Gallstones

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Published: November 24, 2017
Last reviewed: December 5, 2017

What are gallstones?

Gallstones are hardened clumps of saturated bile that can appear in the gallbladder or bile ducts. The medical term for gallstones is cholelithiasis.

The gallbladder is a small sac that lies underneath the liver, under the lower edge of the rib cage on the right side (Picture 1).

Gallbladder and bile ducts

Picture 1. The gallbladder and bile ducts 

The bile ducts carry the bile from the gallbladder into the small intestine. The bile, which consists of water, bile salts, bilirubin and cholesterol, helps to digest fat.

Gallstone size can range from 2 mm to more than 4 cm [9]. You can have a single or multiple gallstones.

Gallstone Types

There are 3 main types of gallstones:

  • Cholesterol gallstones, the most common type in the Western world contain at least 70% of cholesterol; they are yellow-green, brown or white. They are not visible on an X-ray.
  • Pigment gallstones are made mainly of bilirubin and <30% cholesterol; they are dark [10,11].
    • Black pigment gallstones are compounds of calcium and bilirubin (calcium bilirubinate). They form as a result of decreased gallbladder motility (in prolong fasting or intravenous feeding), breakdown of red blood cells (chronic hemolysis; in sickle cell disease), liver cirrhosis, cystic fibrosis, ileal disease or after surgery. They tend to remain in the gallbladder and rarely pass into the bile ducts.
    • Brown gallstones consist of unconjugated bilirubin, calcium salts of fatty acids and small amount of cholesterol (<10%) and protein. They tend to appear in the infected bile ducts (rarely in the gallbladder) as a complication of strictures or parasites, mainly in Asian populations [14]. They are usually visible on an X-ray.
  • Mixed gallstones contain cholesterol (30-70%), calcium bilirubinate or carbonate, protein and bile salts [11,13]

Rarely, gallstones have calcium carbonate or phosphate, cystine, proteins or fatty acids as the main component [13].

Gallstone Symptoms and Signs

In most cases, gallstones do not cause any problems.

You can have stones in the gallbladder for decades without having pain. When a stone moves toward the exit of the gallbladder or further into the cystic or common bile duct, it can obstruct the bile flow, which results in the gallbladder distension and pain.

Symptoms of gallstones in the gallbladder without inflammation [1,4]:

  • Sudden, constant pain in the upper right abdominal quadrant, which typically lasts 1-5 hours (range: 30 minutes to 12 hours); the pain is recurrent; it can appear every few days, months or years; there is no pain or other symptoms between the attacks.
  • No or mild tenderness in the upper right abdominal quadrant
  • Nausea or vomiting, which can occur during but not between painful episodes
  • Usually no fever

Symptoms of gallstones in the common bile duct (choledocholithiasis) [1,4,6,7,8]:

  • Pain in the right upper abdominal quadrant lasting from several hours to days
  • Jaundice
  • Dark urine and pale stools
  • Fever and chills (in case of bile duct infection – cholangitis)

Causes, Risk Factors and Mechanism

Gallstones can develop when the gallbladder empties slowly or when the bile contains too much cholesterol or bilirubin or not enough bile salts [9].

Risk factors for cholesterol gallstones include [2,3,9,14]:

  • Family history of gallstones
  • Ethnicity [10]: It is estimated that 10-15% of adults in the US have gallstones. Masai people in West Africa seem to have no gallstones, while 70% of Pima Indian women in Arizona have them. In general, gallstones rarely appear in Asians, and commonly in Hispanic and Mexican Americans and North Europeans.
  • Female sex associated with increased levels of the hormone estrogen or progesterone, especially during pregnancy, hormone replacement therapy or taking oral contraceptives
  • Age >40
  • Truncal obesity, especially if associated with diabetes mellitus type 2, high blood pressure, high blood glucose levels, increased blood triglyceride levels (all together known as metabolic syndrome)
  • Sedentary lifestyle 
  • Excessive calorie intake and diet high in refined carbohydrates and low in fiber (white bread, white rice, sugars)
  • Rapid weight loss (>3 pounds/week), especially after bariatric surgery, prolonged fasting, starvation or intravenous nutrition
  • Crohn’s disease, celiac disease, lymphoma that affect the last part of the small intestine (ileum)
  • Low blood HDL cholesterol and high triglyceride levels [14]
  • Medications: oral contraceptives, estrogen replacement therapy, fibrates (fenofibrate, gemfibrozil), thiazide diuretics (chlorothiazide, metolazone), octreotide
  • Transplantation of the heart, lung, kidney or pancreas.

Risk factors for black pigment stones [3,9,12]:

  • Hemolysis – increased breakdown of red blood cells:
    • In children with genetic diseases of the red blood cells: sickle cell disease, spherocytosis, beta-thalassemia
    • In liver cirrhosis (in alcoholics) associated with enlarged spleen
  • Gilbert syndrome
  • Pancreatitis

Risk factors for brown pigment stones [3,9,12]:

  • Cholangitis – infection of the bile ducts by bacteria that come from the intestine due to duodenal diverticles
  • Infestation with bile flukes (in East Asia)

There seems to be no clear connection between the type of diet and gallstones.

Complications

Complications of gallstones can include [11]:

  • Gallbladder inflammation (cholecystitis)
  • Acute pancreatitis
  • Infection of the common bile duct (cholangitis)
  • Obstruction of the cystic or common bile duct (choledocholithiasis)
  • Gallbladder cancer
    • Less than 1% of individuals with gallstones (but greater % of those with family history of gallstones) develop gallbladder cancer; 75-90% of individuals with gallblader cancer has gallstones [15,16].

Gallstones During Pregnancy

During pregnancy, the gallbladder empties slower, so it is more prone to develop gallstones, especially in women who had gallbladder disease before pregnancy. When surgery during pregnancy is required, it should be preferably done in the second trimester; both open and endoscopic surgery are considered safe [5].

Gallstones in Children

Gallstones in children are rare; risk factors include hemolytic anemia (for example, in sickle cell disease), obesity, Crohn’s disease, surgical removal of the last part of the intestine (ileum) and prolonged fasting or artificial feeding [14]. Gallstones in children may resolve on their own in 17% [14].

Diagnosis

If you have gallstones without gallbladder inflammation, a doctor will often find no signs during physical examination. In gallbladder inflammation, you may feel pain when a doctor applies pressure below your rib cage on the right side, especially when breathing in (Murphy’s sign).

In uncomplicated gallstones, liver function tests are usually normal.

Ultrasound can detect all types of gallstones in the gallbladder as small as.??.but only some stones in the cystic or common bile duct.

Gallstones - an ultrasound image

Picture 1. Gallstones – an ultrasound image
(source: Radiopedia, CC license)

Endoscopic ultrasound can reveal gallstones in the cystic duct.

Computed tomography (CT) can show only calcified gallstones and complications, such as gallbladder perforation or abscess.

Oral cystography involves an ingestion of a contrast substance that is secreted into the bile and can reveal the presence of gallstones in the gallbladder or bile ducts.

Endoscopic retrograde cholangiography (ERCP) involves an insertion of an endoscope through the mouth into the duodenum and instillation of a contrast substance into the bile and pancreatic duct. The procedure can reveal gallstones in the bile duct and enables their removal.

Magnetic resonance cholangiopancreatography (MRCP) involves an ingestion of a contrast substance followed by MRI. It is used mainly to check for gallstones in the bile ducts.

Cholescintigraphy (HIDA scan) involves an intravenous injection of a radioactive substance that is secreted into the bile. The scan can reveal gallstones in the cystic and common bile duct and enables evaluation of the gallbladder function.

Treatment

Gallbladder pain is treated by painkillers.

The recommended therapy for recurrent gallbladder attacks is a surgical gallbladder removal.

Extracorpeal shock wave lithotripsy (ESWL) uses high energy sound waves to break stones in small pieces that can be then naturally secreted from the gallbladder into the intestine. It can be used in individuals who have 3 or less noncalcified cholesterol stones in the gallbladder and no stones in the bile ducts [10].

Oral dissolution of gallstones, which involves taking tablets of ursodeoxycholic acid for several months, is intended for treatment of cholesterol gallstones in individuals who do not want or cannot undergo gallbladder removal.

Contact dissolution of gallstones, which involves instillation of a solvent through a catheter inserted into the gallbladder through the abdominal wall, can completely dissolve cholesterol gallstones of any size within several hours to few days.

Gallstones in the Biliary Duct (Choledocholithiasis)

The blockage of the common bile duct (Picture 1) by gallstones can result in [1,4,6,7,8]:

  • Pain in the right upper abdominal quadrant lasting from several hours to days
  • Jaundice
  • Dark urine and pale stools
  • Fever and chills (in case of bile duct infection – cholangitis)

Diagnosis and treatment are by endoscopic retrograde cholangiopancreatography (ERCP).

  • References

      1. Gallstones  Merck Manuals Home Edition
      2. Acute Cholecystitis and Biliary Colic  Emedicine
      3. Gallstones (Cholelithiasis)  Emedicine
      4. Gallstones (Cholelithiasis), Clinical Presentation  Emedicine
      5. Abuabara SF et al, 1997, Laparoscopic cholecystectomy during pregnancy is safe for both mother and fetus  PubMed
      6. Acute Cholangitis, Clinical Presentation  Emedicine
      7. Cholangitis, Clinical Presentation  Emedicine
      8. Notash AY et al, 2008, Preoperative clinical and paraclinical predictors of choledocholithiasis  PubMed
      9. Gallstones  NIDDK
      10. Gallstone disease  John Hopkins Medicine
      11. Borzellino G et al, 2008, Biliary lithiasis Springer Link
      12. Trotman BW, 1991, Pigment gallstone disease  PubMed
      13. Quiao T et al, 2013, The Systematic Classification of Gallbladder Stones  PubMed Central
      14. Stinton LM et al, 2012, Epidemiology of Gallbladder Disease: Cholelithiasis and Cancer PubMed Central
      15. Gallbladder cancer risk factors  Cancer.net
      16. Gallbladder cancer  CancerResearch UK

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