Introduction
Gallstones (also known as cholelithiasis) are hardened remnants of bile that can form and collect in your gallbladder. Most gallstones are asymptomatic despite their high prevalence and are discovered incidentally. Symptomatic cases present following obstruction and/or inflammation of the biliary tract, including biliary colic, cholecystitis, ascending cholangitis and pancreatitis.
Epidemiology
Gallstones are common in adults and can affect between 5-25% of adults, especially women and older adults.
Basic anatomy
The gallbladder is a small sac located behind the liver and serves to store the bile that your liver produces continuously.
Once chyme passes from the stomach into the duodenum, bile is squeezed out via the biliary tree and into the duodenum. Biles consists of water, cholesterol, bile acids, electrolytes, phospholipids and conjugated bilirubin. The primary purpose of bile is to facilitate digestion by providing optimal pH and emulsion for the enzymatic activity. Another use of bile is a means for the body to excrete bilirubin.
Risk factors
There are both modifiable and non-modifiable risk factors for developing gallstones.
| Modifiable risk factors | Non-modifiable risk factors |
|---|---|
| 1. Rapid weight loss 2. Obesity 3. Sedentary behaviour 4.Smoking 5. Total parenteral nutrition 6. Diet: – High calorie – Low fibre – Highly absorbable sugars 7. Medication: – Oestrogen – Octreotide – Ceftriaxone 8.Medical conditions: – Haemolytic conditions – Hypertriglyceridaemia – Cirrhosis – Cystic fibrosis – Ileal diseases – Bacterial or parasitic infections – Neoplasms | 1. Older age 2. Female 3. Genetic factors/family history |
A commonly used aide memoire for remembering the main risk factors for gallstones is ‘5 Fs’:
- Female sex
- Fair: Caucasian ethnicity
- Fat: BMI >30
- Fertile: had one or more children
- Forty: age over 40 years
Pathophysiology
Gallstones form through three main pathways: cholesterol supersaturation, bilirubin excess and gallbladder motility/contractility defects.
Cholesterol supersaturation
When the liver produces more cholesterol than the bile can dissolve, the extra cholesterol will eventually precipitate as crystals. These crystals become trapped within the gallbladder and eventually accumulate and grow into gallstones.
Bilirubin excess
Excess excretion of bilirubin, a metabolic by-product of normal haem breakdown, may also cause stone formation. This is exacerbated by conditions that increase haem breakdown and its excretion into bile. The excess will eventually crystallize and form gallstones as well.
Gallbladder motility and contractility
Conditions or defects that stop the gallbladder from fully emptying may lead to the concentration of bile, leading to gallstone formation.
Gallstone types
Most gallstones in developed countries are cholesterol gallstones (85%). However, other types are more common in the rest of the world.
In developing countries, pigmented stones are more common due to the prevalence of bacterial infections, biliary parasites and stasis. Pigmented stones in developed countries tend to occur due to stasis, often as a result of inflammatory biliary diseases or neoplasms, such as primary sclerosing cholangitis and cholangiocarcinoma.
| Type | Composition | Prevalence | Specific risk factors | Radiological findings |
|---|---|---|---|---|
| Cholesterol gallstone | Bile supersaturated with cholesterol, at least 90% cholesterol | 37-86% of all gallstones | High cholesterol intake or depleted bile salts | Radiolucent on x-ray |
| Pigmented gallstone (brown or black) | Black gallstones are mostly made of bilirubin. Brown stones may also contain calcium salts of fatty acid, cholesterol and mucin | 2-27% of all gallstones | Haemolytic diseases | Radiolucent on x-ray |
| Calcium gallstone | Calcium | 1-17% of all gallstones | General gallstone risk factors | Radiopaque on x-ray |
| Mixed gallstone | Mixture of cholesterol, bilirubin and calcium salts | 4-16% of all gallstones | General gallstone risk factors | Radiological features depend on the calcium content of the stone, with more calcium increasing its opacity on x-ray |
Clinical features
The majority of gallstones (90%) are asymptomatic. People usually begin experiencing symptoms when gallstones produce inflammation, obstruct the biliary tree and/or migrate to other organs.
Biliary colic: Uncomplicated gallstone disease
Uncomplicated gallstone disease refers to biliary colic in the absence of associated complications, such as cholecystitis, ascending cholangitis and gallstone pancreatitis. In other words, uncomplicated gallstone disease presents with pain only and has no features of inflammation.
Biliary colic is caused by obstruction of the cystic duct or, less frequently, the common bile duct (also known as choledocholithiasis). This usually presents with acute abdominal pain characterised by:
- Site: Usually upper right quadrant pain and tenderness
- Onset: Episodic pain that usually self-resolves. Note that biliary colic is not ‘true colic’ as pain intensity does not fluctuate following onset
- Timing: Pain lasts from minutes to hours
- Radiation: may radiate to the back
- Associated factors: often triggered by/after eating
- Severity: Constant and severe abdominal pain.
Nausea may also present alongside abdominal pain. In common bile duct obstructions, obstructive jaundice may also occur.
Complicated gallstone disease
It is important to also recognise signs of complicated gallstone diseases such as cholecystitis, ascending cholangitis and gallstone pancreatitis. Unlike those with biliary colic, these patients may deteriorate quickly and may need urgent medical or surgical attention. They may present with:
- Prolonged right upper quadrant pain
- Unstable observations:
- Tachycardia
- Tachypnoea
- Hypotension
- Hypoxia
- Pyrexia
- Reduced consciousness/GCS score
- Central abdominal pain
- Bruising of central abdomen or the flanks
Investigations
Blood tests
| Investigation | Findings |
|---|---|
| Serum Liver Function Tests (LFT) | Normal in uncomplicated cholelithiasis Alkaline phosphatase (ALP), bilirubin and alanine aminotransferase (ALT) may be raised in common bile duct obstructions |
| Full Blood Count | Elevated white cell count may indicate active inflammation or infection and can be suggestive of complications |
| Serum lipase & amylase | If elevated above 3x normal amounts, suggests acute pancreatitis. Otherwise, can be used to exclude pancreatitis |
Imaging
As most gallstones are radiolucent, the gold-standard investigation is abdominal ultrasound. Further imaging investigations revolve largely around modern technology like Magnetic Resonance Cholangiopancreatography (MRCP), whereas Endoscopic Retrograde Cholangiopancreatography (ERCP) is predominantly reserved for therapeutic objectives and Computer Tomography (CT) is used to look for intra-abdominal complications.
| Investigation | Findings |
|---|---|
| Abdominal ultrasound | Can detect gallstones and bile duct dilatation with a high sensitivity and specificity. |
| MRCP | Identify stones in gallbladder and biliary tree |
| ERCP | Although can be used for imaging, its primary role is for therapeutic procedures given its risk of causing pancreatitis |
| Abdominal CT scan | Normal in uncomplicated disease Can detect presence of gallstones, biliary tree dilatation and pancreas involvement |
Management
The management of gallstones depends on the patient’s presentation and can range from not intervening to surgical interventions.
Asymptomatic gallstones
Gallstones are often identified incidentally as part of other investigations and should not be treated if both gallbladder and biliary tree are healthy.
The vast majority of asymptomatic gallstones do not require treatment. Certain patient groups (such as those with porcelain gallbladder) may be offered prophylactic cholecystectomy if at high risk of gallstone disease or gallbladder carcinoma.
Uncomplicated symptomatic gallstones
Treat biliary colic with simple analgesics, such as non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol. Severe symptoms may be alleviated by opioids. Patients with symptomatic gallstone should be offered laparoscopic cholecystectomy, which is usually done as an elective procedure.
Complicated symptomatic gallstones
The underlying cause should be treated. Options may range from conservative/medical to surgical operations depending on the complication and may include emergency cholecystectomy.
Complications
Apart from biliary colic, gallstones can also lead to:
- Cholecystitis
- Ascending cholangitis
- Pancreatitis
- Empyema of the gallbladder
- Fistula formation between gallbladder to duodenum or colon
- Gallstone ileus (as a result of a gallstone obstructing bowels following fistula formation and migration)
- Mirizzi’s syndrome: gallstone lodged in cystic duct or at the neck of the gallbladder can apply pressure on the common hepatic duct, producing obstructive jaundice
- Cholangiocarcinoma
References
- https://www.bmj.com/bmj/section-pdf/755948?path=/bmj/348/7955/Clinical_Review.full.pdf
- https://www.ncbi.nlm.nih.gov/books/NBK470440/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899548/
- https://bestpractice.bmj.com/topics/en-gb/3000206
- https://www.sciencedirect.com/topics/medicine-and-dentistry/cholesterol-stone
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899548/
- https://pmj.bmj.com/content/77/906/221
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