What is Ascending Cholangitis & How is it Treated?

Ascending cholangitis is a condition where there is infection of the bile duct. Ascending cholangitis can be a fatal condition and should be treated as medical emergency. Ascending cholangitis is also known as acute cholangitis and is commonly caused by bacteria, which ascends or travels from the junction with the duodenum. The risk of ascending cholangitis increases if there is partial obstruction of the bile duct by gallstones. Symptoms of ascending cholangitis include fever, yellow discoloration of the whites of the eyes or skin (jaundice) and pain in the abdomen. Severe symptoms consist of confusion and low blood pressure. Initial treatment consists of antibiotics and intravenous fluids; however, patient commonly also has an underlying problem of narrowing of the bile duct or gallstones which needs further investigations and treatment.

Liver is responsible for producing bile along with helping in eliminating bilirubin and cholesterol from the body. Liver also helps with fats emulsification so that it can be more soluble in water and help with digestion. The liver cells (hepatocytes) form bile and excrete it into the common hepatic duct. There is some amount of bile, which is stored in gall bladder and can be released during digestion. The bile becomes more concentrated by gall bladder as it absorbs dissolved salts and water from it. The rest of the amount of bile reaches the duodenum through the ampulla of Vater and common bile duct . The sphincter of Oddi is present at the junction of the duodenum and ampulla of Vater. This is a circular muscle which controls the release of pancreatic secretions as well as bile into the digestive tract. Due to certain protective mechanisms, bacteria are usually not present in the biliary tree and the sphincter of Oddi functions as a mechanical barrier. There is usually low pressure in the biliary system which allows the bile to freely flow through. Due to this continuous forward flow of the bile, it helps in flushing the bacteria out, if it is present, into the duodenum and prevents infection. The bile composition, which includes immunoglobulin and bile salts, also provide protection from infection.

If the patient has only bacterial contamination without obstruction, then it usually does not result in cholangitis. However, if there is increase in pressure inside the biliary system as a result from bile duct obstruction, then it increases the spaces between the cells which line the duct, which brings the bile contaminated by bacteria in contact with the blood stream. The function of Kupffer cells is also adversely affected. The increase in the biliary pressure also decreases the production of IgA immunoglobulins in the bile resulting in bacteremia and leads to systemic inflammatory response syndrome (SIRS) where the patient has fever, rigors, increased respiratory rate, tachycardia and increased white blood cells. If there is SIRS with suspected or confirmed infection, then it is known as sepsis. The biliary obstruction alone itself damages the immune system and diminishes its capacity for fighting infection. In case of ascending cholangitis, it is thought that the organisms travel backwards into the bile duct due to partial obstruction and hindered function of the sphincter of Oddi.

Obstruction: Obstruction of the bile duct commonly leads to Ascending Cholangitis. This is usually from gallstones.

Cancers: Different tumors, gallbladder cancer, cancer of the bile duct, cancer of the ampulla of Vater, cancer of the duodenum, and pancreatic cancer can cause Ascending Cholangitis.

Parasites: Parasites infecting the liver and bile ducts can also cause ascending cholangitis. These parasites include the roundworm clonorchis sinensis, ascaris lumbricoides and opisthorchis felineus and opisthorchis viverrini .

AIDS: Patients who are suffering from AIDS have a greater tendency for developing ascending cholangitis. However, a huge number of opportunistic organisms which are responsible have substantially decreased since newer and effective treatments of AIDS have been discovered.

Biliary Stent: If the patient has a permanent biliary stent placed, then this also slightly increases the risk of developing ascending cholangitis.

Other Causes: Other causes consist of benign stricturing or bile duct narrowing, which does not have an underlying tumor, postoperative injury or a change in the structure of the bile duct including narrowing where the anastomosis is. Those individuals who have had previous surgery of the biliary system and elderly individuals are at an increased risk for ascending cholangitis.

Ascending cholangitis can also complicate medical procedures which involve the bile duct, particularly ERCP. So, it is recommended that prophylactic antibiotics should be given to patients undergoing ERCP to prevent any complications.

Patient has chills and fever and also complains of pain in the abdomen, specifically in the right upper quadrant. Jaundice and malaise are other symptoms which the patient may experience in Ascending Cholangitis. Upon physical examination, patient usually has tenderness in the right upper quadrant and jaundice. In elderly individuals, there may be atypical presentation of ascending cholangitis where the patient can directly collapse from sepsis without exhibiting the initial typical features of this disease. Patients having an indwelling stent in the bile duct may not develop jaundice.

Charcot’s Triad: A set of three common findings in ascending cholangitis is known as Charcot’s triad and this consists of: jaundice, abdominal pain, and fever. Previously Charcot’s triad was thought to be present in about 50–70% of patients; however, in the recent times, this frequency has reduced.

Reynolds’ Pentad: This consists of the findings of Charcot’s triad along with presence of mental confusion and septic shock. Reynolds’ Pentad which has this combination of symptoms is an indication that the patient’s condition is worsening.

Blood tests reveal features of acute inflammation, such as elevated level of C-reactive protein and increased white blood cell count. Patient also has abnormal liver function tests (LFTs) and in majority of the patients, the LFTs are consistent with obstruction such as increased alkaline phosphatase, bilirubin and gamma-glutamyl transpeptidase. In the initial stages, the tests will be similar that of in hepatitis consisting of increase in aspartate transaminase and alanine transaminase.

Blood cultures are done in patients suffering from fever and with indications of acute infection. Culture of the bile can also be done during ERCP. Gram-negative bacilli are the most common bacteria associated with ascending cholangitis.

As bile duct obstruction is often seen in ascending cholangitis, there are different types of medical imaging tests done to identify the site and nature of this obstruction.

Ultrasound is the first imaging test done, as this is easily available. Ultrasound also helps in differentiating between cholecystitis and cholangitis, as the symptoms of cholecystitis (gallbladder inflammation) resemble the symptoms of cholangitis; however, both the conditions appear differently on ultrasound. Ultrasound scan may show bile duct dilation and helps in identifying about 35% of the bile duct stones. This test, however, is comparatively poor for identifying stones which are present farther into the bile duct.

Magnetic Resonance Cholangiopancreatography (MRCP) is a better test, where magnetic resonance imaging (MRI) is utilized and this test has a comparable sensitivity to ERCP. However, smaller stones can still go undetected on MRCP. It all also depends on the quality of the hospital’s facilities.

Endoscopic Retrograde Cholangiopancreatography (ERCP) is the best investigation for biliary obstruction. In this test, the endoscopy method is used where a tube is passed through the mouth into the esophagus, stomach and from there to the duodenum and a small cannula is passed into the bile duct. In the next step, radiocontrast agent is injected, which helps in opacifying the bile duct. X-rays are then taken so the biliary system can be visualized. On the x-ray images, also known as cholangiograms, gallstones can be visualized on the non-opacified areas in the duct contour.

Endoscopic Ultrasound (EUS) and Computed Tomography (CT) scan are done if causes other than gallstones are thought to cause ascending cholangitis, (such as tumor). Endoscopic ultrasound is helpful in obtaining biopsy of any suspicious masses. CT scan helps in identifying the nature of the obstruction.

Medications & Fluids to Treat Ascending Cholangitis: This condition warrants hospitalization where intravenous fluids are administered to the patient. The patient is also started on broad-spectrum antibiotics. The most widely used combination for treating ascending cholangitis includes penicillin and aminoglycoside. Ciprofloxacin is also effective in many patients and also has fewer side effects. Metronidazole is usually added for treating the anaerobic pathogens, particularly in those patients who are extremely ill or have a risk of developing anaerobic infections. Antibiotics are given for a week to 10 days. If the patient is suffering from low blood pressure, then vasopressors are also given.

Endoscopic Retrograde Cholangiopancreatography (ERCP) For Treating Ascending Cholangitis: The ultimate treatment for ascending cholangitis is relieving the underlying biliary obstruction. This is commonly done after a day or two of hospitalization when the patient has stabilized on antibiotics. However, it can be done as an emergency treatment if the patient continues to deteriorate even with adequate treatment, or in case where the antibiotics are not working and there is no decrease in the signs of infection. ERCP is the commonest method used for unblocking or relieving the bile duct obstruction. In this procedure, the endoscope is passed through the stomach into the duodenum where a small tube is inserted into the bile duct. A sphincterotomy is usually done where a cut is made in the sphincter of Oddi to ease the flow of bile from the duct and to insert the instruments for extracting gallstones, which are blocking the common bile duct. The orifice of the common bile can also be dilated using a balloon. The stones can be removed by using instruments or direct suction. Instruments which are used include baskets and balloons to look at and pull the stones from the bile duct into the duodenum. Mechanical lithotriptor is needed for obstructions caused by larger stones where the stones are crushed by this instrument and then removed. Very large stones, which are causing obstruction and which cannot be removed or broken mechanically because of their size by ERCP, are managed by using extracorporeal shock wave lithotripsy. In this technique, acoustic shock waves are applied outside the body for breaking the stones.

Electrohydraulic Lithotripsy is an alternative technique which is used for removing very large obstructing stones. Electricity is passed through a probe to produce shock waves that break down the obstructing stone.

In rare cases, choledochotomy is done, which is a surgical exploration of the common bile duct and is performed with laparoscopy, for removing the stone.

Stent is used for bridging narrowed areas to keep the bile duct open. Self-expanding metal stents that are permanent are used if the obstruction occurs as a result of pressure from a tumor. Plastic stents that are removable are used if the patient has uncomplicated gallstone disease.

A nasobiliary drain can be left behind so that the bile is drained continuously into a receptible. This is similar to a nasogastric tube; however it passes directly into the common bile duct. Serial x-ray cholangiograms can be easily done to assess the improvement in the obstruction.

The type of treatments for ascending cholangitis depends on the severity of the obstruction, findings on imaging tests, and the degree of improvement in the patient on antibiotic treatment. Some treatments are not safe if the patient has impaired blood clotting, as it increases the risk of bleeding with the use of certain medications, such as clopidogrel or if the PT is prolonged.

If the obstructing stone is present proximal or higher up in the biliary system, then it becomes difficult to access it endoscopically. It is also difficult to access if the obstruction is from a stricture from a previously done anastomosis between the bile duct with the jejunum or duodenum. In such cases, percutaneous transhepatic cholangiography (PTC) is done to alleviate the pressure. In this procedure, ultrasound is used to identify the bile duct and a tube is then passed through the skin. PTC is usually done by radiologists and this procedure carries potential complications. So, it is advisable that additional attempts at ERCP be done by more experienced doctors.

There can be continuous contamination of bile duct from indwelling stents and they require monitoring by regular radiologic testing and changing of the stents.

Cholecystectomy to Treat Ascending Cholangitis: The gallstones which are involved in ascending cholangitis need not originate from the gallbladder, however, cholecystectomy (where the gallbladder is removed surgically) is recommended in patients who have cholangitis from gallstone disease. This procedure is usually not done until there is resolution of all the patient’s symptoms and tests such as ERCP or MRCP have shown that there are no gallstones in the bile duct. Patients who do not undergo cholecystectomy are at an increased risk for recurrent jaundice, biliary pain and further episodes of ascending cholangitis. The risk of mortality is also significantly increased.

There is a considerable risk of death with ascending cholangitis, the primary cause being irreversible shock from multiple organ failure, which can be a complication of severe infections. Recent advancement in the diagnosis and treatment of ascending cholangitis has decreased the mortality rate and improved the prognosis of ascending cholangitis. Patients who are exhibiting signs of multiple organ failure carry a very poor prognosis and eventually die unless treatment with early biliary drainage and systemic antibiotics is started. Some of the other causes of death after ascending cholangitis include pneumonia and heart failure. Some of the factors which worsen the prognosis include female gender, older age, narrowing of bile duct from cancer, history of liver cirrhosis, liver abscesses and acute renal failure. Some of the complications, which occur after ascending cholangitis include respiratory failure, renal failure, cardiac arrhythmia, pneumonia, wound infection, myocardial ischemia and gastrointestinal bleeding.

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