Choledocholithiasis, acute cholangitis and gallstone ileus

• Choledocholithiasis is a stone in the common bile duct. Most are secondary (they have travelled from the gallbladder), but some form in the duct itself.
• A simple obstruction causes biliary colic, jaundice, dark urine, pale stool and itch, without fever. Fever, rigors and hypotension mean infection has been added: acute cholangitis.
• Acute cholangitis is therefore obstruction plus infection, and it ranges from mild to organ failure. The Tokyo Guidelines use Charcot triad for diagnosis and a three-grade severity scale to decide who needs urgent drainage.
• Stable patients with a suspected duct stone are risk-stratified by the ASGE 2019 criteria; high probability goes straight to ERCP, intermediate probability is confirmed by MRCP or endoscopic ultrasound, and low probability has duct clearance performed with the cholecystectomy.
• Gallstone ileus is the odd one out: a large stone erodes through a cholecystoenteric fistula and blocks the terminal ileum, mainly in older women; on imaging it gives Rigler triad.

By the end of this page you should be able to:

1. Explain the difference between biliary colic, choledocholithiasis without infection, and acute cholangitis.
2. Read a cholestatic liver panel and say what raised alkaline phosphatase, GGT and conjugated bilirubin mean.
3. Apply the 2019 ASGE risk stratification for common bile duct stones and choose between ultrasound, MRCP, endoscopic ultrasound, intraoperative cholangiography and ERCP.
4. Diagnose acute cholangitis with the Tokyo 2018 criteria, grade its severity, and name the antibiotics and drainage plan for each grade.
5. Describe the prevention of post-ERCP pancreatitis and the place of laparoscopic bile duct exploration.
6. Recognise gallstone ileus from its pathophysiology and from Rigler triad, and choose a surgical approach.
7. Outline what to do when MRCP, ERCP and advanced surgery are not available.

Secondary stones are travel stones. They are the ones that interrupt surgery and that cause acute biliary pancreatitis when they impact at the ampulla. Primary stones are usually brown pigment stones (calcium bilirubinate mixed with cholesterol) and they recur unless the underlying stasis or infection is corrected. Black pigment stones, by contrast, are usually associated with haemolysis and are less common in the duct.

Acute cholangitis is defined as bacterial infection of the biliary tree in the setting of obstruction. It is not simply "infected bile": it is obstruction plus infection, and the obstruction is what turns a localised infection into a septic emergency. Choledocholithiasis is the commonest cause, but strictures, tumours, prior ERCP and stents, and primary sclerosing cholangitis can all produce the same clinical picture.

Gallstone ileus is mechanical small-bowel obstruction caused by a gallstone that has entered the gut through a fistula between the gallbladder and the bowel, usually the duodenum. The stone is almost always large, and the obstruction is most often in the terminal ileum, which has the narrowest diameter.

Mirizzi syndrome is a related but distinct problem: a stone impacted in the cystic duct or in Hartmann pouch compresses the adjacent common hepatic duct from outside, producing jaundice that looks like a common duct stone.

Up to 10 to 20% of people with symptomatic gallstones have a concomitant common bile duct stone at the time of their work-up. ^[1] Not all of these cause trouble: some are silent, others declare themselves with biliary colic, jaundice or pancreatitis.

Acute cholangitis is one of the serious complications of biliary obstruction. The mortality of biliary infection in general is 1 to 6%, but it rises to 10 to 20% when bacteraemia is present. ^[2] Bloodstream infection is present in 25 to 75% of patients with acute cholangitis. ^[2]

Gallstone ileus is rare. It accounts for 1 to 4% of all small-bowel obstructions, and for about a quarter of obstructions in people over 65 years. ^[4] It affects women about 3.5 times as often as men and is a disease of older adults. ^[4]

Common bile duct stones share the risk factors of gallstones: increasing age, female sex, obesity and rapid weight loss, pregnancy and possibly genetic factors. Stones become more likely to enter the duct once the gallbladder is stone-laden and once biliary dynamics are disturbed.

Acute cholangitis arises when obstruction and infection coincide. The organisms are the ordinary flora of the bowel, because the biliary tree and the gut share drainage through the ampulla of Vater. Common causes of obstruction other than gallstones include biliary strictures, malignant obstruction, primary sclerosing cholangitis, post-ERCP or post-surgical change and complicated cholecystitis. Infection of the biliary tree after ERCP is an increasingly important cause, especially where stents are present, because the flora of a stented duct differs from that of a native duct.

Gallstone ileus requires three things: a large stone, chronic inflammation that erodes the gallbladder wall into an adjacent loop of bowel, and (usually) obstruction of the distal biliary tree that raises pressure inside the gallbladder and drives the erosion. A cholecystoduodenal fistula is the usual connection.

Choledocholithiasis. A stone in the duct raises intraductal pressure. If it is completely obstructing, bile cannot drain, pressure rises behind the stone and the patient develops jaundice and cholestatic liver chemistry. If it is partially obstructing or briefly stuck, the patient has pain but little jaundice. Stasis behind the stone favours bacterial overgrowth, and bacteria in an obstructed system cannot be cleared by the normal flow of bile; infection follows. Reflux of bile and bacteria down the common channel into the pancreatic duct is the mechanism of gallstone pancreatitis.

Acute cholangitis. The initial event is bacteraemia from the pressurised, infected biliary tree. Bacteria and their products cross into the circulation when duct pressure exceeds the pressure in the surrounding vessels, producing sepsis. Systemic inflammation then unmasks organ dysfunction: the liver (coagulopathy), kidneys, lungs and brain. This is why a patient can look well at 8 a.m. and be in shock by noon.

Gallstone ileus. Once a large stone has entered the bowel, it is carried distally until it reaches a segment narrow enough to trap it. The terminal ileum is the commonest site, in about 60% of cases, followed by the jejunum. ^[4] The stone has to be larger than about 2 cm before obstruction is likely. ^[4] The obstruction is therefore mechanical and high-grade, with vomiting, distension and absent flatus; it is not an ileus in the physiological sense.

Ask in the patient's own words. Patients with choledocholithiasis describe a steady or colicky pain in the epigastrium or right upper quadrant, often radiating to the back or to the scapula. It is usually not relieved by antacids. Nausea and vomiting are common; fever and rigors are not expected, and when they occur the diagnosis has shifted to cholangitis.

Jaundice may be noticed as yellowing of the sclerae or skin. Patients often report dark, tea-coloured urine and pale, clay-coloured stool, sometimes days before anyone looks at the eyes. Itching (pruritus) is common, worse at night and after a warm bath, because bile salts deposit in the skin. Appetite falls; weight loss may follow. Attacks can be short-lived if the stone drops back into the duct or passes into the duodenum, so a pain-free patient with jaundice still needs the same work-up.

Acute cholangitis adds fever and rigors to the picture. The classic triad of right upper quadrant pain, jaundice and fever (Charcot triad) is specific but is seen in only 20 to 50% of patients. ^[2] Its sensitivity is between 21 and 26%. ^[2] The more reliable marker of severe disease is the Reynolds pentad: Charcot triad plus shock and confusion, two signs of organ failure. ^[2]

Gallstone ileus presents in an older patient after a short history of pain, vomiting and abdominal distension, with absolute constipation or minimal flatus. The diagnosis should be considered whenever an older woman has small-bowel obstruction with no prior abdominal surgery: there are no adhesions to explain it.

Look for jaundice in daylight. Palpate the right upper quadrant for tenderness; in uncomplicated choledocholithiasis there is no guarding or rebound. Undue tenderness, a rigid abdomen or systemic illness suggests cholecystitis, cholangitis or perforation. A palpable gallbladder is not a feature of simple duct stones in adults with chronic disease; an enlarged, palpable gallbladder in a jaundiced patient suggests malignant obstruction.

Fever is the pointer to infection. Rigors are common in cholangitis. Tachycardia, tachypnoea and hypotension define sepsis and need a resuscitation bundle immediately.

Murphy sign is negative in choledocholithiasis unless acute cholecystitis coexists. Scratch marks and excoriations betray pruritus. Kinking of the conjunctivae from jaundice is useful in pigmented skin. A sudden change in mental state in an elderly jaundiced patient is an emergency: it may be septic encephalopathy or hypoglycaemia, not simply "old age".

First-line for every patient

• Full blood count and C-reactive protein, to look for leucocytosis or an inflammatory response.
• Liver panel: bilirubin (total and direct), alkaline phosphatase, GGT, and the transaminases. A cholestatic pattern (raised alkaline phosphatase, GGT and conjugated bilirubin) argues for obstruction; a modest transient rise in ALT and AST is common during an attack and does not by itself mean hepatitis. ^[1]
• Amylase and lipase, to exclude gallstone pancreatitis.
• Renal function and glucose, especially before contrast imaging or ERCP.
• Blood cultures before antibiotics if cholangitis is suspected.
• Transabdominal ultrasound: look for stones in the gallbladder, for dilatation of the common bile duct, and, if seen, for a stone in the duct itself. Ultrasound is highly specific but has a low sensitivity, 42 to 63%, for the ducts themselves. ^[2] A normal ultrasound does not exclude a duct stone, particularly in the distal duct, which is often hidden by bowel gas.

Confirmatory tests

• MRCP is the standard non-invasive test for the ducts. Its sensitivity for bile duct stones is greater than 90%, but stones smaller than 6 mm can be missed. ^[2] It is the test of choice in jaundice and when the ultrasound is equivocal.
• Endoscopic ultrasound has comparable accuracy to MRCP for stones and may be more sensitive for small stones; it is operator-dependent and, when sedation requires anaesthesia, more costly. The 2019 ASGE guideline considers either EUS or MRCP acceptable in patients at intermediate probability of a duct stone, choosing by local availability and patient factors. ^[1]
• Intraoperative cholangiography or intraoperative ultrasound can be used during laparoscopic cholecystectomy to clear the question at surgery; many surgeons prefer this to preoperative duct imaging when probability is intermediate.
• ERCP is primarily a treatment, not a diagnostic test. It should be reserved for patients with high probability, for patients who also need biliary drainage, or for centres without MRCP or EUS.
• CT abdomen is poor at showing small non-calcified stones, but it is excellent for gallstone ileus, for Mirizzi syndrome, for collections or abscess, and for staging suspected malignancy. The plain abdominal film may show only the small minority of stones that are calcified, but it sometimes shows pneumobilia or an ectopic stone.
• Bile duct diameter on imaging: greater than 6 mm in adults with an intact gallbladder, or greater than 8 mm after cholecystectomy, counts as dilated in this context. ^[1]

Acute cholangitis is diagnosed clinically, because no single test confirms it. The 2018 Tokyo Guidelines give a composite set of criteria based on systemic inflammation, cholestasis and imaging. ^[2]

A suspected diagnosis requires one criterion from A plus one from B or C. A definitive diagnosis requires one from A, one from B and one from C. ^[2] The tool has a diagnostic accuracy of about 90%, although its specificity has not been formally assessed. ^[2]

These criteria deliberately lean heavily on imaging and on liver chemistry, because blood tests alone cannot separate infection from simple obstruction. In an older or immunosuppressed patient the inflammatory criteria may be blunted, and the diagnosis has to be made earlier and on softer evidence.

Severity is graded by organ function and by inflammatory markers, because the grade determines the speed of intervention and the level of care. ^[2]

Blood cultures are positive in 25 to 75% of patients with acute cholangitis, and infection is polymicrobial in up to 80% of cases. ^[2] Bacteraemia is present in about half. Enterococci are often present (up to about a third of isolates in some series) and anaerobes in up to 50%; anaerobes matter particularly when an anastomosis or stent is present. ^[2]

The common causative organisms are Escherichia coli, Klebsiella species, Enterococcus species, and anaerobes such as Bacteroides. ^[2] Their relative proportions vary between community-acquired and healthcare-associated infection, and between native ducts and stented ducts, which is why local antibiograms should be consulted.

Acute cholangitis is sepsis until proven otherwise. The first hour belongs to resuscitation and to source control:

1. Oxygen, intravenous access, a fluid challenge and repeated assessment of perfusion and urine output.
2. Analgesia and an antiemetic.
3. Fasting and nasogastric drainage if vomiting is significant.
4. Blood cultures and a full set of bloods before antibiotics where the patient can be stabilised for a few minutes.
5. Risk stratification for common bile duct stones if gallstones are known or suspected.

For mild grade I disease, antimicrobial therapy is often enough for the first 24 hours, but clinical reassessment must be frequent and the drainage team should be alerted early if there is no improvement.

Empirical therapy should cover enteric Gram-negative organisms and, in severe or healthcare-associated infection, enterococci, anaerobes and (where relevant) Pseudomonas. ^[2] The following examples are representative, not exhaustive; local resistance patterns dominate the choice. ^[2]

• Community-acquired, non-severe disease: a third-generation cephalosporin (cefotaxime or ceftriaxone), with an anaerobic agent added if there is a history of bilio-enteric anastomosis. ^[2]
• Severe disease, nosocomial infection, biliary stent or immunosuppression: a broad-spectrum cephalosporin such as cefepime, or piperacillin with tazobactam, together with anaerobic cover (metronidazole) and enterococcal cover (for example vancomycin) when an anastomosis is involved. ^[2]
• Empirical treatment combined with initial resuscitative measures is effective in 74 to 85% of cases, allowing biliary decompression to be deferred by 48 to 72 hours when the patient is improving. ^[2]

The standard duration is 4 to 7 days after successful biliary drainage, extended to two weeks where the organism is an Enterococcus or Streptococcus species, to reduce the risk of endocarditis. ^[2] Sepsis should trigger the Surviving Sepsis bundle: lactate, blood cultures, crystalloids, broad-spectrum antibiotics and vasopressors if needed.

This is the step that saves lives. Endoscopic drainage is preferred to surgical or percutaneous decompression, because the latter carry substantially higher morbidity and mortality in this setting. ^[2]

• Grade I (mild): drainage may be deferred while antibiotics work. Drain if there is no response within 24 hours, or if the bilirubin or fever does not fall. ^[2]
• Grade II (moderate): ERCP for drainage within 48 hours is commonly quoted, that is 24 to 48 hours, and should be organised without waiting for full stabilisation. ^[5] Earlier is better where the patient is unstable. ^[5]
• Grade III (severe): biliary drainage is an emergency, performed alongside organ support and resuscitation. Drainage within 6 hours is appropriate when there is haemodynamic instability or septic shock, and ERCP within 24 hours is associated with a 20% reduction in mortality compared with drainage after 24 hours. ^[2]
• If ERCP fails or is unavailable: percutaneous transhepatic drainage (PTBD) is the usual second line. Surgical drainage is a last resort, reserved for centres without endoscopic or percutaneous access, because emergency surgery in this context carries operative morbidity of up to 91% and mortality of up to 55%. ^[2]
• A temporary nasobiliary drain or biliary stent may be safer in a critically ill patient than a long procedure.

The flowchart below pulls the duct-stone and drainage arms together.

ERCP with sphincterotomy and stone extraction is the standard definitive endoscopic treatment of choledocholithiasis. The duodenoscope is advanced to the papilla of Vater, the bile duct is cannulated, and the ampulla is divided (sphincterotomy) to allow stones to be extracted with a basket or balloon. For large or difficult stones, endoscopic papillary large balloon dilatation after sphincterotomy improves clearance and reduces the need for mechanical lithotripsy. ^[1] Intraductal therapy (electrohydraulic or laser) is an alternative in specialist centres.

Stenting has two roles: temporary drainage when a stone cannot be extracted completely at the first session, and decompression in sepsis. Do not leave an asymptomatic patient with an indwelling stent and no plan for retrieval.

Prevention of post-ERCP pancreatitis, the commonest serious complication, combines technique and pharmacology:

• Rectal non-steroidal anti-inflammatory drugs (indomethacin or diclofenac, 100 mg) around the time of the procedure reduce the incidence of post-ERCP pancreatitis in high-risk patients by roughly half, and their use has expanded to most patients without contraindication. ^[3]
• Timing in current practice is usually 30 minutes before or during the procedure. ^[3]
• Prophylactic pancreatic stents are used in selected high-risk situations, for example difficult cannulation or the double-guidewire technique. ^[3]
• Intravenous lactated Ringer solution with aggressive hydration is widely used, although its added benefit over NSAIDs alone is still debated. ^[3]
• Bleeding and perforation are uncommon but follow sphincterotomy and guidewire manipulation, and occur in separate percentages of the 0.9 to 6% "other adverse event" rate reported with ERCP. ^[1]

Baseline ERCP and bile duct stone clearance are not risk-free: 6 to 15% of patients suffer a major adverse event. ^[1] Post-ERCP pancreatitis alone occurs in 9.7 to 14.7% of patients in published series, and haemorrhage, perforation and cholangitis together in 0.9 to 6%. ^[1]

Single-stage treatment - laparoscopic cholecystectomy combined with laparoscopic common bile duct exploration - is attractive because it treats the cause and the consequence in one anaesthetic. Clearance is confirmed with a choledochoscope inserted through the cystic duct or through a choledochotomy, and a stone basket or balloon. The duct is usually closed over a stent or T-tube if a choledochotomy has been made, or primarily if the opening is small and the duct is healthy. This approach suits patients in whom cholecystectomy is already indicated and in whom duct stones are strongly suspected.

The trade-offs are well rehearsed: it avoids a separate ERCP, but requires surgical expertise, longer operating time and carefully chosen patients. Two-stage treatment (ERCP first, then cholecystectomy) is easier to organise in most hospitals and is the norm where biliary endoscopy is available. Neither strategy has been shown to be clearly safer for the patient.

Surgery is needed when ERCP fails, when there is a Mirizzi syndrome with fistula formation, or for gallstone ileus. A stone that cannot be extracted endoscopically, an impacted stone at the hilum or a tight stricture may force open clearance. For Mirizzi syndrome the cure is cholecystectomy; types with a cholecystocholedochal fistula may require biliary reconstruction by a specialist team.

Gallstone ileus requires laparotomy or laparoscopic surgery. The options are enterolithotomy alone, or enterolithotomy with cholecystectomy and fistula closure. Combined enterolithotomy plus cholecystectomy is associated with lower mortality than enterolithotomy alone (odds ratio 2.39 versus 3.09 for enterolithotomy alone in the quoted comparison), but the one-stage procedure is reserved for patients whose general condition is good and whose anatomy is favourable. ^[4] Enterolithotomy alone remains the mainstay and is the safer choice in a frail patient; definitive biliary surgery can be staged. ^[4]

Of choledocholithiasis itself:

• Acute (gallstone) pancreatitis, which is the commonest serious complication of duct stones and can be fatal at either end of the severity spectrum.
• Acute cholangitis and, if untreated, septic shock, liver abscess, portal pylephlebitis and secondary biliary cirrhosis with portal hypertension.
• Worsening cholestasis with fat-soluble vitamin deficiency and coagulopathy.

Of ERCP, see above. Minor bleeding from the sphincterotomy site is common and clinically significant haemorrhage usually declares within days. Perforation may be retroperitoneal (ampullary) and delayed in presentation.

Of gallstone ileus: high-grade obstruction with vomiting, dehydration, strangulation and, in older patients, a substantial risk of death even with surgery. Preoperative CT should not be delayed, because incomplete Rigler triad is common when the scan is limited.

With clearance of the duct and cholecystectomy, the prognosis is excellent. Recurrent common bile duct stones occur in a minority, mainly after incomplete clearance or where biliary stasis persists. Biliary infection mortality fell dramatically with antibiotics plus drainage, but it is still appreciable when drainage is delayed. Invasive cholangitis with bacteraemia carries a mortality of 10 to 20%. ^[2]

There is no population screening for common bile duct stones. Prevention is structural:

• Remove the gallbladder and clear the duct in symptomatic gallstone disease, ideally during the same admission for mild acute biliary pancreatitis. ^[5]
• Correct biliary strictures and eliminate parasites where relevant.
• Avoid unnecessary or low-value ERCP by using risk stratification and MRCP or EUS in intermediate-probability patients. ^[1]
• In an elderly or frail patient who cannot undergo cholecystectomy, a protective sphincterotomy reduces later biliary events, although it is not without risk. ^[5]

Pregnancy. Minimise radiation and invasive procedures. Ultrasound is the first test; MRCP without gadolinium can be used. ERCP is reserved for clear therapeutic need (cholangitis, severe jaundice, stones that will not pass) and is performed by an experienced endoscopist with fetal shielding. Surgical timing follows obstetric and surgical senior advice.

Older adults. Fever may be low-grade or absent, the pain may be vague, and mental confusion is often the first sign of sepsis. Gallstone ileus is a disease of older women, and delay in diagnosis is common. Co-morbidity, not the stone, usually determines outcome.

Children. Common bile duct stones are rare and usually secondary to a haemolytic state, a congenital duct anomaly or a parasite. Imaging with ultrasound and MRCP is preferred; ERCP for therapy only.

Frail patients. Consider sphincterotomy alone rather than combined endoscopic and surgical procedures, balancing the risk of recurrent biliary events against the higher mortality of surgery in this group. ^[5]

• Risk stratification can be done without MRCP or EUS. Use the simple ASGE bedside criteria (stones on ultrasound, clinical cholangitis, or bilirubin over 4 mg/dL with a dilated duct), together with the cholestatic liver tests. If none of the high-risk criteria are present, treat as suspected and refer rather than rush to unavailable endoscopy. ^[1]
• Ultrasound is the key test. Learn to measure the common bile duct and to look for stones, dilatation and gallbladder wall thickening. CT is often unavailable for biliary detail, but it is the test that makes gallstone ileus obvious.
• Blood cultures and MRCP are luxuries. Send cultures when they are possible, but do not delay antibiotics or drainage to obtain them.
• Antibiotics must at least cover enteric Gram-negatives. Third-generation cephalosporins, or amoxicillin-clavulanate where staphylococcal or anaerobic cover is needed, are reasonable empirical choices; add metronidazole for anastomoses or severe disease. ^[2]
• Drainage saves lives even without ERCP. If endoscopy is unavailable, percutaneous transhepatic drainage or an early surgical drainage (T-tube) should be used, with referral arranged as soon as possible. Septic shock demands action within hours.
• Cholecystectomy after recovery is the definitive prevention of recurrence. Where elective surgery is delayed, a protective sphincterotomy may bridge the gap, but it requires endoscopic capability.
• Gallstone ileus needs early surgical consultation. Enterolithotomy alone controls the emergency and can be followed by interval cholecystectomy if the patient is not fit for a one-stage operation.

• Choledocholithiasis is usually secondary (stone migrated from the gallbladder); primary stones form in the duct with stasis or infection.
• Biliary colic, uncomplicated duct stones and acute cholangitis are points on a spectrum from simple obstruction to obstruction plus infection.
• Uncomplicated choledocholithiasis causes cholestatic jaundice with raised alkaline phosphatase, GGT and conjugated bilirubin and sometimes a transient ALT rise; it is afebrile unless infected.
• In acute cholangitis the Charcot triad is specific but present in only 20 to 50% of patients (sensitivity 21 to 26%); the Reynolds pentad marks septic shock and confusion.
• Tokyo 2018 criteria diagnose acute cholangitis by combining systemic inflammation, cholestasis and imaging; severity is grade I, II or III.
• Common organisms are Escherichia coli, Klebsiella, Enterococcus and anaerobes such as Bacteroides.
• ASGE 2019 risk stratifies duct stones as high, intermediate or low; high probability goes straight to ERCP.
• MRCP sensitivity for duct stones is over 90%, but stones smaller than 6 mm can be missed.
• ERCP carries a 6 to 15% risk of major adverse events; post-ERCP pancreatitis occurs in 9.7 to 14.7% of patients.
• Rectal indomethacin or diclofenac 100 mg, given around ERCP, halves post-ERCP pancreatitis in high-risk patients.
• Biliary drainage is urgent in moderate disease (within 48 hours) and emergency in severe disease, with percutaneous drainage if ERCP fails.
• Gallstone ileus is a large stone through a cholecystoenteric fistula, usually obstructing the terminal ileum; Rigler triad (pneumobilia, small-bowel obstruction, ectopic stone) is seen in only 30 to 35% on plain film but CT is highly sensitive and specific.
• Emergency biliary infection without drainage carries a mortality of 1 to 6%, rising to 10 to 20% with bacteraemia.

Gastroenterology: gallstones and biliary colic; acute cholecystitis; acute pancreatitis; primary sclerosing cholangitis; primary biliary cholangitis; cirrhosis and portal hypertension; jaundice approach; acute abdomen; small-bowel obstruction; peptic ulcer disease. Future MedGrasp pages on gallstone disease, cholecystectomy and ERCP will complete the pathway.