Biliary tract diseases

Gallstone disease
Definition
GD – is a disease of hepatobiliary system, caused by
disorders of cholesterol and/or bilirubin metabolism,
characterized by creation of stones in gallbladder and/or bile
ducts.
 Types of Gallstones

 Cholesterol (80% of stones)

 Calcium bilirubinate (pigment) <20% of stones
 Mixed

 Cholesterol stones
Risk factors for Gallstone disease
 Cholesterol stones:
 Age
 Female gender
 Obesity
 Rapid weight loss
 Hypertriglyceridemia
 Genetic factors
 Medications: estrogen, clofibrate, ceftriaxone, sandostatin
 Terminal ileal resection
 Gallbladder hypomotility: pregnancy, diabetes, postvagotomy
 Total parenteral nutrition
 Spinal cord injury
 Risk factors for Gallstone disease
 Pigment stones:
 Chronic haemolysis
 Alcohol liver cirrhosis
 Chronic infections of bile ducts, parasite infections
 Helminthosis
 Increasing age
 Demographic factors (mostly rural areas in asian
countries)
 Gallstone disease
 Mechanisms of cholesterol gallstone formation:
 Increased biliary secretion of cholesterol results in
cholesterol supersaturation of bile
 Gallbladder hypomotility (decreased and delayed emptying
of gallbladder) causes stasis of bile
 Excess secretion of mucus into the gallbladder, the formation
of a gel layer, and stasis causes cholesterol to nucleate and
cholesterol crystals to be deposited. Cholesterol crystals
precipitate and form a “stone”
 Gallstone disease
 Mechanisms of cholesterol gallstone formation (cont’d):
 Biliary sludge (BS) may be a precursor form of gallstone
disease. BS is a thick mucous material that upon microscopic
examination reveals lecithin-cholesterol crystals, cholesterol
monohydrate crystals, calcium bilirubinate, and mucin thread
of mucous gels.
 The presence of BS implies two abnormalities:
1. The normal balance between gallbladder mucin secretion and
elimination has become deranged
2. Nucleation of biliary solutes has occured
Pathogenesis of
cholesterol
gallstone
formation
 Pathogenesis of pigment gallstone
formation
 The pathogenesis of black pigment gallstones is less understood than
that of cholesterol gallstones. Bilirubin is secreted predominantly in
the conjugated form, but deconjugation occurs either
nonenzymatically or by the action of endogenous β‐glucuronidase.
 Bile salts reduce the driving force for calcium bilirubinate
precipitation in two ways:
 (1) by partially solubilizing unconjugated bilirubin
 (2) by complexing with calcium to reduce the free concentration levels.
Calcium also precipitates as inorganic calcium salts, such as calcium
phosphate and calcium carbonate.
 After calcium bilirubin granules are formed, their clearance from the
gallbladder is impaired by mucin hypersecretion, similar to what
occur with cholesterol gallstones. Calcium bilirubinate polymerizes,
most likely by a free radical mechanism, within a mucin matrix to
produce a highly insoluble polymer, thus producing a mature black
pigment gallstone
 Clinical symptoms
 Gallstones usually produce symptoms by causing inflammation
or obstruction following their migration into the cystic duct or
common bile duct.
 The most specific and characteristic symptom is biliary colic –
severe, steady pain or fullness in RUQ or epigastrium with
frequent radiation to interscapular area, right scapula or
shoulder.
 Biliary colic begins quite suddenly and may persist with severe
intensity for 30 min to 5 hr, subsiding gradually or rapidly.
 May be precipitated by eating a fatty meal, by consumption of
a large meal following a period of prolonged fasting, or by
eating a normal meal; it is frequently nocturnal.
 Nausea and vomiting frequently accompany episodes of biliary
pain.
Mechanisms of biliary colic development
 Clinical symptoms
 An episode of biliary pain persisting beyond 5 hrs raises
the suspicion of acute cholecystitis
 Fever or chills (rigors) with biliary pain imply a
complication (cholecystitis, pancreatitis or cholangitis)
 Yellowish color of the skin or scleras along with clay-
colored stools suggest mechanic jaundice.
 Diagnosis
 Ultrasonography: procedure of choice for detection of
stones.
Advantages:
 accurate identification of stones
 simultaneous scanning of gallbladder, liver, bile ducts, pancreas
 ‘real-time’ assessment of gallbladder volume, contractility
 stones as small as 2 mm may be detected

Criteria for ultrasonografic gallstone identification:

 Acoustic shadowing of opacities that are within the
gallbladder lumen
 Opacities change with the patient’s position
Ultrasound: gallbladder containing a single
large stone which casts an acoustic shadow
 Diagnosis
 Plain X-ray: detects gallstones containing sufficient calcium. May
also be of use in the diagnosis of emphysematous cholecystitis,
porcelain gallbladder, and gallstone ileus.
 CT - can help determine the type of gallstone, identify pathological
dilation of the extrahepatic bile ducts.
 Endoscopic retrograde cholangiopancreatography (ERCP) refers
to imaging the biliary ducts and pancreatic duct using a retrograde
approach through an endoscope. ERCP is both a diagnostic and a
therapeutic procedure for certain conditions
 Oral cholecystography: may be used to access the patency of the
cystic duct and gallbladder emptying function. Can also delineate
the size and number of gallstones and determine whether they are
calcified.
 Radioisotope scans: accurate identification of cystic duct
obstruction, simultaneous assessment of bile ducts. Indicated for
confirmation of acute cholecystitis.
Frontal X-ray of a
large gallstone
(white circle,
upper right) 
Axial CT image
demonstrates a large
gallstone (arrow) in
the gallbladder
ERCP demonstrates stones in the common bile duct
on the left radiograph, and cystic duct on the right
radiograph (arrows).
 Complications
 Acute cholecystitis
 Pericholecystitis
 Gallbladder hydrops
 Gallbladder empyema
 Perforation of gallbladder with biliary peritonitis
development
 Gallstone fistula
 Cholangitis
 Obstructive (mechanical) jaundice
 Pancreatitis
 Treatment
Medical therapy – Gallstone dissolution
Ursodeoxycholic acid (UDCA) decreases cholesterol
saturation, allows dispersion of cholesterol from stones by
physical-chemical means, retards cholesterol crystal
nucleation.
Indications for UDCA therapy:
a) Radiolucent stones ≤ 10 mm in diameter
b) Functioning gallbladder
c) Not more than 50% of gallbladder lumen filled with stones
Dose: 8-10 mg/kg/day for 6 – 24 months
 Treatment
Extracorporeal shock-wave lithotripsy
Uses a focused ultrasound beam, can fragment larger
stones. The fragmented stones can be passed through the
cystic duct and expelled into the common bile duct. The
fragments that remain behind in the gallbladder should be
treated with UDCA for dissolution.
Indications: radiolucent, solitary stone < 2 cm in well-
contrasting gallbladder.
 Treatment
Topical dissolution therapy involves insertion of a catheter
into the gallbladder under ultrasound guidance; stones are
dissolved using methyl terbutyl ether.
 Treatment
Surgical therapy
Laparoscopic cholecystectomy – is a minimal-access approach for the
removal of the gallbladder together with its stones. It is a procedure of choice,
“gold standard” for treating of symptomatic cholelitiasis.
Indications for urgent cholecystectomy: complications of gallstone disease.
Indications for routine cholecystectomy:
1.The presence of symptoms that are frequent enough or severe enough to
interfere with the patient’s general routine
2.The presence of a prior complication of gallstone disease
3.The presence of an underlying condition predisposing the patient to
increased risk of gallstone complications (calcified or porcelain gallbladder
and/or previous attack of acute cholecystitis regardless of current symptomatic
status)
4.Very large stones (>3 cm in diameter)
5.Patients having gallstones in congenitally anomalous gallbladder
 Chronic cholecystitis
Definition:
CC refers to inflammation of a gallbladder of bacterial
origin mainly, that occurs under presence of biliary
dyskinesia, gallstones, parasite infections.
 Etiology
1. Main causes for CC development:
Opportunistic pathogenic infections (E.coli, coccal flora),
sometimes – other microbial causes (Proteus,
Pseudomonas aeruginosa, etc.)
Bacteria can get to gallbladder by contact path from the
small intestine, or by hematogenic and lymphogenic
path from any site of chronic inflammation.
 Etiology
2. Additional causes:
 Hypotonic and atonic biliary dyskinesias with stagnation of bile
 Hypodynamia + unbalanced diet
 Pancreatic reflux
 Genetic factors
 Parasite infections
 Pathogenesis
Development of CC is gradual.
Entry of microbial flora against a background of GB
hypotonia causes catarrhal inflammation of mucosa.
Inflammation progresses to submucosa and muscular layer
of GB, where it causes infiltration and activation of
connective tissue. These processes lead to deformation of
GB and pericholecystitis development.
In case of different unfavourable circumstances CC may get
exacerbated up to acute cholecystitis.
 Clinical symptoms
 Pain in RUQ and epigastrium, can last for hours, increases
after fatty, fried, spicy food, eggs, wine, beer. Pain radiates
to right scapula or shoulder.
 Tenderness during palpation in right subcostal area
 Bitter taste in mouth in the morning
 Nausea
 Belching
 Bloating
 Bowel movement disorders – alternation of constipations
and diarrheas
 Subfebrile body temperature
 Diagnosis
Ultrasonographic criteria of inflammation in GB:
 Thickness of wall of GB > 4 mm in the absence of liver and
kidney pathology, heart failure.
 Increase of GB size over 5 cm above the normal for the
corresponding age
 Presence of sonographic Murphy's sign
 Presence of paracystic hypoechogenic limbus (edema of GB
wall)
 Diagnosis
Cholecystography
The following symptoms are characteristic for patients with
CC:
 Absence of GB shadow
 Derangements of concentration ability and motility of GB
(delayed emptying)
 Deformation of GB wall
 Diagnosis
Duodenal intubation
(conducted only if gallstones are absent!)
1.Helps to access motor function of GB
2.Provides 3 portions of bile for further studying of bile
characteristics:
 Microscopy – signs of inflammation and lithogenicity of bile
 Culture – determination of bacterial flora
 Biochemical analysis – determination of cholesterol, bile acids,
phospholipids in bile
 Treatment: phase of exacerbation
Antibiotics:
Ciprofloxacin 500 mg 2/d per os, course 5 days
Cefotaxime 1 g 2/d i/m
Doxycycline 100 mg 2/d per os, course 5 days
Amoxicillin 500 mg 3-4/d
Tinidazole 4 pills per os once (if Lamblia is a causative agent)

Indications for antibiotic therapy:

 presence of clinical and laboratory signs of inflammation
 positive results of bile culture
 cholangitis
 Treatment: phase of exacerbation
Symptomatic therapy:
1.Prokinetic agents – domperidone 10 mg 3/d 30 min prior
to meals
2.Spasmolytics:
 mebeverine 200 mg 2/d, course 3-4 weeks
 drotaverine (No-Spa) 40 mg 3/d before meals
 papaverine hydrochloride 2% - 2,0 i/m
3.Bile-expelling medications (cholagogues)
4.UDCA – 8-10 mg/kg/day (if microlites and/or stagnation
of bile are present)
5.Herbal hepatoprotectors with bile-expelling properties
 Treatment: phase of remission
 Diet – meals 5-6 times a day, exclude fatty, fried, spicy,
smoked food, pickles, alcohol.
 Phytotherapy
 Mineral water
 Physiotherapy
 Exercise therapy
 Treatment: cholagogues
1. Preparations that stimulate cholepoietic function of liver
(choleretics)
• Preparations of bile acids: cholenzym, liobilum
• Synthetic preparations: oxaphenamide, cyclovalone
• Preparations of herbal origin: strawflower extract, peppermint
extract, corn stigmas
• Preparations that improve secretion of bile by increasing of its
aqueous component (hydrocholeretics) – mineral waters
2. Preparations that stimulate biliary excretion:
• Cholekinetics (inrease tonus of GB and decrease tonus of bile
ducts): xylite, sorbite, magnesium sulfate
• Cholespasmolytics: anticholinergic drugs, aminophylline.