Gallbladder Pain: Cholelithiasis vs Cholecystitis vs Cholangitis
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Example Case
A female patient presents with right upper quadrant abdominal pain for the past 2 days. Today she developed a fever along with nausea, and she tells you that she noticed her eyes appeared more yellow.
She reports a known history of gallstones identified on an outpatient ultrasound 6 months ago. Her symptoms at that time had subsided and she elected not to undergo any further treatment.
Cholelithiasis, cholecystitis, choledocholithiasis, and cholangitis are all in your differential, and you are trying to decide what your next management steps will include.
Introduction
When learning about the gallbladder and biliary system, the terms cholelithiasis, cholecystitis, choledocholithiasis, and cholangitis sound similar yet are very different disease states.
Let’s walk through each one step by step using illustrations and strategies that will help clarify the pathology.
Biliary Anatomy
Let’s first start with the biliary anatomy as this will help to visualize and understand the underlying processes for each of the biliary diseases that will be discussed below.
The gallbladder is located inferior to the liver and stores bile that is secreted by the liver.
Bile aids in the digestion of fats and primarily consists of cholesterol, bile salts, and bilirubin.
Bile exits the liver through the right and left hepatic ducts which converge to form the common hepatic duct.
The gallbladder connects to the common hepatic duct via the cystic duct.
Together the cystic duct and common hepatic duct form the common bile duct which then travels inferiorly, through the pancreatic head, and terminates in the duodenum at the ampulla of Vater.
Approximately half of the bile produced by the liver will travel directly to the duodenum to assist with digestion of fats. The remainder of the bile produced by the liver will be stored in the gallbladder.
Shortly after consuming a meal, the gallbladder will contract to release the stored bile to assist with digestion.
Gastrointestinal Anatomy
Zoomed in image of above picture focusing on anatomy of liver, gallbladder, and biliary system.
I created this sketch that we will use to help describe each of the gallbladder and biliary diseases. You can see that bile is released by the liver. Some of the bile is stored in the gallbladder while some of it travels into the duodenum to assist with digestion of food content. Pancreatic enzymes are also released into the duodenum to assist with digestion.
Cholelithiasis
The underlying pathology for cholelithiasis, cholecystitis, choledocholithiasis, and cholangitis can be understood by breaking down each of the words.
Let’s start with cholelithiasis.
Chole = Gall/Bile
Lithiasis = Stone
Cholelithiasis = Gallstones
The term “chole” means “gall” or “bile” and usually relates to the gallbladder or biliary system.
We know from our medical terminology lecture that “lithiasis” means “stone” or the formation/presence of stony concretions.
Therefore, cholelithiasis is the formation or presence of gallstones, usually in the gallbladder.
Simply put…..cholelithiasis means gallstones.
As mentioned above, the liver releases concentrations of cholesterol, bile salts, and bilirubin in the form of bile to assist with digestion of fats.
Formation of gallstones occurs when any of these substances that make up the bile are present in large concentrations.
As the bile becomes more concentrated in the gallbladder, sludge may form.
The continued aggregation of sludge can lead to the formation of stones, or cholelithiasis.
Cholesterol gallstones are the most common type of gallstones followed by calcium and bilirubin.
Risk factors for cholelithiasis are obesity, hyperlipidemia, pregnancy, female sex, European or Native American ancestry, and age.
Obesity, hyperlipidemia, and diabetes are all associated with increased hepatic cholesterol secretion which increases the risk for cholelithiasis.
Pregnancy is also a risk factor as progesterone can lead to decreased gallbladder contractility. This results in stasis of bile which can lead to formation of biliary sludge and stones.
Progesterone levels are increased during pregnancy thereby making pregnancy or history of multiple pregnancies a risk factor.
The risk factors for cholelithiasis can be remembered using the 5 F’s: Female, Fat, Forty, Fertile, and Foreign.
Cholelithiasis Risk Factors: The 5 F’s
Female
Fat
Forty
Fertile
Foreign
Many people live with gallstones and never have any symptoms.
Gallstones create a problem when they become lodged anywhere in the outflow tract, which will be the focus of the remaining biliary diseases discussed below.
Patient’s with cholelithiasis may experience right upper quadrant pain if a gallstone temporarily moves into the cystic duct.
The pain will then subside if and when the gallstone moves back into the gallbladder thereby eliminating the outflow obstruction.
This intermittent right upper quadrant pain from cholelithiasis is called biliary colic and is caused by intermittent obstruction of the cystic duct by a gallstone(s).
Typically the pain occurs after eating a meal. Consuming food triggers the gallbladder to contract to release bile to aid in digestion of fats.
Gallbladder contraction can move gallstones into the cystic duct leading to right upper quadrant abdominal pain and biliary colic.
Cholithiasis can be diagnosed using a right upper quadrant ultrasound that will show hyperechoic stony formations with a posterior acoustic shadow.
Cholelithiasis may not cause any symptoms, and can usually be managed outpatient if it does.
If symptoms of biliary colic become persistent or impede the patient from living a quality of life, then an outpatient elective cholecystectomy can be performed.
Cholelithiasis pictured above: Gallstones residing in the gallbladder. The patient may be asymptomatic or have biliary colic. Diagnosis: Right upper quadrant ultrasound. Treatment: Outpatient management, possible elective cholecystectomy.
Cholecystitis
Let’s first break down the word like we did with cholelithiasis!
This will help us understand the underlying pathology.
Chole = Gall/Bile
Cyst = Bladder
Cholecyst = Gallbladder
Itis = Inflammation
Cholecystitis = Inflammation of the Gallbladder
We know from above that “chole” means “gall” or “bile”.
We also know from our medical terminology lecture on root words that “cyst” means bladder.
So if we put “chole” and “cyst” together, then we have “cholecyst” which means gallbladder!
Easy, right!
We know from our medical terminology lecture on suffixes that “itis” means inflammation.
Therefore, when we put the word cholecystitis together it refers to inflammation of the gallbladder.
Cholecystitis occurs when a gallstone obstructs the cystic duct and causes gallbladder outflow obstruction.
As mentioned above, the gallstone may move into the cystic duct temporarily before moving back into the gallbladder causing biliary colic and intermittent right upper quadrant abdominal pain.
In the case of cholecystitis, however, the gallstone has remained in the cystic duct long enough to cause persistent obstruction. (There are cases of acalculous cholecystitis but this is less common and not the focus of this post).
The presence of a gallstone in the cystic duct can lead to outflow obstruction of the proximal structures including the gallbladder and the portion of the cystic duct up to the stone.
The remaining bile and contents in the gallbladder are now static from obstruction and become a breeding ground for bacteria and infection.
Inflammation and/or infection eventually develops leading to cholecystitis.
Symptoms may include right upper quadrant pain, nausea/vomiting, and fever.
On physical exam, the patient may have a positive Murphy sign.
In order to perform the Murphy test, palpate the inferior border of the patient’s liver.
Then ask the patient to take in a deep breath.
During inspiration, the diaphragm moves the liver/gallbladder inferiorly where the hand is palpating. A positive Murphy sign is cessation of inspiration due to pain.
Murphy Sign
Palpate inferior border of liver
Ask patient to inhale
Cessation of inspiration due to pain = + Murphy Sign
The work up and approach to upper abdominal pain may include blood tests such as CBC, chemistry, LFTs, lipase, lactate, blood cultures, and pregnancy if applicable.
Make sure to consider intrathoracic etiologies such as troponin (ACS) or d-dimer (PE) if applicable as the patient may not always experience classic chest pain.
For a simple mnemonic to remember the main causes of upper abdominal pain check out the following EZmed post! “The UPPER STOMACH Mnemonic”.
The initial imaging modality of choice when concerned for gallbladder pathology is a right upper quadrant ultrasound.
Findings of cholecystitis on ultrasound include pericholecystic fluid (fluid around the gallbladder), gallbladder wall thickening, potential presence of gallstones, and positive sonographic Murphy sign.
While CT abdomen can sometimes diagnose acute cholecystitis as well, right upper quadrant ultrasound remains the preferred imaging of choice.
I have attached a couple papers discussing CT to diagnose acute cholecystitis at the bottom of this post. Some of these studies had small population and sample sizes, but still interesting to read.
If the ultrasound is equivocal and suspicion for cholecystitis remains high, then a HIDA scan can be performed.
Radioactive tracer is injected intravenously and then observed as it travels through the biliary system.
No radioactive tracer seen in the gallbladder could indicate cystic duct obstruction, inflammation, and/or cholecystitis.
HIDA scan may not demonstrate the complications of cholecystitis or alternative diagnoses like the ultrasound can. Therefore, ultrasound is still the preferred initial modality, and HIDA scan is reserved for when the ultrasound is equivocal.
Treatment includes antibiotics and cholecystectomy.
Cholecystitis pictured above: A gallstone is obstructing the cystic duct causing inflammation of structures proximally. Symptoms: Right upper quadrant abdominal pain, fever, nausea, vomiting. There may be a positive Murphy sign on examination. Diagnosis: Ultrasound or HIDA scan. Treatment: Antibiotics and cholecystectomy.
Choledocholithiasis
The next gallbladder disease to discuss is choledocholithiasis.
Let’s break down the word again!
Choledocho = Common Bile Duct
Lithiasis = Stone
Choledocholithiasis = Presence of stones (usually gallstones) in the common bile duct
“Choledocho” refers to the “common bile duct”.
We know from above that “lithiasis” means “stone”.
Therefore, choledocholithiasis is the presence of stones (usually gallstones) in the common bile duct.
Similar to the presence of a stone in the cystic duct, the patient can experience right upper quadrant pain.
The differences in anatomical location of the gallstone in cholelithiasis versus choledocholithiasis is important as it can lead to changes in the patient’s presentation, blood work, and imaging.
When a stone is intermittently obstructing the cystic duct, the gallbladder is the only organ/structure proximal to that stone.
However, a stone obstructing the common bile duct over time will impact the outflow of both the liver and gallbladder.
As a result, choledocholithiasis can lead to jaundice on physical exam from hepatic outflow obstruction of bilirubin.
The patient may also have abnormal liver function tests and elevated bilirubin levels on blood work.
Diagnostic workup includes labs mentioned above and imaging.
Right upper quadrant ultrasound, although not quite as sensitive and specific as it is for cholelithiasis and cholecystitis, can again be used to assess for choledocholithiasis.
Choledocholithiasis on ultrasound may be evidenced by common bile duct dilation, presence of gallstones in the common bile duct, and presence of gallstones in the gallbladder as this increases suspicion that there could be a stone in the common bile duct.
The presence of a gallstone in the common bile duct can be difficult to appreciate on right upper quadrant ultrasound.
Therefore, if clinical suspicion remains high despite unremarkable ultrasound, then ERCP and MRCP both have higher sensitivities and specificities than ultrasound.
They are the gold standard for diagnosing choledocholithiasis.
CT imaging again has moderate sensitivity and specificity and the other imaging modalities discussed should be considered first.
Furthermore, ERCP is not only diagnostic but also therapeutic. It uses endoscopic techniques to diagnose choledocholithiasis which can then be treated with endoscopic sphincterotomy and/or stone removal.
Choledocholithiasis pictured above: Gallstone obstructing the common bile duct. Symptoms: right upper quadrant pain, nausea, vomiting, jaundice. Liver function tests and bilirubin levels may be elevated. Diagnosis: Ultrasound, ERCP, or MRCP. Treatment: ERCP.
Cholangitis
The final disease state that will be discussed is cholangitis.
You know the drill….let’s break down the word!
Chole = Bile/Gall
Angio = Ducts/Vessels
Cholangio = Bile Ducts
Itis = Inflammation
Cholangitis = Inflammation of the Bile Ducts
We know “chole” means “bile” or “gall”.
We also know from our medical terminology lecture that “angio” means vessels or ducts.
So if we put “chole” and “angio” together, then we have bile ducts!
We also know from above that “-itis” means inflammation.
Therefore, cholangitis refers to inflammation of the bile ducts which can also lead to infection.
Cholangitis is typically caused by some kind of obstruction of the common bile duct/biliary system.
This is commonly due to an obstructed gallstone in the common bile duct.
However, cancer of the pancreatic head can also lead to obstruction of the common bile duct and a similar patient presentation.
Similar to how an obstructive gallstone in the cystic duct for a prolonged period of time can lead to gallbladder inflammation from stasis of material, prolonged obstruction of the common bile duct from a stone can also lead to inflammation/infection.
The difference, however, is that the gallbladder is the only structure involved in cholecystitis since the obstruction is in the cystic duct, whereas all the structures proximal to a stone obstructing the common bile duct could be involved. This can include the gallbladder, liver, and biliary system.
Cholangitis is also referred to as ascending cholangitis for this reason; biliary outflow is obstructed and inflammation occurs proximal to the obstruction in an ascending fashion.
When the gallbladder, liver, and biliary system become inflamed and possibly infected this can lead to symptoms of right upper quadrant abdominal pain, fever, jaundice, nausea, and vomiting.
Charcot’s Triad is used to describe the symptoms and presentation seen with cholangitis and includes fever, right upper quadrant pain, and jaundice.
Reynold’s pentad may also be seen in cholangitis and includes Charcot’s triad plus hypotension and altered mental status.
Charcot’s Triad in Cholangitis
Fever
RUQ Pain
Jaundice
Reynold’s Pentad in Cholangitis
Charcot’s Triad
Altered Mental Status
Hypotension
Diagnostic tests again include the labs above and imaging.
The imaging approach is similar to that of choledocholithiasis as the pathology is similar.
Cholangitis is essentially a sequela or progression of choledocholithiasis.
Right upper quadrant ultrasound may show bile duct dilatation or the presence of a stone in the common bile duct.
ERCP and MRCP are more sensitive and specific, and ERCP is also therapeutic as described above.
Cholecystectomy is usually performed concomitantly.
Mortality rate can be high with cholangitis, and it is important patient’s receive appropriate care with IV antibiotics and fluids as well.
Cholangitis pictured above: Obstructive gallstone in common bile duct causing inflammation of structures proximally. Symptoms, fever, right upper quadrant pain, jaundice, altered mental status, nausea/vomiting. Diagnosis: Labs, right upper quadrant ultrasound, ERCP, MRCP. Treatment: Antibiotics, ERCP, cholecystectomy.
Lithiasis = Stone
Cholelithiasis = Gallstones, usually in gallbladder (Chole = Gall)
Choledocholithiasis = Gallstones in CBD (Choledocho = CBD)
Itis = Inflammation
Cholecystitis = Gallbladder inflammation (Cholecyst = Gallbladder)
Cholangitis = Bile duct inflammation (Cholangio = Bile Ducts)
Conclusion
Hopefully this helped delineate the pathology of cholelithiasis, cholecystitis, choledocholithiasis, and cholangitis.
If you found the content useful, please leave a comment down below or provide any other suggestions!
Below is a summary of the different gallbladder diseases discussed and applied to the anatomical image shown at the beginning of the post.
I have also created a table that summarizes everything discussed.
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US vs CT imaging modality articles
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082629/
https://www.ncbi.nlm.nih.gov/pubmed/26375322
https://pubs.rsna.org/doi/full/10.1148/radiol.12111561