Ascending cholangitis
Encyclopedia
Ascending cholangitis or acute cholangitis (or sometimes cholangitis without a modifier - from Greek chol-, bile + ang-, vessel + itis-, inflammation
) is an infection
of the bile duct
(cholangitis), usually caused by bacteria
ascending from its junction with the duodenum
(first part of the small intestine
). It tends to occur if the bile duct is already partially obstructed by gallstone
s.
Cholangitis can be life-threatening, and is regarded as a medical emergency
. Characteristic symptoms include jaundice
, fever
, abdominal pain
, and in severe cases, low blood pressure
and confusion
. Initial treatment is with intravenous fluids and antibiotic
s, but there is often an underlying problem (such as gallstone
s or narrowing
in the bile duct) for which further tests and treatments may be necessary, usually in the form of endoscopy
to relieve obstruction of the bile duct.
(particularly in the right upper quadrant of the abdomen), fever
, rigors
(uncontrollable shaking) and a feeling of uneasiness (malaise
). Some may report jaundice
(yellow discoloration of the skin and the whites of the eyes).
Physical examination
findings typically include jaundice
and right upper quadrant tenderness. Charcot's triad is a set of three common findings in cholangitis: abdominal pain, jaundice, and fever. This was assumed in the past to be present in 50–70% of cases, although more recently the frequency has been reported as 15–20%. Reynolds' pentad
includes the findings of Charcot's triad with the presence of septic shock
and mental confusion
. This combination of symptoms indicates worsening of the condition and the development of sepsis
, and is seen less commonly still.
In the elderly, the presentation may be atypical; they may directly collapse due to septicemia without first showing typical features. Those with an indwelling stent in the bile duct (see below) may not develop jaundice.
s. 10–30% of cases, however, are due to other causes such as benign
stricturing (narrowing of the bile duct without an underlying tumor), postoperative damage or an altered structure of the bile ducts such as narrowing at the site of an anastomosis
(surgical connection) and various tumors (cancer of the bile duct
, gallbladder cancer
, cancer of the ampulla of Vater, pancreatic cancer
or cancer of the duodenum
). Cholangitis may also complicate medical procedures involving the bile duct, especially ERCP. To prevent this, it is recommended that those undergoing ERCP for any indication receive prophylactic (preventative) antibiotics.
The presence of a permanent biliary stent (e.g. in pancreatic cancer) slightly increases the risk of cholangitis, but stents of this type are often needed to keep the bile duct patent under outside pressure.
s show features of acute inflammation (raised white blood cell
count and elevated C-reactive protein
level), and usually abnormal liver function tests
(LFTs). In most cases the LFTs will be consistent with obstruction: raised bilirubin
, alkaline phosphatase
and γ-glutamyl transpeptidase. In the early stages, however, pressure on the liver cells may be the main feature and the tests will resemble those in hepatitis
, with elevations in alanine transaminase
and aspartate transaminase
.
Blood culture
s are often performed in people with fever and evidence of acute infection. These yield the bacteria causing the infection in 36% of cases, usually after 24–48 hours of incubation. Bile, too, may be sent for culture during ERCP (see below). The most common bacteria linked to ascending cholangitis are gram-negative bacilli
: Escherichia coli
(25–50%), Klebsiella
(15–20%) and Enterobacter
(5–10%). Of the gram-positive cocci
, Enterococcus
causes 10–20%. A small proportion of cases, especially in the elderly and those who have undergone previous surgery of the biliary system, is due to anaerobic organism
s such as Clostridium
and Bacteroides
. In the developing world, cholangitis may also be caused by parasites such as Ascaris lumbricoides
and Clonorchis sinensis
. In people with AIDS
, a large number of opportunistic organisms has been known to cause AIDS cholangiopathy, but the risk has rapidly diminished since the introduction of effective AIDS treatment
.
Given that ascending cholangitis usually occurs in the setting of bile duct obstruction, various forms of medical imaging
may be employed to identify the site and nature of this obstruction. The first investigation is usually ultrasound
, as this is the most easily available. Ultrasound may show dilation of the bile duct and identifies 38% of bile duct stones; it is relatively poor at identifying stones further down the bile duct. Ultrasound can help distinguish between cholangitis and cholecystitis
(inflammation of the gallbladder), which has similar symptoms to cholangitis but appears differently on ultrasound. A better test is magnetic resonance cholangiopancreatography
(MRCP), which uses magnetic resonance imaging
(MRI); this has a comparable sensitivity to ERCP. Smaller stones, however, can still be missed on MRCP depending on the quality of the hospital's facilities.
The gold standard
(best possible) test for biliary obstruction is still endoscopic retrograde cholangiopancreatography
(ERCP). This involves the use of endoscopy
(passing a tube through the mouth into the esophagus
, stomach
and thence to the duodenum
) to pass a small cannula into the bile duct. At that point, radiocontrast
is injected to opacify the duct, and X-ray
s are taken to get a visual impression of the biliary system. On the endoscopic image of the ampulla, one can sometimes see a protuberant ampulla from an impacted gallstone in the common bile duct, or the frank extrusion of pus from the common bile duct orifice. On the X-ray images (known as cholangiograms
), gallstones are visible as nonopacified areas in the contour of the duct. For diagnostic purposes, ERCP has now generally been replaced by MRCP. ERCP is only used first-line in critically ill patients in whom delay for diagnostic tests is not acceptable; however, if the index of suspicion for cholangitis is high, an ERCP is typically done to achieve drainage of the obstructed common bile duct.
If other causes rather than gallstones are suspected (such as a tumor
), computed tomography
and endoscopic ultrasound
(EUS) may be performed to identify the nature of the obstruction. EUS may be used to obtain biopsy
(tissue sample) of suspicious masses. EUS may also replace diagnostic ERCP for stone disease, although this depends on local availability.
and bilirubin
from the body, as well as emulsifying
of fats to make them more soluble in water and aid in their digestion. Bile is formed in the liver by hepatocyte
s (liver cells) and excreted into the common hepatic duct
. Part of the bile is stored in the gall bladder because of back pressure (exerted by the sphincter of Oddi
), and may be released at time of digestion. The gall bladder also concentrates the bile by absorbing water and dissolved salts from it. All bile reaches the duodenum
(first part of the small intestine) through the common bile duct
and the ampulla of Vater. The sphincter of Oddi, located at the junction of the ampulla of Vater and the duodenum, is a circular muscle that controls the release of both bile and pancreatic
secretions
into the digestive tract.
The biliary tree is normally relatively free of bacteria because of certain protective mechanisms. The sphincter of Oddi acts as a mechanical barrier. The biliary system normally has low pressure (8 to 12 cmH2O
) and allows bile to flow freely through. The continuous forward flow of the bile in the duct flushes bacteria, if present, into the duodenum, and does not allow establishment of an infection. The constitution of bile—bile salts and immunoglobulin secreted by the epithelium
of the bile duct also has a protective role.
Bacterial contamination alone in absence of obstruction does not usually result in cholangitis. However increased pressure within the biliary system (above 20 cmH2O) resulting from obstruction in the bile duct widens spaces between the cells lining the duct, bringing bacterially contaminated bile in contact with the blood stream. It also adversely affects the function of Kupffer cells, which are specialized macrophage
cells that assist in preventing bacteria from entering the biliary system. Finally, increased biliary pressure decreases production of IgA
immunoglobulins in the bile. This results in bacteremia
(bacteria in the blood stream) and gives rise to the systemic inflammatory response syndrome
(SIRS) comprising fever (often with rigors
), tachycardia
, increased respiratory rate
and increased white blood cell count; SIRS in the presence of suspected or confirmed infection is called sepsis
. Biliary obstruction itself disadvantages the immune system
and impairs its capability to fight infection, by impairing the function of certain immune system cells (neutrophil granulocyte
s) and modifying the levels of immune hormones (cytokine
s).
In ascending cholangitis, it is assumed that organisms migrate backwards up the bile duct as a result of partial obstruction and decreased function of the sphincter of Oddi. Other theories about the origin of the bacteria, such as through the portal vein or transmigration from the colon
, are considered less likely.
s are commenced. Empirical treatment
with broad-spectrum antibiotic
s is usually necessary until it is known for certain which pathogen is causing the infection, and to which antibiotics it is sensitive. Combinations of penicillin
s and aminoglycoside
s are widely used, although ciprofloxacin
has been shown to be effective in most cases, and may be preferred to aminoglycosides because of fewer side effects. Metronidazole
is often added to specifically treat the anaerobic pathogens, especially in those who are very ill or at risk of anaerobic infections. Antibiotics are continued for 7–10 days. Drugs that increase the blood pressure (vasopressors
) may also be required to counter the low blood pressure.
Endoscopic retrograde cholangiopancreatography
(ERCP) is the most common approach in unblocking the bile duct. This involves endoscopy (passing a fiberoptic tube through the stomach into the duodenum), identification of the ampulla of Vater and insertion of a small tube into the bile duct. A sphincterotomy (making a cut in the sphincter of Oddi) is typically done to ease the flow of bile from the duct and to allow insertion of instruments to extract gallstones that are obstructing the common bile duct
; alternatively or additionally, the common bile duct orifice can be dilated with a balloon. Stones may be removed either by direct suction or by using various instruments, including balloons and baskets to trawl the bile duct in order to pull stones into the duodenum. Obstructions that are caused by larger stones may require the use of an instrument known as a mechanical lithotriptor
in order to crush the stone prior to removal. Obstructing stones that are too large to be removed or broken mechanically by ERCP may be managed by extracorporeal shock wave lithotripsy. This technique uses acoustic shock waves administered outside the body to break down the stones. An alternative technique to remove very large obstructing stones is electrohydraulic lithotripsy, where a small endoscope known as a cholangioscope is inserted by ERCP to directly visualize the stone. A probe uses electricity to generate shock waves that break down the obstructing stone. Rarely, surgical exploration of the common bile duct (termed choledochotomy), which can be performed with laparoscopy
, is required to remove the stone.
Narrowed areas may be bridged by a stent
, a hollow tube that keeps the duct open. Removable plastic stents are used in uncomplicated gallstone disease, while permanent self-expanding metal stents
with a longer lifespan are used if the obstruction is due to pressure from a tumor such as pancreatic cancer
. A nasobiliary drain may be left behind; this is a plastic tube that passes from the bile duct through the stomach and the nose and allows continuous drainage of bile into a receptible. It is similar to a nasogastric tube, but passes into the common bile duct directly, and allows for serial x-ray cholangiograms to be done to identify the improvement of the obstruction. The decision on which of the aforementioned treatments to apply is generally based on the severity of the obstruction, findings on other imaging studies, and whether the patient has improved with antibiotic treatment. Certain treatments may be unsafe if blood clotting
is impaired, as the risk of bleeding (especially from sphincterotomy) is increased in the use of medication such as clopidogrel
(which inhibits platelet
aggregation) or if the prothrombin time
is significantly prolonged. For a prolonged prothrombin time, vitamin K
or fresh frozen plasma
may be administered to reduce bleeding risk.
It may be difficult to obtain endoscopic access to the obstruction located higher (proximal) up in the biliary system, or when it is due to a stricture in the priorly performed anastomosis between the bile duct (surgically joining) with the duodenum or jejunum
. When this happens, percutaneous transhepatic cholangiography
(PTC) may be needed to relieve pressure. This involves identifying the bile duct by ultrasound and then passing a tube through the skin (percutaneous). PTC is generally performed by radiologists
. PTC has potential complications, so occasionally further attempts at ERCP by more experienced doctors are preferred.
Continual contamination of bile duct by indwelling stents (as may occur in chronic conditions like tumor of the head of pancreas
) requires monitoring by repeated radiologic tests and changing of the stents.
(surgical removal of the gallbladder) is generally recommended in people who have been treated for cholangitis due to gallstone disease. This is typically delayed until all symptoms have resolved and ERCP or MRCP have confirmed that the bile duct is clear of gallstones. Those who do not undergo cholecystectomy have an increased risk of recurrent biliary pain, jaundice, further episodes of cholangitis, and need for further ERCP or related procedures; the risk of death is also significantly increased.
.
Risk factors indicating an increased risk of death include older age, female gender, a history of liver cirrhosis
, biliary narrowing due to cancer
, acute renal failure
and the presence of liver abscess
es. Complications following severe cholangitis include renal failure, respiratory failure
(inability of the respiratory system to oxygenate blood and/or eliminate carbon dioxide), cardiac arrythmia, wound infection, pneumonia
, gastrointestinal bleeding
and myocardial ischemia
(lack of blood flow to the heart, leading to heart attacks
).
(abdominal pain due to the passage of gallstones through the bile duct into the digestive tract), and 2–3% will develop complications of obstruction: acute pancreatitis
, cholecystitis
or acute cholangitis. Prevalence of gallstone disease increases with age and body mass index
(a marker of obesity
). However, risk is also increased in those who lose weight rapidly (e.g. after weight loss surgery
) due to alterations in the composition of the bile that makes it prone to form stones. Gallstones are slightly more common in women than in men, and pregnancy increases the risk further.
, working at the Salpêtrière Hospital
in Paris, France, is credited with early reports of cholangitis, as well as his eponymous triad, in 1877. He referred to the condition as "hepatic fever" (fièvre hépatique). Dr Benedict M. Reynolds, an American surgeon, reignited interest in the condition in his 1959 report with colleague Dr Everett L. Dargan, and formulated the pentad that carries his name. It remained a condition generally treated by surgeons, with exploration of the bile duct and excision of gallstones, until the ascendancy of ERCP in 1968. ERCP is generally performed by internal medicine or gastroenterology specialists. In 1992 it was shown that ERCP was generally safer than surgical intervention in ascending cholangitis.
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
) is an infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
of the bile duct
Bile duct
A bile duct is any of a number of long tube-like structures that carry bile.Bile, required for the digestion of food, is excreted by the liver into passages that carry bile toward the hepatic duct, which joins with the cystic duct to form the common bile duct, which opens into the intestine.The...
(cholangitis), usually caused by bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
ascending from its junction with the duodenum
Duodenum
The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum...
(first part of the small intestine
Small intestine
The small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...
). It tends to occur if the bile duct is already partially obstructed by gallstone
Gallstone
A gallstone is a crystalline concretion formed within the gallbladder by accretion of bile components. These calculi are formed in the gallbladder, but may pass distally into other parts of the biliary tract such as the cystic duct, common bile duct, pancreatic duct, or the ampulla of...
s.
Cholangitis can be life-threatening, and is regarded as a medical emergency
Medical emergency
A medical emergency is an injury or illness that is acute and poses an immediate risk to a person's life or long term health. These emergencies may require assistance from another person, who should ideally be suitably qualified to do so, although some of these emergencies can be dealt with by the...
. Characteristic symptoms include jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
, fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, abdominal pain
Abdominal pain
Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
, and in severe cases, low blood pressure
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
and confusion
Mental confusion
Confusion of a pathological degree usually refers to loss of orientation sometimes accompanied by disordered consciousness and often memory Confusion (from Latin confusĭo, -ōnis, noun of action from confundere "to pour together", also "to confuse") of a pathological degree usually refers to loss...
. Initial treatment is with intravenous fluids and antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s, but there is often an underlying problem (such as gallstone
Gallstone
A gallstone is a crystalline concretion formed within the gallbladder by accretion of bile components. These calculi are formed in the gallbladder, but may pass distally into other parts of the biliary tract such as the cystic duct, common bile duct, pancreatic duct, or the ampulla of...
s or narrowing
Stenosis
A stenosis is an abnormal narrowing in a blood vessel or other tubular organ or structure.It is also sometimes called a stricture ....
in the bile duct) for which further tests and treatments may be necessary, usually in the form of endoscopy
Endoscopy
Endoscopy means looking inside and typically refers to looking inside the body for medical reasons using an endoscope , an instrument used to examine the interior of a hollow organ or cavity of the body. Unlike most other medical imaging devices, endoscopes are inserted directly into the organ...
to relieve obstruction of the bile duct.
Signs and symptoms
A person with cholangitis may complain of abdominal painAbdominal pain
Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...
(particularly in the right upper quadrant of the abdomen), fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, rigors
Rigor (medicine)
Rigor is a shaking occurring during a high fever. It occurs because cytokines and prostaglandins are released as part of an immune response and increase the set point for body temperature in the hypothalamus....
(uncontrollable shaking) and a feeling of uneasiness (malaise
Malaise
Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...
). Some may report jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
(yellow discoloration of the skin and the whites of the eyes).
Physical examination
Physical examination
Physical examination or clinical examination is the process by which a doctor investigates the body of a patient for signs of disease. It generally follows the taking of the medical history — an account of the symptoms as experienced by the patient...
findings typically include jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
and right upper quadrant tenderness. Charcot's triad is a set of three common findings in cholangitis: abdominal pain, jaundice, and fever. This was assumed in the past to be present in 50–70% of cases, although more recently the frequency has been reported as 15–20%. Reynolds' pentad
Reynolds' pentad
Reynolds' pentad is a collection of signs and symptoms suggesting the diagnosis of septic or ascending cholangitis, a serious infection of the biliary system. It is a combination of Charcot's triad with hypotension and an altered mental state.-Eponym:It was named after the surgeon, B.M...
includes the findings of Charcot's triad with the presence of septic shock
Septic shock
Septic shock is a medical emergency caused by decreased tissue perfusion and oxygen delivery as a result of severe infection and sepsis, though the microbe may be systemic or localized to a particular site. It can cause multiple organ dysfunction syndrome and death...
and mental confusion
Mental confusion
Confusion of a pathological degree usually refers to loss of orientation sometimes accompanied by disordered consciousness and often memory Confusion (from Latin confusĭo, -ōnis, noun of action from confundere "to pour together", also "to confuse") of a pathological degree usually refers to loss...
. This combination of symptoms indicates worsening of the condition and the development of sepsis
Sepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...
, and is seen less commonly still.
In the elderly, the presentation may be atypical; they may directly collapse due to septicemia without first showing typical features. Those with an indwelling stent in the bile duct (see below) may not develop jaundice.
Causes
Bile duct obstruction, which is usually present in acute cholangitis, is generally due to gallstoneGallstone
A gallstone is a crystalline concretion formed within the gallbladder by accretion of bile components. These calculi are formed in the gallbladder, but may pass distally into other parts of the biliary tract such as the cystic duct, common bile duct, pancreatic duct, or the ampulla of...
s. 10–30% of cases, however, are due to other causes such as benign
Benign
A benign tumor is a tumor that lacks the ability to metastasize. Common examples of benign tumors include moles and uterine fibroids.The term "benign" implies a mild and nonprogressive disease. Indeed, many kinds of benign tumors are harmless to human health...
stricturing (narrowing of the bile duct without an underlying tumor), postoperative damage or an altered structure of the bile ducts such as narrowing at the site of an anastomosis
Anastomosis
An anastomosis is the reconnection of two streams that previously branched out, such as blood vessels or leaf veins. The term is used in medicine, biology, mycology and geology....
(surgical connection) and various tumors (cancer of the bile duct
Cholangiocarcinoma
Cholangiocarcinoma is a cancer of the bile ducts which drain bile from the liver into the small intestine. Other biliary tract cancers include pancreatic cancer, gallbladder cancer, and cancer of the ampulla of Vater...
, gallbladder cancer
Gallbladder cancer
Gallbladder cancer is a relatively uncommon cancer. It has peculiar geographical distribution being common in central and South America, central and eastern Europe, Japan and northern India; it is also common in certain ethnic groups e.g. Native American Indians and Hispanics. If it is diagnosed...
, cancer of the ampulla of Vater, pancreatic cancer
Pancreatic cancer
Pancreatic cancer refers to a malignant neoplasm of the pancreas. The most common type of pancreatic cancer, accounting for 95% of these tumors is adenocarcinoma, which arises within the exocrine component of the pancreas. A minority arises from the islet cells and is classified as a...
or cancer of the duodenum
Small intestine cancer
In oncology, small intestine cancer, also small bowel cancer and cancer of the small bowel, is a cancer of the small intestine. It is relatively rare compared to other gastrointestinal malignancies such as gastric cancer and colorectal cancer.Small intestine cancer can be subdivided into duodenal...
). Cholangitis may also complicate medical procedures involving the bile duct, especially ERCP. To prevent this, it is recommended that those undergoing ERCP for any indication receive prophylactic (preventative) antibiotics.
The presence of a permanent biliary stent (e.g. in pancreatic cancer) slightly increases the risk of cholangitis, but stents of this type are often needed to keep the bile duct patent under outside pressure.
Blood tests
Routine blood testBlood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
s show features of acute inflammation (raised white blood cell
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
count and elevated C-reactive protein
C-reactive protein
C-reactive protein is a protein found in the blood, the levels of which rise in response to inflammation...
level), and usually abnormal liver function tests
Liver function tests
Liver function tests , are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver. The parameters measured include PT/INR, aPTT, albumin, billirubin and others...
(LFTs). In most cases the LFTs will be consistent with obstruction: raised bilirubin
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
, alkaline phosphatase
Alkaline phosphatase
Alkaline phosphatase is a hydrolase enzyme responsible for removing phosphate groups from many types of molecules, including nucleotides, proteins, and alkaloids. The process of removing the phosphate group is called dephosphorylation...
and γ-glutamyl transpeptidase. In the early stages, however, pressure on the liver cells may be the main feature and the tests will resemble those in hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
, with elevations in alanine transaminase
Alanine transaminase
Alanine transaminase or ALT is a transaminase enzyme . It is also called serum glutamic pyruvic transaminase or alanine aminotransferase ....
and aspartate transaminase
Aspartate transaminase
Aspartate transaminase , also called aspartate aminotransferase or serum glutamic oxaloacetic transaminase , is a pyridoxal phosphate -dependent transaminase enzyme . AST catalyzes the reversible transfer of an α-amino group between aspartate and glutamate and, as such, is an important enzyme in...
.
Blood culture
Blood culture
Blood culture is a microbiological culture of blood. It is employed to detect infections that are spreading through the bloodstream...
s are often performed in people with fever and evidence of acute infection. These yield the bacteria causing the infection in 36% of cases, usually after 24–48 hours of incubation. Bile, too, may be sent for culture during ERCP (see below). The most common bacteria linked to ascending cholangitis are gram-negative bacilli
Bacilli
Bacilli refers to a taxonomic class of bacteria. It includes two orders, Bacillales and Lactobacillales, which contain several well-known pathogens like Bacillus anthracis .-Ambiguity:...
: Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
(25–50%), Klebsiella
Klebsiella
Klebsiella is a genus of non-motile, Gram-negative, oxidase-negative, rod-shaped bacteria with a prominent polysaccharide-based capsule. It is named after the German microbiologist Edwin Klebs...
(15–20%) and Enterobacter
Enterobacter
Enterobacter is a genus of common Gram-negative, facultatively-anaerobic, rod-shaped bacteria of the family Enterobacteriaceae. Several strains of the these bacteria are pathogenic and cause opportunistic infections in immunocompromised hosts and in those who are on mechanical ventilation...
(5–10%). Of the gram-positive cocci
Coccus
Coccus can be used to describe any bacterium that has a spherical shape. It is one of the three distinct types of bacteria shapes, the other two being bacillus and spirillum cells...
, Enterococcus
Enterococcus
Enterococcus is a genus of lactic acid bacteria of the phylum Firmicutes. Enterococci are Gram-positive cocci that often occur in pairs or short chains, and are difficult to distinguish from streptococci on physical characteristics alone. Two species are common commensal organisms in the...
causes 10–20%. A small proportion of cases, especially in the elderly and those who have undergone previous surgery of the biliary system, is due to anaerobic organism
Anaerobic organism
An anaerobic organism or anaerobe is any organism that does not require oxygen for growth. It could possibly react negatively and may even die if oxygen is present...
s such as Clostridium
Clostridium
Clostridium is a genus of Gram-positive bacteria, belonging to the Firmicutes. They are obligate anaerobes capable of producing endospores. Individual cells are rod-shaped, which gives them their name, from the Greek kloster or spindle...
and Bacteroides
Bacteroides
Bacteroides is a genus of Gram-negative, bacillus bacteria. Bacteroides species are non-endospore-forming, anaerobes, and may be either motile or non-motile, depending on the species. The DNA base composition is 40-48% GC. Unusual in bacterial organisms, Bacteroides membranes contain sphingolipids...
. In the developing world, cholangitis may also be caused by parasites such as Ascaris lumbricoides
Ascaris lumbricoides
Ascaris lumbricoides is the giant roundworm of humans, belonging to the phylum Nematoda. An ascarid nematode, it is responsible for the disease ascariasis in humans, and it is the largest and most common parasitic worm in humans. One-sixth of the human population is estimated to be infected by this...
and Clonorchis sinensis
Clonorchis sinensis
Clonorchis sinensis, the Chinese liver fluke, is a human liver fluke in the class Trematoda, Phylum Platyhelminthes. This parasite lives in the liver of humans, and is found mainly in the common bile duct and gall bladder, feeding on bile...
. In people with AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
, a large number of opportunistic organisms has been known to cause AIDS cholangiopathy, but the risk has rapidly diminished since the introduction of effective AIDS treatment
Antiretroviral drug
Antiretroviral drugs are medications for the treatment of infection by retroviruses, primarily HIV. When several such drugs, typically three or four, are taken in combination, the approach is known as Highly Active Antiretroviral Therapy, or HAART...
.
Medical imaging
Medical imaging
Medical imaging is the technique and process used to create images of the human body for clinical purposes or medical science...
may be employed to identify the site and nature of this obstruction. The first investigation is usually ultrasound
Medical ultrasonography
Diagnostic sonography is an ultrasound-based diagnostic imaging technique used for visualizing subcutaneous body structures including tendons, muscles, joints, vessels and internal organs for possible pathology or lesions...
, as this is the most easily available. Ultrasound may show dilation of the bile duct and identifies 38% of bile duct stones; it is relatively poor at identifying stones further down the bile duct. Ultrasound can help distinguish between cholangitis and cholecystitis
Cholecystitis
-Signs and symptoms:Cholecystitis usually presents as a pain in the right upper quadrant. This is known as biliary colic. This is initially intermittent, but later usually presents as a constant, severe pain. During the initial stages, the pain may be felt in an area totally separate from the site...
(inflammation of the gallbladder), which has similar symptoms to cholangitis but appears differently on ultrasound. A better test is magnetic resonance cholangiopancreatography
Magnetic resonance cholangiopancreatography
Magnetic resonance cholangiopancreatography is a medical imaging technique that uses magnetic resonance imaging to visualise the biliary and pancreatic ducts in a non-invasive manner...
(MRCP), which uses magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
(MRI); this has a comparable sensitivity to ERCP. Smaller stones, however, can still be missed on MRCP depending on the quality of the hospital's facilities.
The gold standard
Gold standard (test)
In medicine and statistics, gold standard test refers to a diagnostic test or benchmark that is the best available under reasonable conditions. It does not have to be necessarily the best possible test for the condition in absolute terms...
(best possible) test for biliary obstruction is still endoscopic retrograde cholangiopancreatography
Endoscopic retrograde cholangiopancreatography
Endoscopic retrograde cholangiopancreatography is a technique that combines the use of endoscopy and fluoroscopy to diagnose and treat certain problems of the biliary or pancreatic ductal systems...
(ERCP). This involves the use of endoscopy
Endoscopy
Endoscopy means looking inside and typically refers to looking inside the body for medical reasons using an endoscope , an instrument used to examine the interior of a hollow organ or cavity of the body. Unlike most other medical imaging devices, endoscopes are inserted directly into the organ...
(passing a tube through the mouth into the esophagus
Esophagus
The esophagus is an organ in vertebrates which consists of a muscular tube through which food passes from the pharynx to the stomach. During swallowing, food passes from the mouth through the pharynx into the esophagus and travels via peristalsis to the stomach...
, stomach
Stomach
The stomach is a muscular, hollow, dilated part of the alimentary canal which functions as an important organ of the digestive tract in some animals, including vertebrates, echinoderms, insects , and molluscs. It is involved in the second phase of digestion, following mastication .The stomach is...
and thence to the duodenum
Duodenum
The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum...
) to pass a small cannula into the bile duct. At that point, radiocontrast
Radiocontrast
Radiocontrast agents are a type of medical contrast medium used to improve the visibility of internal bodily structures in an X-ray based imaging techniques such as computed tomography or radiography...
is injected to opacify the duct, and X-ray
X-ray
X-radiation is a form of electromagnetic radiation. X-rays have a wavelength in the range of 0.01 to 10 nanometers, corresponding to frequencies in the range 30 petahertz to 30 exahertz and energies in the range 120 eV to 120 keV. They are shorter in wavelength than UV rays and longer than gamma...
s are taken to get a visual impression of the biliary system. On the endoscopic image of the ampulla, one can sometimes see a protuberant ampulla from an impacted gallstone in the common bile duct, or the frank extrusion of pus from the common bile duct orifice. On the X-ray images (known as cholangiograms
Cholangiography
Cholangiography is the imaging of the bile duct by x-rays. There are at least two kinds of cholangiography:* percutaneous transhepatic cholangiography : Examination of liver and bile ducts by x-rays...
), gallstones are visible as nonopacified areas in the contour of the duct. For diagnostic purposes, ERCP has now generally been replaced by MRCP. ERCP is only used first-line in critically ill patients in whom delay for diagnostic tests is not acceptable; however, if the index of suspicion for cholangitis is high, an ERCP is typically done to achieve drainage of the obstructed common bile duct.
If other causes rather than gallstones are suspected (such as a tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
), computed tomography
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
and endoscopic ultrasound
Endoscopic ultrasound
Endoscopic ultrasound or echo-endoscopy is a medical procedure in endoscopy is combined with ultrasound to obtain images of the internal organs in the chest and abdomen. It can be used to visualize the wall of these organs, or to look at adjacent structures...
(EUS) may be performed to identify the nature of the obstruction. EUS may be used to obtain biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
(tissue sample) of suspicious masses. EUS may also replace diagnostic ERCP for stone disease, although this depends on local availability.
Pathogenesis
Bile is produced by the liver, and serves to eliminate cholesterolCholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
and bilirubin
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
from the body, as well as emulsifying
Emulsion
An emulsion is a mixture of two or more liquids that are normally immiscible . Emulsions are part of a more general class of two-phase systems of matter called colloids. Although the terms colloid and emulsion are sometimes used interchangeably, emulsion is used when both the dispersed and the...
of fats to make them more soluble in water and aid in their digestion. Bile is formed in the liver by hepatocyte
Hepatocyte
A hepatocyte is a cell of the main tissue of the liver. Hepatocytes make up 70-80% of the liver's cytoplasmic mass.These cells are involved in:* Protein synthesis* Protein storage* Transformation of carbohydrates...
s (liver cells) and excreted into the common hepatic duct
Common hepatic duct
The common hepatic duct is the duct formed by the convergence of the right hepatic duct and the left hepatic duct . The common hepatic duct then joins the cystic duct coming from the gallbladder to form the common bile duct...
. Part of the bile is stored in the gall bladder because of back pressure (exerted by the sphincter of Oddi
Sphincter of Oddi
The sphincter of ampulla or sphincter of Oddi is a muscular valve that controls the flow of digestive juices through the ampulla of Vater into the second part of the duodenum. It is named after Ruggero Oddi...
), and may be released at time of digestion. The gall bladder also concentrates the bile by absorbing water and dissolved salts from it. All bile reaches the duodenum
Duodenum
The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum...
(first part of the small intestine) through the common bile duct
Common bile duct
The common bile duct is a tube-like anatomic structure in the human gastrointestinal tract. It is formed by the union of the common hepatic duct and the cystic duct . It is later joined by the pancreatic duct to form the ampulla of Vater...
and the ampulla of Vater. The sphincter of Oddi, located at the junction of the ampulla of Vater and the duodenum, is a circular muscle that controls the release of both bile and pancreatic
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
secretions
Pancreatic juice
Pancreatic juice is a liquid secreted by the pancreas, which contains a variety of enzymes, including trypsinogen, chymotrypsinogen, elastase, carboxypeptidase, pancreatic lipase, and amylase....
into the digestive tract.
The biliary tree is normally relatively free of bacteria because of certain protective mechanisms. The sphincter of Oddi acts as a mechanical barrier. The biliary system normally has low pressure (8 to 12 cmH2O
Centimetre of water
A centimetre of water is a less commonly used unit of pressure derived from pressure head calculations using metrology...
) and allows bile to flow freely through. The continuous forward flow of the bile in the duct flushes bacteria, if present, into the duodenum, and does not allow establishment of an infection. The constitution of bile—bile salts and immunoglobulin secreted by the epithelium
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
of the bile duct also has a protective role.
Bacterial contamination alone in absence of obstruction does not usually result in cholangitis. However increased pressure within the biliary system (above 20 cmH2O) resulting from obstruction in the bile duct widens spaces between the cells lining the duct, bringing bacterially contaminated bile in contact with the blood stream. It also adversely affects the function of Kupffer cells, which are specialized macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...
cells that assist in preventing bacteria from entering the biliary system. Finally, increased biliary pressure decreases production of IgA
IGA
Iga or IGA may stand for:-Given name:* a female given name of Polish origin. The name originates from the female given name Jadwiga and stands for gia,or gina in the USA....
immunoglobulins in the bile. This results in bacteremia
Bacteremia
Bacteremia is the presence of bacteria in the blood. The blood is normally a sterile environment, so the detection of bacteria in the blood is always abnormal....
(bacteria in the blood stream) and gives rise to the systemic inflammatory response syndrome
Systemic inflammatory response syndrome
Systemic inflammatory response syndrome is an inflammatory state affecting the whole body, frequently a response of the immune system to infection, but not necessarily so...
(SIRS) comprising fever (often with rigors
Rigor (medicine)
Rigor is a shaking occurring during a high fever. It occurs because cytokines and prostaglandins are released as part of an immune response and increase the set point for body temperature in the hypothalamus....
), tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
, increased respiratory rate
Respiratory rate
Respiratory rate is also known by respiration rate, pulmonary ventilation rate, ventilation rate, or breathing frequency is the number of breaths taken within a set amount of time, typically 60 seconds....
and increased white blood cell count; SIRS in the presence of suspected or confirmed infection is called sepsis
Sepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...
. Biliary obstruction itself disadvantages the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
and impairs its capability to fight infection, by impairing the function of certain immune system cells (neutrophil granulocyte
Neutrophil granulocyte
Neutrophil granulocytes are the most abundant type of white blood cells in mammals and form an essential part of the innate immune system. They are generally referred to as either neutrophils or polymorphonuclear neutrophils , and are subdivided into segmented neutrophils and banded neutrophils...
s) and modifying the levels of immune hormones (cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s).
In ascending cholangitis, it is assumed that organisms migrate backwards up the bile duct as a result of partial obstruction and decreased function of the sphincter of Oddi. Other theories about the origin of the bacteria, such as through the portal vein or transmigration from the colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
, are considered less likely.
Fluids and antibiotics
Cholangitis requires admission to hospital. Intravenous fluids are administered, especially if the blood pressure is low, and antibioticAntibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
s are commenced. Empirical treatment
Empirical treatment
Empirical treatment is a medical treatment not derived from the scientific method, but derived from observation, survey or common use.In the medical profession, the term is also used when treatment is started before a diagnosis is confirmed The most common reason is that investigations are...
with broad-spectrum antibiotic
Broad-spectrum antibiotic
The term broad-spectrum antibiotic refers to an antibiotic that acts against a wide range of disease-causing bacteria. A broad-spectrum antibiotic acts against both Gram-positive and Gram-negative bacteria, in contrast to a narrow-spectrum antibiotic, which is effective against specific families of...
s is usually necessary until it is known for certain which pathogen is causing the infection, and to which antibiotics it is sensitive. Combinations of penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
s and aminoglycoside
Aminoglycoside
An aminoglycoside is a molecule or a portion of a molecule composed of amino-modifiedsugars.Several aminoglycosides function as antibiotics that are effective against certain types of bacteria...
s are widely used, although ciprofloxacin
Ciprofloxacin
Ciprofloxacin is a synthetic chemotherapeutic antibiotic of the fluoroquinolone drug class.It is a second-generation fluoroquinolone antibacterial. It kills bacteria by interfering with the enzymes that cause DNA to rewind after being copied, which stops synthesis of DNA and of...
has been shown to be effective in most cases, and may be preferred to aminoglycosides because of fewer side effects. Metronidazole
Metronidazole
Metronidazole is a nitroimidazole antibiotic medication used particularly for anaerobic bacteria and protozoa. Metronidazole is an antibiotic, amebicide, and antiprotozoal....
is often added to specifically treat the anaerobic pathogens, especially in those who are very ill or at risk of anaerobic infections. Antibiotics are continued for 7–10 days. Drugs that increase the blood pressure (vasopressors
Vasoconstriction
Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, particularly the large arteries, small arterioles and veins. The process is the opposite of vasodilation, the widening of blood vessels. The process is particularly important in...
) may also be required to counter the low blood pressure.
Endoscopy
The definitive treatment for cholangitis is relief of the underlying biliary obstruction. This is usually deferred until 24–48 hours after admission, when the patient is stable and has shown some improvement with antibiotics, but may need to happen as an emergency in case of ongoing deterioration despite adequate treatment, or if antibiotics are not effective in reducing the signs of infection (which happens in 15% of cases).Endoscopic retrograde cholangiopancreatography
Endoscopic retrograde cholangiopancreatography
Endoscopic retrograde cholangiopancreatography is a technique that combines the use of endoscopy and fluoroscopy to diagnose and treat certain problems of the biliary or pancreatic ductal systems...
(ERCP) is the most common approach in unblocking the bile duct. This involves endoscopy (passing a fiberoptic tube through the stomach into the duodenum), identification of the ampulla of Vater and insertion of a small tube into the bile duct. A sphincterotomy (making a cut in the sphincter of Oddi) is typically done to ease the flow of bile from the duct and to allow insertion of instruments to extract gallstones that are obstructing the common bile duct
Common bile duct
The common bile duct is a tube-like anatomic structure in the human gastrointestinal tract. It is formed by the union of the common hepatic duct and the cystic duct . It is later joined by the pancreatic duct to form the ampulla of Vater...
; alternatively or additionally, the common bile duct orifice can be dilated with a balloon. Stones may be removed either by direct suction or by using various instruments, including balloons and baskets to trawl the bile duct in order to pull stones into the duodenum. Obstructions that are caused by larger stones may require the use of an instrument known as a mechanical lithotriptor
Lithotriptor
Extracorporeal shock wave lithotripsy is a non-invasive treatment of kidney stones and biliary calculi using an acoustic pulse....
in order to crush the stone prior to removal. Obstructing stones that are too large to be removed or broken mechanically by ERCP may be managed by extracorporeal shock wave lithotripsy. This technique uses acoustic shock waves administered outside the body to break down the stones. An alternative technique to remove very large obstructing stones is electrohydraulic lithotripsy, where a small endoscope known as a cholangioscope is inserted by ERCP to directly visualize the stone. A probe uses electricity to generate shock waves that break down the obstructing stone. Rarely, surgical exploration of the common bile duct (termed choledochotomy), which can be performed with laparoscopy
Laparoscopy
Laparoscopy is an operation performed in the abdomen or pelvis through small incisions with the aid of a camera...
, is required to remove the stone.
Narrowed areas may be bridged by a stent
Stent
In the technical vocabulary of medicine, a stent is an artificial 'tube' inserted into a natural passage/conduit in the body to prevent, or counteract, a disease-induced, localized flow constriction. The term may also refer to a tube used to temporarily hold such a natural conduit open to allow...
, a hollow tube that keeps the duct open. Removable plastic stents are used in uncomplicated gallstone disease, while permanent self-expanding metal stents
Self-expandable metallic stent
A self-expandable metallic stent is a metallic tube, or stent, used in order to hold open a structure in the gastrointestinal tract in order to allow the passage of food, chyme, stool, or other secretions required for digestion...
with a longer lifespan are used if the obstruction is due to pressure from a tumor such as pancreatic cancer
Pancreatic cancer
Pancreatic cancer refers to a malignant neoplasm of the pancreas. The most common type of pancreatic cancer, accounting for 95% of these tumors is adenocarcinoma, which arises within the exocrine component of the pancreas. A minority arises from the islet cells and is classified as a...
. A nasobiliary drain may be left behind; this is a plastic tube that passes from the bile duct through the stomach and the nose and allows continuous drainage of bile into a receptible. It is similar to a nasogastric tube, but passes into the common bile duct directly, and allows for serial x-ray cholangiograms to be done to identify the improvement of the obstruction. The decision on which of the aforementioned treatments to apply is generally based on the severity of the obstruction, findings on other imaging studies, and whether the patient has improved with antibiotic treatment. Certain treatments may be unsafe if blood clotting
Coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...
is impaired, as the risk of bleeding (especially from sphincterotomy) is increased in the use of medication such as clopidogrel
Clopidogrel
Clopidogrel is an oral, thienopyridine class antiplatelet agent used to inhibit blood clots in coronary artery disease, peripheral vascular disease, and cerebrovascular disease. It is marketed by Bristol-Myers Squibb and Sanofi-Aventis under the trade name Plavix. The drug works by irreversibly...
(which inhibits platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
aggregation) or if the prothrombin time
Prothrombin time
The prothrombin time and its derived measures of prothrombin ratio and international normalized ratio are measures of the extrinsic pathway of coagulation. This test is also called "ProTime INR" and "INR PT". They are used to determine the clotting tendency of blood, in the measure of warfarin...
is significantly prolonged. For a prolonged prothrombin time, vitamin K
Vitamin K
Vitamin K is a group of structurally similar, fat soluble vitamins that are needed for the posttranslational modification of certain proteins required for blood coagulation and in metabolic pathways in bone and other tissue. They are 2-methyl-1,4-naphthoquinone derivatives...
or fresh frozen plasma
Fresh frozen plasma
The term fresh frozen plasma refers to the liquid portion of human blood that has been frozen and preserved after a blood donation and will be used for blood transfusion...
may be administered to reduce bleeding risk.
It may be difficult to obtain endoscopic access to the obstruction located higher (proximal) up in the biliary system, or when it is due to a stricture in the priorly performed anastomosis between the bile duct (surgically joining) with the duodenum or jejunum
Jejunum
The jejunum is the middle section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms middle intestine or mid-gut may be used instead of jejunum.The jejunum lies between the duodenum...
. When this happens, percutaneous transhepatic cholangiography
Percutaneous transhepatic cholangiography
Percutaneous transhepatic cholangiography or percutaneous hepatic cholangiogram is a radiologic technique used to visualize the anatomy of the biliary tract. A contrast medium is injected into a bile duct in the liver, after which X-rays are taken...
(PTC) may be needed to relieve pressure. This involves identifying the bile duct by ultrasound and then passing a tube through the skin (percutaneous). PTC is generally performed by radiologists
Radiology
Radiology is a medical specialty that employs the use of imaging to both diagnose and treat disease visualized within the human body. Radiologists use an array of imaging technologies to diagnose or treat diseases...
. PTC has potential complications, so occasionally further attempts at ERCP by more experienced doctors are preferred.
Continual contamination of bile duct by indwelling stents (as may occur in chronic conditions like tumor of the head of pancreas
Head of pancreas
The head of pancreas is a portion of the pancreas that is lodged within the curve of the duodenum, and is flattened anteriorly . The other parts of the pancreas are the body and the tail....
) requires monitoring by repeated radiologic tests and changing of the stents.
Cholecystectomy
Not all gallstones implicated in ascending cholangitis actually originate from the gallbladder, but cholecystectomyCholecystectomy
Cholecystectomy is the surgical removal of the gallbladder. It is the most common method for treating symptomatic gallstones. Surgical options include the standard procedure, called laparoscopic cholecystectomy, and an older more invasive procedure, called open cholecystectomy.-Open surgery:A...
(surgical removal of the gallbladder) is generally recommended in people who have been treated for cholangitis due to gallstone disease. This is typically delayed until all symptoms have resolved and ERCP or MRCP have confirmed that the bile duct is clear of gallstones. Those who do not undergo cholecystectomy have an increased risk of recurrent biliary pain, jaundice, further episodes of cholangitis, and need for further ERCP or related procedures; the risk of death is also significantly increased.
Prognosis
Acute cholangitis carries a significant risk of death, the leading cause being irreversible shock with multiple organ failure (a possible complication of severe infections). Improvements in diagnosis and treatment have led to a reduction in mortality: before 1980, the mortality rate was greater than 50%, but after 1980 it was 10–30%. Patients with signs of multiple organ failure are likely to die unless they undergo early biliary drainage and treatment with systemic antibiotics. Other causes of death following severe cholangitis include heart failure and pneumoniaPneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
.
Risk factors indicating an increased risk of death include older age, female gender, a history of liver cirrhosis
Cirrhosis
Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...
, biliary narrowing due to cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
, acute renal failure
Acute renal failure
Acute kidney injury , previously called acute renal failure , is a rapid loss of kidney function. Its causes are numerous and include low blood volume from any cause, exposure to substances harmful to the kidney, and obstruction of the urinary tract...
and the presence of liver abscess
Liver abscess
A liver abscess is a pus-filled mass inside the liver. Common causes are abdominal infections such as appendicitis or diverticulitis due to haematogenous spread through the portal vein...
es. Complications following severe cholangitis include renal failure, respiratory failure
Respiratory failure
The term respiratory failure, in medicine, is used to describe inadequate gas exchange by the respiratory system, with the result that arterial oxygen and/or carbon dioxide levels cannot be maintained within their normal ranges. A drop in blood oxygenation is known as hypoxemia; a rise in arterial...
(inability of the respiratory system to oxygenate blood and/or eliminate carbon dioxide), cardiac arrythmia, wound infection, pneumonia
Pneumonia
Pneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
, gastrointestinal bleeding
Gastrointestinal bleeding
Gastrointestinal bleeding or gastrointestinal hemorrhage describes every form of hemorrhage in the gastrointestinal tract, from the pharynx to the rectum. It has diverse causes, and a medical history, as well as physical examination, generally distinguishes between the main forms...
and myocardial ischemia
Myocardial ischemia
Myocardial ischemia is an imbalance between myocardial oxygen supply and demand. Left untreated, it results in angina pectoris, myocardial stunning, myocardial hibernation, ischemic preconditioning, postconditioning, or under the most severe instances, acute coronary syndrome and myocardial...
(lack of blood flow to the heart, leading to heart attacks
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
).
Epidemiology
In the Western world, about 15% of all people have gallstones in their gallbladder but the majority are unaware of this and have no symptoms. Over ten years, 15–26% will suffer one or more episodes of biliary colicBiliary colic
Biliary colic is pain associated with irritation of the viscera secondary to cholecystitis and gallstones. Unlike renal colic, the phrase 'biliary colic' refers to the actual cholelithiasis....
(abdominal pain due to the passage of gallstones through the bile duct into the digestive tract), and 2–3% will develop complications of obstruction: acute pancreatitis
Acute pancreatitis
Acute pancreatitis or acute pancreatic necrosis is a sudden inflammation of the pancreas. It can have severe complications and high mortality despite treatment...
, cholecystitis
Cholecystitis
-Signs and symptoms:Cholecystitis usually presents as a pain in the right upper quadrant. This is known as biliary colic. This is initially intermittent, but later usually presents as a constant, severe pain. During the initial stages, the pain may be felt in an area totally separate from the site...
or acute cholangitis. Prevalence of gallstone disease increases with age and body mass index
Body mass index
The body mass index , or Quetelet index, is a heuristic proxy for human body fat based on an individual's weight and height. BMI does not actually measure the percentage of body fat. It was invented between 1830 and 1850 by the Belgian polymath Adolphe Quetelet during the course of developing...
(a marker of obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
). However, risk is also increased in those who lose weight rapidly (e.g. after weight loss surgery
Bariatric surgery
Bariatric surgery includes a variety of procedures performed on people who are obese. Weight loss is achieved by reducing the size of the stomach with an implanted medical device or through removal of a portion of the stomach or by resecting and re-routing the small intestines...
) due to alterations in the composition of the bile that makes it prone to form stones. Gallstones are slightly more common in women than in men, and pregnancy increases the risk further.
History
Dr Jean-Martin CharcotJean-Martin Charcot
Jean-Martin Charcot was a French neurologist and professor of anatomical pathology. He is known as "the founder of modern neurology" and is "associated with at least 15 medical eponyms", including Charcot-Marie-Tooth disease and amyotrophic lateral sclerosis...
, working at the Salpêtrière Hospital
Pitié-Salpêtrière Hospital
The Pitié-Salpêtrière Hospital is a teaching hospital located in Paris, France. Part of the Assistance publique - Hôpitaux de Paris, it is one of Europe's largest hospitals...
in Paris, France, is credited with early reports of cholangitis, as well as his eponymous triad, in 1877. He referred to the condition as "hepatic fever" (fièvre hépatique). Dr Benedict M. Reynolds, an American surgeon, reignited interest in the condition in his 1959 report with colleague Dr Everett L. Dargan, and formulated the pentad that carries his name. It remained a condition generally treated by surgeons, with exploration of the bile duct and excision of gallstones, until the ascendancy of ERCP in 1968. ERCP is generally performed by internal medicine or gastroenterology specialists. In 1992 it was shown that ERCP was generally safer than surgical intervention in ascending cholangitis.
See also
- Primary sclerosing cholangitisPrimary sclerosing cholangitisPrimary sclerosing cholangitis is a chronic liver disease caused by progressive inflammation and scarring of the bile ducts of the liver. The inflammation impedes the flow of bile to the gut, which can ultimately lead to liver cirrhosis, liver failure and liver cancer...
(an autoimmune diseaseAutoimmune diseaseAutoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
leading to narrowing of the bile ducts) - Gallstone-related pancreatitis