of choledochal cysts. extrahepatic and intrahepatic bile ducts
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Type IVb cysts affect the Type V, intrahepatic biliary cysts, is very rare
extrahepatic bile ducts only and makes up 1% of choledochal cysts.
Caroli’s disaese
54
• Although frequently diagnosed in infancy or childhood, as many as one half of the
patients have reached adulthood when diagnosed.
• Adults commonly present with jaundice or cholangitis.

• Less than one half of patients present with the classic clinical triad of abdominal pain,
jaundice, and a mass.
• Ultrasonography or CT scanning will confirm the diagnosis.

• Endoscopic, transhepatic, or MRC is required to assess the biliary anatomy and to
plan the appropriate surgical treatment.
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• For types I, II, and IV, excision of the extrahepatic biliary tree, including
cholecystectomy, with a Roux en-Y hepaticojejunostomy are ideal.
• In type IV, additional segmental resection of the liver may be appropriate.
• The risk of cholangiocarcinoma developing in choledochal cysts is as high as 15% in

adults
56
Sclerosing Cholangitis
• Sclerosing cholangitis is an uncommon disease characterized by inflammatory
strictures involving the intrahepatic and extrahepatic biliary tree.
• It is a progressive disease that eventually results in secondary biliary cirrhosis.
• Sometimes, biliary strictures are clearly secondary to bile duct stones, acute
cholangitis, previous biliary surgery, or toxic agents, and are termed secondary
sclerosing cholangitis .
57
• It is associated with ulcerative colitis in about two thirds of patients.
• Other diseases associated with sclerosing cholangitis include Riedel's thyroiditis and
retroperitoneal fibrosis.
• Autoimmune reaction, chronic low-grade bacterial or viral infection, toxic reaction,
and genetic factors have all been suggested to play a role in its pathogenesis.
• Patients with sclerosing cholangitis are at risk for developing cholangiocarcinoma.

• Eventually, 10 to 20% of the patients will develop cancer.
58
• The mean age of presentation is 30 to 45 years, and men are affected twice as commonly as
women.
• The usual presentation is intermittent jaundice, fatigue, weight loss, pruritus, and
abdominal pain.
• Symptoms of acute cholangitis are rare, without preceding biliary tract intervention or
surgery.
• More than one half of patients are symptomatic when diagnosed.
• In several patients with ulcerative colitis, abnormal liver function tests found on routine
testing lead to the diagnosis.
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• The clinical course in sclerosing cholangitis is highly variable, but cyclic remissions
and exacerbations are typical.
• The median survival for patients with primary sclerosing cholangitis from the time of
diagnosis ranges from 10 to 12 years, and most die from hepatic failure
• The clinical presentation and elevation of alkaline phosphatase and bilirubin may
suggest the diagnosis, but ERCP, revealing multiple dilatations and strictures
(beading) of both the intra- and extrahepatic biliary tree, confirms it.
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Bile Duct Strictures
• Benign bile duct strictures can have numerous causes.
– Operative injury, most commonly by laparoscopic cholecystectomy.
– Fibrosis due to chronic pancreatitis, common bile duct stones, acute
cholangitis,
– Biliary obstruction due to cholecystolithiasis (Mirizzi's syndrome),
sclerosing cholangitis, cholangiohepatitis, and strictures of a
biliaryenteric anastomosis.
• Bile duct strictures that go unrecognized or are improperly managed may lead to
recurrent cholangitis, secondary biliary cirrhosis, and portal hypertension
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Carcinoma of the Gallbladder
• Cancer of the gallbladder is a rare malignancy that occurs
predominantly in the elderly.
• It is an aggressive tumor, with poor prognosis except when incidentally

diagnosed at an early stage after cholecystectomy for cholelithiasis.
• The overall reported 5-year survival rate is about 5%
64
INCIDENCE
• Gallbladder cancer is the fifth most common GI malignancy in Western countries.
• It accounts for only 2 to 4% of all malignant GI tumors, with about 5000 new cases
diagnosed annually in the United States.
• It is two to three times more common in females than males, and the peak incidence is in
the seventh decade of life.
• Its occurrence in random autopsy series is about 0.4%, but approximately 1% of patients
undergoing cholecystectomy for gallstone disease are found incidentally to have
gallbladder cancer
65
• Cholithiasis is the most important risk factor for gallbladder carcinoma, and up to
95% of patients with carcinoma of the gallbladder have gallstones.
• Larger stones (>3 cm) are associated with a 10-fold increased risk of cancer.
• The risk of developing cancer of the gallbladder is higher in patients with

symptomatic than asymptomatic gallstones.
66
• Polypoid lesions of the gallbladder are associated with increased risk of cancer, particularly
in polyps >10 mm.
• The calcified "porcelain" gallbladder is associated with >20% incidence of gallbladder

carcinoma. ??
• Patients with choledochal cysts have an increased risk of developing cancer anywhere in
the biliary tree, but the incidence is highest in the gallbladder.
• Sclerosing cholangitis, anomalous pancreaticobiliary duct junction, and exposure to

carcinogens (azotoluene, nitrosamines) also are associated with cancer of the gallbladder
67
• Between 80 and 90% of the gallbladder tumors are adenocarcinomas.
• Squamous cell, adenosquamous, ,and other anaplastic lesions occur

rarely.
• When diagnosed,
– about 25% of gallbladder cancers are localized to the gallbladder wall,
– 35% have regional nodal involvement and/or extension into adjacent liver,
– and approximately 40% have distant metastasis.
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• Tumors limited to the muscular layer of the gallbladder (T1) are
usually identified incidentally, after cholecystectomy for gallstone
disease.
• There is near universal agreement that simple cholecystectomy

is an adequate treatment for T1 lesions and results in a near
100% overall 5-year survival rate
69
• When the tumor invades the perimuscular connective tissue
without extension beyond the serosa or into the liver (T2
tumors), an extended cholecystectomy should be performed.
• That includes resection of liver segments IV and V, and

lymphadenectomy of the cystic duct, and pericholedochal,
portal, right celiac, and posterior pancreatoduodenal lymph
nodes
70
• For tumors that grow beyond the serosa or invade the liver or other organs (T3 and
T4 tumors), there is a high likelihood of intraperitoneal and distant spread.
• If no peritoneal or nodal involvement is found, complete tumor excision with an

extended right hepatectomy (segments IV, V, VI, VII, and VIII) must be performed for
adequate tumor clearance.
• An aggressive approach in patients who will tolerate surgery has resulted in an

increased survival for T3 and T4 lesions.
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• Patients with advanced but resectable gallbladder cancer
• are reported to have 5-year survival rates of 20 to 50%.
However, the median survival for patients with distant
metastasis at the time of presentation is only 1 to 3 months.
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Bile duct tumor
Cholangiocarcinoma
• Cholangiocarcinoma is a rare tumour of the biliary tree

• Accounts for about 1000 deaths per year in United Kingdom
• Arises from the epithelium of the biliary tract
• 25% are intrahepatic
• Often presents late with irresectable disease
• Cure rates are low and median survival is less than 12 months
• Neoadjuvant and adjuvant therapies have not improved survival
73
Risk factors
• Age
• Primary sclerosing cholangitis
• Choledocholithiasis
• Biliary papillomatosis
• Choledochal cysts
74
(Bismuth-Corlette classification)
75
Clinical features
• Most patients present with obstructive jaundice

• Pain and fever are uncommon
• Late presentation is associated with fatigue, malaise and weight loss
• Some are found incidentally when imaging is performed for other
reasons
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Diagnosis
• Liver function tests show an obstructive picture

• CA19.9 and CA125 may be raised
• Diagnosis can be confirmed by CT or MRI
• ERCP can be both diagnostic and therapeutic
• Specimens can be obtained for cytology / histology
• A biliary stent can be inserted
77
Management
• Surgery offers the only chance of cure

• Tumour is resected and biliary reconstruction is performed
• Aim is for resection with tumour free margins
• Determinants of resectability are:
– Extent of tumour
– Vascular invasion
– Hepatic lobar atrophy
– Metastatic disease
• Liver transplantation is controversial due to high recurrence rates
78

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GB and Biliary system

Principles and management

Dr. Mahmoud W. Qandeel

Dr. Mahmoud W. Qandeel

• When obstructed, the gallbladder can distend markedly and

• The mucus secreted into the gallbladder originates in the

• The muscle layer has circular longitudinal and oblique fibers

• The gallbladder may have abnormal positions, be intrahepatic,

• The cystic artery that supplies the gallbladder is usually a

• Produces within the liver 500 to 1000 mL of bile a day.

• Sodium, potassium, calcium, and chlorine have the same concentration in

➢ The liver secretes too much cholesterol into the bile.

– Cholesterol is not very soluble, so in order to remain suspended in fluid it must be

• Bile acids act as a detergent keeping cholesterol in solution

• Pigment stones are composed of calcium bilirubinate, or calcified bilirubin.

• Increased pressure within the gallbladder results in an acute inflammatory

• Secondary bacterial infections occurs in 20% of cases of acute cholecystitis

• If diagnostic doubt a HIDA scan may be useful

• Intravenous antibiotics (e.g. second generation cephalosporin) should

• 80% patients improve with conservative treatment

• If patient unfit for surgery, percutaneous cholecystotomy my be beneficial

Pre-operative ERCP is indicated if:

• Extra-corporeal shock wave lithotripsy

– Secondary common bile duct stones (cholesterol stones) In most cases,

• Biliary bacterial contamination alone does not lead to clinical

• They are rare—the incidence is between 1:100,000 and

• Choledochal cysts affect females three to eight times more

• Adults commonly present with jaundice or cholangitis.

• Ultrasonography or CT scanning will confirm the diagnosis.

• In type IV, additional segmental resection of the liver may be appropriate.

• The risk of cholangiocarcinoma developing in choledochal cysts is as high as 15% in

• It is a progressive disease that eventually results in secondary biliary cirrhosis.

• Patients with sclerosing cholangitis are at risk for developing cholangiocarcinoma.

• It is an aggressive tumor, with poor prognosis except when incidentally

• The overall reported 5-year survival rate is about 5%

• The risk of developing cancer of the gallbladder is higher in patients with

• The calcified "porcelain" gallbladder is associated with >20% incidence of gallbladder

• Sclerosing cholangitis, anomalous pancreaticobiliary duct junction, and exposure to

• Squamous cell, adenosquamous, ,and other anaplastic lesions occur

• There is near universal agreement that simple cholecystectomy

• That includes resection of liver segments IV and V, and

• If no peritoneal or nodal involvement is found, complete tumor excision with an

• An aggressive approach in patients who will tolerate surgery has resulted in an

• Cholangiocarcinoma is a rare tumour of the biliary tree

• Most patients present with obstructive jaundice

• Liver function tests show an obstructive picture

• Surgery offers the only chance of cure

• Liver transplantation is controversial due to high recurrence rates

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