Thursday, April 17, 2008


Management of Cholangitis

  • The term cholangitis refers to inflammation of the bile ducts within the liver, and the condition can be caused by many different factors including
  • ischemia,
  • infection, and
  • chemicals.
  • However, bacterial infection of the biliary tree complicating ductal obstruction is the most common cause of this entity.
  • Histologic evaluation of the liver reveals an abundance of polymorphonuclear leukocytes that are mainly distributed in the portal triads and often spill out of the ducts.
  • However, the mere presence of bacteria within the biliary tree does not in itself lead to cholangitis.
  • Partial or complete obstruction is an important coexisting factor, and the presence of high ductal pressures is thought to be important to the pathophysiology of this disease.

Previously, terms such as acute suppurative cholangitis and acute nonsuppurative cholangitis were coined. However, it appears that dividing the disease into these different groups is not helpful; patients with pus in their ducts can have a relatively indolent course, whereas those without pus can be profoundly ill.

Hence, we believe that only the term toxic cholangitis, referring to patients with hypotension and systemic illness, is a useful term because it describes a more severe form of the illness.


The two essential components that lead to acute cholangitis are

(1) the presence of bacteria in the biliary system and

(2) obstruction of the bile ducts with increased intraluminal pressure.

  • Although bile is normally sterile, 15% of patients undergoing cholecystectomy have bacteria isolated from the gallbladder lumen.
  • When obstructing stones are present, the incidence of bactobilia increases to 90%.
  • In addition, the incidence of biliary infection appears to be greater in patients
  1. who are more than 60 years old,
  2. in those with a history of liver disease and jaundice,
  3. and in those with a prior history of biliary disease, especially if these patients have undergone biliary bypass.

The four potential sources of bacteria in bile are

(1) the hepatic artery,

(2) the portal vein,

(3) lymphatic flow, and

(4) ascending infection through the bile duct itself.

The hepatic artery appears to be an unlikely candidate because an intravascular source of infection would be necessary if this were the case, and only approximately 30% of patients with acute cholangitis have positive blood cultures.

The portal vein has been viewed as the likely source of bacteria in cholangitis.

  • Studies demonstrate that as many as 32% of human portal vein blood samples have positive cultures for bacteria even when peripheral blood cultures are negative.
  • These data suggest that the liver is important in filtering bacteria that emanate from the bowel.
  • In addition, bacteria cultured from bile of patients with cholangitis are of gut origin, a finding supporting the portal vein as at least one source of bacteria.

Lymphatic channels are rich in the area of the portal triad. However, when lymph nodes are injected in the portal area, the dye tracts preferentially toward the duodenum, and this suggests that lymph flows away from the bile duct.

The ampulla of Vater provides a natural defense against reflux of gastrointestinal contents into the biliary tree.

  • Sphincterotomy or biliary-enteric bypass results in free reflux of gut contents into the bile duct that potentially contaminate bile.
  • However, clinical experience argues against the concept that this mechanism alone is a major source of biliary infection because few of these patients present with cholangitis.

Bacteria in the bile duct are rapidly cleared with normal bile flow.

  • Bactobilia is common with partial obstruction of the biliary tract and impaired drainage.
  • Sixty-four per cent of patients with partial obstruction have positive bile cultures.
  • With complete obstruction, bactobilia is less common (10% of patients), probably because ascending infection is not possible.
  • Patients with free reflux of intestinal contents into the bile ducts (i.e., after sphincterotomy) rarely develop cholangitis.
  • However, with partial bile duct obstruction, they frequently develop episodes of acute cholangitis.
  • Flemma et al. demonstrated that increased intraluminal pressure is required for development of cholangitis; bacteria even in excess of 10 organisms/ml of bile do not cause cholangitis unless the bile duct pressure is raised to greater than 25 cm of water.
  • Continued contamination of bile by reflux of intestinal contents may also overwhelm the normal hepatic mechanisms of bacterial clearance.
  • Bile salts themselves are bactericidal, and the liver contains the largest load of macrophages in the body.
  • The liver rapidly clears bacteria, especially if they are delivered through the portal vein, because Kupffer's cells ingest these organisms effectively.
  • Large bacterial loads may overwhelm these mechanisms and may allow bacteria to spill into bile. When this condition is combined with biliary obstruction and poor clearance of bacteria from bile, patients develop cholangitis.

Acute cholangitis also occurs without increased ductal pressure when the biliary epithelium is damaged, especially if bile is already colonized with bacteria.

  • Thus, patients undergoing invasive procedures on the biliary tree (e.g., cholangiography, placement of a biliary drain or stent by endoscopic retrograde cholangiopancreatography [ERCP] or percutaneous transhepatic cholangiography [PTC]) are at high risk of developing of acute cholangitis.
  • Iatrogenic episodes of acute cholangitis can be avoided by giving prophylactic antibiotics before the procedure.


The causes of acute cholangitis have changed in recent years.

  • Stone disease is less often a cause, whereas strictures, either benign or malignant, have become more common causes.
  • Reports in the literature are increasingly from tertiary hospitals treating patients with more complex malignant obstructions as opposed to stone disease.
  • Pitt's group treated more patients with cholangitis resulting from malignant strictures (57 of 96 patients) than resulting from stone disease (28 of 96 patients) from 1986 to 1989.


  • Gallstones have decreased as a cause of cholangitis.
  • Our belief is that the aggressive use of cholecystectomy for symptomatic cholelithiasis, especially since laparoscopic cholecystectomy was introduced, has decreased the incidence of the complications of stone disease.

Benign Bile Duct Strictures

  • Most benign biliary strictures develop after biliary bypass surgery.
  • They may occur years after the procedure.
  • Other causes include ischemia, possibly from hepatic artery injury.
  • Ischemic strictures have also been reported after continuous hepatic artery infusion chemotherapy for liver tumors.
  • Primary sclerosing cholangitis, an immune-based disease, results in stricture formation and is often associated with inflammatory bowel disease.
  • Acute episodes of infection frequently develop behind bile duct strictures caused by primary sclerosing cholangitis.
  • Patients with ulcerative colitis frequently have positive portal vein blood cultures and are at increased risk of acute cholangitis if they have biliary strictures.
  • Chronic pancreatitis can cause distal bile duct stricture.
  • Congenital conditions, such as choledochal cysts, cause bile stasis and biliary infection.
  1. The intrahepatic form of this disease is especially prevalent in Asia and bears the name Oriental cholangiopathy.
  2. Patients develop intraductal stones, bile duct strictures, and intermittent episodes of acute cholangitis.
  • Other rare causes of acute cholangitis include cavernous transformation of the portal vein that results in extrinsic compression and obstruction of the common bile duct and obstruction of the bile duct by parasites such as Ascaris.

Malignant Bile Duct Strictures

  • Tumors in the head of the pancreas, ampullary tumors, or biliary tumors eventually cause bile duct obstruction and may lead to cholangitis.
  • Although malignant strictures can cause acute cholangitis, most patients with malignant obstruction of the bile ducts present with jaundice because, as discussed earlier, complete bile duct obstruction is less likely to lead to cholangitis.

Parasites and Human Immunodeficiency Virus

  • Parasitic infection with Clonorchis sinensis or Ascaris lumbricoides can cause bile duct obstruction.
  • Parasites may fill the duct lumen directly and may thereby cause obstruction, or they may induce ductal fibrosis and stricture formation by attaching themselves to the biliary epithelium.
  • Parasites are common causes of acute cholangitis in the Far East, but they are rarely seen in the United States, except in immigrants and in persons with a history of recent travel to an endemic area.

Evidence shows that infection with human immunodeficiency virus (HIV) leads to a certain type of biliary obstruction that can cause cholangitis.

  • Specifically, these bile duct strictures resemble those observed in primary sclerosing cholangitis.
  • Alternatively, papillary stenosis with common bile duct obstruction is found in persons with HIV infection.
  • The organisms commonly found in the bile of these patients include cytomegalovirus and Cryptosporidium, and these pathogens need to be considered when one treats patients with HIV-related cholangitis.


  • Ninety to 100% of patients with acute cholangitis have aerobic bacteria in their bile.
  • The organisms are the same as those found in patients with colonized bile trees who do not have cholangitis.
  • These include the gram-negative bacteria Escherichia coli, Klebsiella, Proteus, and Pseudomonas species and gram-positive organisms, mainly Enterococcus and Enterobacter species.
  • Anaerobic bacteria are isolated in only 10% of cases, but this finding may be related to the stringency of the culture conditions: as many as 50% of bile cultures may harbor anaerobic bacteria, especially Bacteroides and Clostridium species.
  • Candida species have also been found in 18% of patients with biliary disease.
  • Morris et al. noted that fungus is more prevalent in patients with acute cholangitis as a result of malignant obstruction and in those who are immunocompromised, who have diabetes, or who have had a recent course of antibiotics.
  • Moreover, only 40% of patients with acute cholangitis have only a single organism isolated from their bile.


Most patients with choledocholithiasis or bile duct stricture present with abdominal pain, jaundice, elevated liver function tests, or gallstone pancreatitis, and they do not have infectious complications from bile duct obstruction.

  • However, every patient with bile duct obstruction is at risk of biliary infection if the obstruction is not relieved promptly.
  • When symptoms of bile duct obstruction are recognized early, the cause of the obstruction is determined, and the problem is addressed, infectious complications are avoided.

The classic presentation of acute cholangitisabdominal pain, fever, and jaundice—is termed Charcot's triad.

  • The presence of all three findings is highly specific for the disease, but it occurs in fewer than 60% of patients with acute cholangitis.
  • Therefore, Charcot's triad is frequently absent and does not correlate with the severity of the episode.
  • Reynolds and Dargan noted that septic patients presented with confusion and hypotension in addition to pain, fever, and jaundice.
  • Reynolds' pentad is characteristic of and specific for acute toxic cholangitis, but again, all five signs are frequently not present even in the sickest patients.
  • A diagnosis of acute cholangitis can be reliably established on clinical criteria alone if patients present with Charcot's triad or Reynolds' pentad.
  • The diagnosis is less clear in the absence of one or more of the signs.

As expected with a bacterial illness, fever is the most consistent sign in patients with acute cholangitis.

  • More than 90% of patients have a history of fever or chills, although fewer patients actually have fever on presentation.
  • Fever is intermittent and spiking, usually higher than 38.5° C, and associated with shaking chills.
  • This pattern reflects the transient bacteremia known to occur with the disease.
  • The absence of fever, however, does not exclude the diagnosis of acute cholangitis.
  • In fact, septic patients sometimes present with subnormal temperatures.
  • Likewise, the white blood cell count is usually markedly elevated with this disease, but some patients have normal or low counts, and extremely low white blood cell counts may indicate sepsis.
  • Fever and elevated white blood counts are not specific for acute cholangitis. They are elevated by nearly every acute surgical condition of the abdomen and in systemic infections not arising in the abdomen.

Abdominal pain and jaundice are less common with acute cholangitis and occur in only 50 to 75% of patients. The pattern of presentation changed after 1974.

  • The proportion of patients presenting with fever increased to 92%,
  • whereas the percentage of patients presenting with abdominal pain and jaundice decreased to 67 and 42%.
  • 4 to 5% of patients consistently presented with septic shock, a finding indicating no change in the severity of the illness after 1974.
  • The changing pattern of presentation may reflect a higher proportion of patients with malignant obstruction of the biliary tract in later years.
  • A study of calculous acute cholangitis revealed-
  1. abdominal pain-84%,
  2. fever with chills-90%,
  3. and jaundice in-74% of patients.

Liver function test values are elevated in greater than 90% of patients during an attack of acute cholangitis.

  • These values are not specific for the disease and may have been abnormal before infection developed, as a result of bile duct obstruction.
  • The alkaline phosphatase level is most often elevated, a finding reflecting bile duct obstruction and infection in the biliary system.
  • Hepatocellular enzymes are higher than expected in patients with an isolated biliary problem because of the intense inflammatory reaction and damage to hepatocytes caused by bacteria refluxing in the periductal tissues.
  • Serum bilirubin levels are elevated in most patients, but the degree of elevation is variable.
  • As many as one fifth of patients with cholangitis have a serum bilirubin concentration less than 2 mg/dl, and this finding explains the lack of icterus as a presenting symptom in many patients.
  • Although the degree of hyperbilirubinemia does not correlate with the severity of acute cholangitis, it may be helpful in the differential diagnosis.
  • Low serum bilirubin concentrations (less than 4 to 5 mg/dl and certainly less than 15 mg/dl) are more often associated with benign disease, especially if the patient has a history of biliary colic or pain.
  • Extremely high serum bilirubin values are more likely the result of long-standing bile duct obstruction such as in malignant disease or chronic benign stricture.

Abdominal pain and fever, the most prominent signs of acute cholangitis, also occur in patients with acute cholecystitis, acute pancreatitis, perforated ulcer, ischemic bowel, liver abscess, appendicitis, diverticulitis, acute pyelonephritis, and acute hepatitis.

  • High fever and chills also suggest acute bacterial endocarditis.
  • Septic patients may not exhibit specific signs and symptoms of biliary tract disease, and this situation increases the difficulty in distinguishing among these entities.
  • In most patients, a well-taken history is helpful.
  • Patients with choledocholithiasis often have a history of attacks of biliary colic or intolerances to specific foods that indicate the presence of gallstones.
  • The most common cause of benign biliary stricture is iatrogenic injury, especially after gallbladder surgery.
  • Bile duct stricture should be suspected in any patient who has undergone upper abdominal surgery, especially cholecystectomy or bile duct surgery.
  • Likewise, acute cholangitis is common after manipulation of the biliary tract and should be suspected in a patient with pain or fever after ERCP or percutaneous transhepatic procedures on the bile ducts.
  • Malignant strictures are more indolent.
  1. Patients lose weight and develop painless jaundice before they develop infectious complications.
  2. Eighty per cent of patients with painless jaundice have a malignant bile duct stricture caused by a tumor of the pancreas, bile duct, or duodenum.

Although acute cholangitis causes severe abdominal pain, the pain is usually not associated with significant abdominal tenderness.

  • If well-localized tenderness, rebound tenderness, and other peritoneal signs are present, a cause other than cholangitis should be strongly considered.
  • Pain from cholangitis is usually associated with high fever, a markedly elevated white blood count, and chills.
  • Complicated (perforated or gangrenous) acute cholecystitis may also cause high fever, elevated white blood count, and right upper quadrant pain, but it is more often associated with a palpable mass, peritoneal signs, or localized tenderness directly over the inflamed gallbladder.
  • Likewise, perforated appendicitis, diverticulitis, perforated viscus, and ischemic bowel more often present with an acute surgical abdomen.

No comments: