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Anatomy of the bile ducts
Bile Duct Diseases - Harvard Health
Anatomy and flow of bile. Sphincter of Oddi regulates bile flow. Liver secretes bile constantly, closed sphincter of Oddi ensures filling of gallbladder, open sphincter is followed by bile drainage from the gallbladder towards duodenum.
Bile duct obstruction causes biliary hypertension.
Reliability of biliary system – bile duct lumen of 1 mm is enough for daily bile passage.
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Anatomy of hepatic lobule
Substrates from sinusoid normally pass into the hepatocytes. After metabolic transformation, some metabolites (bile, bile acids, etc.) pass into the bile capillary. A part of metabolized substrates return to sinusoid and pass into systemic circulation.
1 – bile capillary
2 – layer of hepatocytes
3 – space of Disse
4 – sinusoid
5 – portal vein branch
6 – hepatic artery branch
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Definition: any impairment of secretion and release of bile from the hepatocyte to the major duodenal papilla is called cholestasis. Thus, this concept includes both biochemical and mechanical disorders.
Cholestasis is a universal liver reaction against any type of lesion (ischemic, toxic, obstructive, metabolic, autoimmune).
Types of cholestasis: extrahepatic (biliary hypertension, obstructive jaundice), intrahepatic, combined.
Cholestasis
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Cholemia
Homeostasis disorders: vascular dilatation, reduced peripheral vascular resistance and total blood volume, bradycardia, vagal effects, reduced renal glomerular filtration.
Dysfunction of RES (80% of cells in liver), Kupffer cells, inflammatory cytokine release (TNFα, IL6, IL8, etc.), endothelial dysfunction.
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Acholia
Acholia is followed by advanced bacterial colonization of bowel, release of toxins and their translocation into portal blood. One microbe decays to form 3 million molecules of lipopolysaccharide toxin (LPS).
Functional overload of Kupffer cells associated with cholemia and advanced flow of microbes and toxins causes their partial dysfunction that leads to translocation of bacteria and toxins into systemic circulation, development of systemic inflammatory response and multiple organ failure.
Jaundice is a universal liver response to adverse effects resulting dramatic changes in various systems.

Painful and painless obstructive jaundice
Various rates of biliary hypertension development (fast, sudden or slow, gradual) determine occurrence of painful or painless obstructive jaundice. Sudden biliary hypertension is followed by acute pain in the right upper abdominal quadrant. Slow progression of biliary hypertension determines painless jaundice. Fast development of biliary hypertension is mainly observed in cholangiolithiasis, a slow one – in patients with bile duct tumors.
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PAINFUL OBSTRUCTIVE JAUNDICE
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Cholangiolithiasis
Gallstone migration from the gallbladder.
Obstruction of common hepatic duct and common bile duct.
Obstruction of major duodenal papilla.
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Stenosis of major duodenal papilla
Causes: cholangitis, pancreatitis, instrumental injury, gallstone passage, parapapillary diverticulum, functional disorders of the sphincter of Oddi.
Morphological changes: fibrosclerotic disorders.
Symptoms: pain, intermittent jaundice, urine and stool discoloration.
Diagnosis: endoscopic examination of major duodenal papilla, ERCP, PTC, manometry.
Treatment: endoscopic or surgical intervention for severe stenosis.
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Choledocholithiasis. Ultrasound
Dilatation of the bile ducts, doubling of the tubular structure
Calculi in the bile ducts
Endoscopic ultrasound – small calculi
Sensitivity of ultrasound – 28-50%, endoscopic ultrasound– 98%.
а – ultrasound: common bile duct enlargement and calculus (arrow).
б – ultrasound: calculus inside the common bile duct (arrow).
в – endoscopic ultrasound: a small calculus is visualized (arrow).
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ERCP
ERCP – diagnosis of calculi (а, arrow), hepatic duct injury after laparoscopic surgery (б, arrow).
Sensitivity – 89-98%.
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PTC
Mirizzi syndrome. Hepatic duct calculi.
Sensitivity - 90-100%.
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MRCP. МR-cholangiography
Imaging of gallbladder, bile ducts and calculi (arrows) without contrast enhancement.
Sensitivity 85–88%.
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ERCP vs. MRCP
ERCP
A relatively invasive method requires contrast agent injection into the bile ducts, biliary hypertension and irradiation.
Calculi
Calculi
MRCP
Non-invasive method without the need for direct contrast enhancement of the bile ducts.
Less clear image, but no irradiation.
Images were obtained from the same patient. Calculi were removed via endoscopic approach.
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Mirizzi syndrome
Type I - narrowing of common hepatic duct caused by calculus-induced compression of Hartmann's pouch
Type II - fistula between the gallbladder and hepatic duct. Hypertension of lobar hepatic ducts
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Bile duct cysts. Classification
Todani classification
Cysts are diagnosed in patients aged 3 months - 16 years and often cause obstruction of the bile ducts
Hereditary disease
No muscle layer and collagen fibers. Liver fibrosis
Periductal eosinophilic infiltration
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Caroli disease (cystic lesion type V)
Surgery – liver resection
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Primary sclerosing cholangitis
Chronic course
Cause is unclear
Multiple strictures and dilatations of intrahepatic bile ducts
Outcome: liver cirrhosis, cholangiocarcinoma is rarer
Diagnosis: direct contrast enhanced methods, MRCP
Radical approach – liver transplantation
Idiopathic gallbladder obliteration, autoimmune disease, frequent combination with ulcerative colitis, Crohn's disease. Higher-than-normal levels of AST and ALP.
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Haemobilia
Damage to the liver or intrahepatic bile ducts, local liver necrosis. Haemobilia is a secondary sign of the underlying disease.
Right upper quadrant abdominal pain, melena, transient jaundice.
Endoscopic examination of major duodenal papilla, ERCP, angiography, ultrasound, CT, MRI
Mortality rate 32–50%.
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Parasitic invasion
Opisthorchiasis (Ob, Volga basin, East Asia)
Echinococcosis, alveococcosis, ascariasis, Fascioliasis– Fasciola gigantica
Schistosomiasis – tropical helminth
Parasites penetrate into the bile ducts from the duodenum
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Symptoms and diagnosis of painful obstructive jaundice
Acute onset
Scleral icterus
Pain attack
Dark urine, stool discoloration
Common previous cholelithiasis
Ultrasound, ERCP, PTC, MRCP, CT, endoscopic ultrasound.
Laboratory survey.
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ACUTE CHOLANGITIS
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Acute cholangitis (AC)
AC is an infectious inflammation of the bile ducts. Most often, AC develops on the background of obstructive jaundice and biliary hypertension. AC is associated with penetration of microbes (Escherichia coli, Klebsiella, Proteus) from the duodenum into the bile ducts.
Metabolic products of microbial cells cause acute biliary hypertension.
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Cholangiovenous reflux
Corrosion casting. Scanning electron microscopy
Secretory pressure. Microbial metabolite pressure. L., Pellegrini C.A., Way L.W. Am. J. Surg., 1988; 155: 23–28.
* Particle of 1,7 µm – is a size of microbe
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1 – bile capillary
2 – layer of hepatocytes
3 – space of Disse
4 – sinusoid
5 – portal vein branch
6 – hepatic artery branch

Symptoms of acute cholangitis
Chills, fever
Leukocytosis
Infection
Symptoms associated with biliary hypertension and obstructive jaundice
Recurrent systemic inflammatory response with organ dysfunction
Charcot's triad:
fever, rigors, jaundice
Reynolds’ pentad :
Charcot's triad +
altered mental status, hypotension
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Causes of short-term SIRS and symptoms of sepsis
Two factors:
Large purulent surface of gallbladder, direct biliovenous reflux - sinusoidal endotoxemia
Kupffer cell failure caused by cholemia - systemic endotoxemia, increased release of pro-inflammatory cytokines – systemic inflammatory response, sepsis.
The difference between cholangitis and other purulent diseases is high sinusoidal endotoxemia combined with Kupffer cell failure.
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Criteria of SIRS and sepsis
Body temperature > 38ºC or < 36ºC
Heart rate > 90 beats per minute
Tachypnea > 20 breaths per minute or PaCO2 < 32 mm Hg
Leukocyte count >12 000 or < 4000
SIRS = 2 criteria
SIRS + infection = sepsis
Consensus conference of ACCP and SCCM, 1991
Severe sepsis: oliguria <500 ml/day, encephalopathy
Septic shock: BP < 90 mm Hg or reduction by 40 mm Hg
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Organ dysfunction criteria
CVS – hypotension requiring dopamine support
CNS – impaired consciousness
Respiratory system – tachypnea >20 or PaСO2 < 32 mm Hg
Kidney – serum creatinine > 2,0
Liver – hypoalbuminemia, prothrombin index↓
Coagulation – platelets < 100 000
Severe systemic dysfunction – multiple organ failure
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Renal failure in acute cholangitis
Kidney is a main organ secreting bile components – cholemic nephropathy.
Cholemia and endotoxemia cause renin and aldosterone release, increased level of atrial natriuretic peptide, vasodilation, reducing total blood volume, renal and glomerular blood flow, arterial and venous thrombosis.
Renal failure is more common in patients with jaundice and cholangitis compared to those without jaundice.
The difference of cholangitis from other purulent diseases is high incidence of renal failure
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Management of acute cholangitis (choledocholithiasis, n = 613)
Objective: to interrupt the course of cholangitis, to prevent sepsis.
Main measures: decompression and antimicrobial therapy.
Minimally invasive techniques (ERCP, PTC) reduced morbidity and mortality.
Data of the Hepatobiliary Surgery Department
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Treatment of pyogenic liver abscesses in acute cholangitis (n = 19)
The main requirement is biliary decompression + puncture or drainage of the abscess.
Mean duration of acute cholangitis – 8 days. Solitary – 7, multiple – 2, miliary – 10. Symptoms are significantly determined by severity of cholangitis.
Percutaneous puncture (abscess volume – 15–120 ml):
≤80 ml – efficacy 80%, >80 ml – efficacy 33%
Percutaneous drainage (abscess volume 30–160 ml).
Volume < 120 ml – efficiency is 15 times higher than for volume > 120 ml.
Duration of drainage – 10–55 days.
Surgery: drainage, liver lobe resection – 3.
Miliary abscesses – antimicrobial therapy without surgery – 10, 4 patients died.
Severe sepsis – 5, 2 patients died.
Septic shock – 7, 4 patients died.
Risk factors: miliary abscesses, septic shock, inadequate drainage, high creatinine.
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Stages of acute cholangitis and Tokyo Guidelines (2007)
*Overall and antimicrobial therapy
Emergency biliary decompression is required for severe acute cholangitis (stage III)
In mild stages, it is important to determine response to therapy. Emergency biliary decompression is required if there is no response (moderate, stage II).
Antibiotics enter the bile only after medical or surgical decompression. An importance of decompression in emergency surgery.
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Chronic cholangitis
Chronic cholangitis may be diagnosed in patients with:
post-traumatic strictures;
primary sclerosing cholangitis;
Klatskin tumors with vascular lesion;
AIDS-associated cholangitis.
Long-term course
Persistent infection
Recurrent biliary obstruction
Secondary immune deficiency (impaired response of lymphocytes to concanavalin, reduced number of NK cells, CD4/CD8 <0.5)
Secondary biliary cirrhosis is common
Chronic cholangitis in post-traumatic stricture
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Chronic cholangitis in patients with AIDS
Causative agents : Cryptosporidium and Cytomegalovirus. Features: stenosis of major duodenal papilla and bile duct enlargement, thickened walls of common bile duct
(а, arrow) and gallbladder (б, arrow).
Symptoms: right upper quadrant abdominal pain and fever without jaundice and itching.
Diagnosis: ultrasound, ERCP, CT
Prognosis: life expectancy after manifestation of biliary symptoms – near 7 months
Nash J.A., Cohen S.A. Gastroenterol. Clin. N. Am. 1997; 26: 2
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Conclusion
Acute cholangitis is characterized by purulent process proceeding on the background of cholemia and acholia caused by obstructive jaundice. This determines the features of course in comparison with other purulent diseases.
Features of acute cholangitis:
Large purulent surface of gallbladder. Cholangiovenous reflux.
Advanced portal endotoxemia combined with cholemia-induced Kupffer cell failure. Systemic endotoxemia. Short-term SIRS and organ failure.
High incidence of renal failure.
Endoscopic methods ensure simultaneous diagnosis and treatment of acute cholangitis, early decompression of gallbladder in critically ill patients, and lithoextraction in 90% of patients. Endoscopic treatment reduces the risk of severe sepsis and septic shock, results low mortality and is currently preferable treatment strategy.
A distinctive feature of chronic cholangitis is recurrent gallbladder obstruction and secondary immune deficiency.
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PAINLESS OBSTRUCTIVE JAUNDICE
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Tumors of bile ducts
Progressive biliary obstruction. Jaundice is the first, but not an early symptom. Features of Klatskin tumor and pancreatic cancer.
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Symptoms of painless obstructive jaundice
Icteric sclera and skin
Itching
Dark urine and stool discoloration
No pain as a rule
Signs of tumor growth are sometimes observed: body mass loss, no appetite, weakness
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Cancer of hepatic and common bile ducts
Common hepatic duct
(Klatskin tumor)
56%
Common bile duct 44%
Obstructive jaundice following a small tumor
No metastases for a long time (nodular and papillary forms as a rule)
Proximal growth
Early local invasion
Early lymphogenous metastasizing
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Classification of hepatic duct cancer (Bismuth)
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MR-cholangiography in Klatskin tumor
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Pancreatic head cancer. MRCP
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Differential diagnosis of obstructive and parenchymatous jaundice
Patients with a painless obstructive jaundice do not notice anything for many days because severe symptoms are absent. Patients often admit to infectious disease departments with a diagnosis of hepatitis and undergo examination for a long time. Differential diagnosis is simple - DETECTION OF ENLARGED common bile duct during ultrasound or other surveys.
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Functional and morphological features of liver in painless obstructive jaundice
Increased levels of direct and indirect bilirubin and alkaline phosphatase. A slight increase in AST, ALT, LDH in some patients. No other biochemical disorders.
Reduced prothrombin, platelets, rare signs of mild encephalopathy in long-standing obstructive jaundice (over 3-4 weeks).
Hepatocyte proliferation is replaced by their wrinkling and degeneration after 2-3 days (foci, fields). After 4 - 5 weeks, hepatocyte dimensions are reduced by 30-40%, their volume decreases from 97% to 40%.
Bile duct proliferation from the first day. After 4–5 weeks, their volume is increased from 2% to 40%,volume of stroma - from 1% to 20%.
Phlebitis of portal vein branches, neutrophilic infiltration, increased permeability of intercellular junctions.
Wu P.C. et al. – J. Pathol. 1981,133: 61–74.
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Metabolic disorders in painless obstructive jaundice
Reduced ATP and local blood flow velocity are associated with long-standing obstructive jaundice and progressive hyperbilirubinemia (p <0.05)
HGF release - regeneration regulator (ATP interval 0.53-0.6 μmol/g of tissue) – the 9th day
TNF-α release - apoptosis factor (decrease in ATP below 0.365 μmol/g of tissue) - after the 12th day
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Conclusion on disorders arising in painless obstructive jaundice
Painless obstructive jaundice causes severe functional and morphological disorders in liver associated with biliary hypertension, cholestasis, cholemia and acholia.
These disturbances result extrahepatic disorders, microbial colonization of gastrointestinal tract, portal endotoxemia, RES dysfunction, especially Kupffer cells, systemic toxemia followed by organ dysfunction.
Intra- and extrahepatic disorders together with persistent obstructive jaundice and progressive hyperbilirubinemia acquire a critical nature (fragile stability state), and additional effect ("second impact") can result SIRS and multiple organ failure.
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PREOPERATIVE DECOMPRESSION
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Preoperative decompression of the bile ducts
Methods of preoperative biliary decompression:
Percutaneous cholangiostomy. Endoscopic nasobiliary drainage or stenting.
Cholecystostomy: open, ultrasound-assisted laparoscopic percutaneous.
Open choledocho- or hepaticostomy.
A fairly complete restoration of liver and other systems requires prolonged decompression of the bile ducts (3-4 weeks). Therefore, various stents are often used for this purpose. For short-term decompression, drainage tubes are used. The last ones may be later replaced with stents.
Secondary obstructive jaundice is often more dangerous for the patient's life than the underlying disease that caused this syndrome. Therefore, minimally invasive correction of obstructive jaundice is essential in some patients. These patients undergo a two-stage surgery: stage 1 – bile duct decompression, correction of hyperbilirubinemia, stage 2 – total resection of tumor.
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Can bile duct decompression per se impair liver function?
In a 12-day obstructive jaundice, decrease of ATP, progressive energy deficit of liver tissue and hyperbilirubinemia have been observed for 3 days. This the so-called post-decompression syndrome is probably associated with fast decompression of the bile ducts (similar to fast drainage of abdominal effusion).
ATP restoration after decompression in 6- and 12-day obstructive jaundice
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Comparison of various methods of bile duct decompression (n = 205)
NBD-85, PTC-37, cholecystostomy-63, CBD decompression -20
NBD – В = 4,6; PTC – В = 10; cholecystostomy– В = 9
NBD was followed by gradual decrease in biliary pressure throughout the entire period of decompression. An acceptable pressure was achieved by the 7th day. Other methods were characterized by faster decrease in biliary pressure. Decompression rate may be adjusted by raising or lowering the outer end of drainage tube.
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Morbidity and mortality in various rates of bile duct decompression
* – p < 0,05
Slow decompression rate is associated with fewer complications and no mortality
– fact decompression (PTC, CS)
– slow decompression (NBD)
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Positive and negative aspects of preoperative biliary decompression
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Opinions on stenting are still controversial. However, there are absolute indications for preoperative biliary decompression: cholangitis, neoadjuvant chemotherapy, inoperable tumor, risk of radical surgery.
Additional factors in favor of preoperative biliary decompression: serum bilirubin > 200 mmol / L and Klatskin tumor.

Features of preoperative biliary decompression in Klatskin tumor
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Radical surgery for Klatskin tumor implies extended liver resection. Future liver remnant (preferably at least 30%) must be functionally adequate that is facilitated by preoperative decompression of the bile ducts.
Percutaneous transhepatic selective drainage of segmental bile duct of future liver remnant is of particular importance. This procedure together with increased portal blood flow facilitate fast regeneration and enlargement of liver remnant.