Causes and Risk Factors of Gallbladder Disease

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The term "gallbladder disease" describes any health problem that affects the gallbladder.

While the most common cause of gallbladder disease is gallstones (called cholelithiasis), there are a number of other causes, including gallbladder inflammation (called cholecystitis), biliary dyskinesia, functional gallbladder disease, primary sclerosing cholangitis, and gallbladder cancer.

gallbladder disease causes and risk factors
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Common Causes

Gallstones are the most common manifestation of gallbladder disease and form as a result of too much cholesterol or bilirubin (a pigment that is made in the liver when red blood cells are broken down).

Gallstones are crystals that form inside the gallbladder, which is a pear-shaped organ located in the upper right side of your abdomen under your liver.

What Does the Gallbladder Do?

Your gallbladder stores bile—a fluid made by the liver that's necessary for digesting and absorbing fat and vitamins.

With cholesterol gallstones, your bile is "overwhelmed" with cholesterol and not able to dissolve it like it normally does, so stones form. The vast majority of people with gallstones in the United States have cholesterol stones.

Pigment gallstones may form if there is too much bilirubin. Medical conditions like cirrhosis (too much bilirubin is made by the liver) and sickle cell disease (where red blood cells are broken down) may cause pigment stones.

Lastly, gallstones may form if the gallbladder does not empty bile properly (this is called bile stasis).

Some of the risk factors for developing gallstones include:

  • Female gender
  • Age older than 40
  • Pregnancy
  • Obesity
  • Diets high in cholesterol, refined carbohydrates (for example, white bread), and saturated fats (for example cheese, butter, and red meat)
  • Sedentary lifestyle
  • Rapid weight loss
  • Underlying diseases (for example, diabetes, metabolic syndrome, cirrhosis, Crohn's disease, cystic fibrosis, sickle cell disease, or a spinal cord injury)
  • Medications that contain estrogen, like oral contraceptives or hormone replacement therapy
  • Other medications such as Sandostatin (octreotide), Rocephin (ceftriaxone), and thiazide diuretics like Microzide (hydrochlorothiazide)

Gallbladder Disease Doctor Discussion Guide

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Rarer Causes

There are a number of other less frequent causes of gallbladder disease.


Inflammation of the gallbladder (called cholecystitis) may develop as a result of gallstones (called acute cholecystitis) or less commonly, without gallstones (called acalculous cholecystitis).

Acute cholecystitis occurs when a gallstone becomes lodged within the cystic duct, leading to gallbladder inflammation. In addition to the typical pain (biliary colic) of having a gallstone, a person may have a fever, nausea, vomiting, malaise, and/or a loss of appetite. An elevated white blood cell count is also usually present.

Acalculous cholecystitis causes the same symptoms and signs as acute cholecystitis, however, there is no gallstone present. Instead, experts believe this condition results from gallbladder stasis and ischemia (poor blood flow).

Acalculous cholecystitis typically occurs in people who are severely ill.

Some factors that increase a person's chance of developing acalculous gallbladder disease include:

  • Serious illnesses (for example, acute myelogenous leukemia, AIDs, coronary heart disease, heart failure diabetes, end-stage kidney disease, and vasculitis)
  • Burns
  • Childbirth
  • Suppressed immune system
  • Major infection or trauma
  • Certain medications (for example, opiates)
  • Multiple transfusions
  • Mechanical ventilation
  • Receiving nutrition through your vein (called total parenteral nutrition)

Biliary Dyskinesia

Biliary dyskinesia describes a syndrome of biliary duct system obstruction related to a functional abnormality of the sphincter of Oddi.

The muscular structure surrounds the area where the common bile duct joins up with the pancreatic duct as they enter the small intestine. Since the sphincter of Oddi does not function properly in this disease, a biliary obstruction may occur.

Intermittent episodes of biliary obstruction cause dull pain in the upper right or upper center part of the abdomen.

While an abdominal ultrasound may reveal a widened common bile duct, a test called the sphincter of Oddi manometry can be used to definitively diagnose biliary dyskinesia. If the sphincter of Oddi pressure is elevated (the test is positive), a person may undergo removal of the sphincter (called an endoscopic sphincterotomy).

It's unclear what causes biliary dyskinesia. It's seen most often in people who have had their gallbladders removed; although the vast majority of people who have had their gallbladders removed do not experience biliary dyskinesia.

Other experts have suggested that this disorder results from spasm or nerve loss to the sphincter muscle.

Functional Gallbladder Disorder

Functional gallbladder disorder refers to people who experience biliary pain (discomfort in the upper right or center part of the abdomen) in the absence of gallstones or a sphincter of Oddi dysfunction.

People with functional gallbladder disorder have normal blood tests, without evidence of inflammation or liver problems. They also have a normal ultrasound of the gallbladder with no evidence of gallstones.

After ruling out other conditions that may mimic biliary pain (for example, ischemic heart disease or peptic ulcer disease), a person may undergo a test called cholecystokinin (CCK)-stimulated cholescintigraphy to confirm the diagnosis of a functional gallbladder disorder.

This test calculates the ejection fraction of the gallbladder (how much tracer leaves the gallbladder). If the ejection fraction is low, like less than 40 percent, the test supports a diagnosis of a functional gallbladder disorder. Treatment of this disorder entails removal of the gallbladder (called a cholecystectomy).

While still unclear, it's possible that people with an underlying gastrointestinal motility issue (for example, abnormal gastric emptying) may be at risk for developing functional gallbladder disorder.

Gallbladder Cancer

Gallbladder cancer is rare and occurs when cells in the gallbladder grow rapidly and uncontrollably.

Both gallstones and primary sclerosis cholangitis increase a person's chance of developing gallbladder cancer, although gallstones are far more common. 

According to the American Cancer Society, at least four out of five people with gallbladder cancer have gallstones when they are diagnosed. However, the vast majority of people with gallstones do not have and will never develop gallbladder cancer.

Other risk factors for developing gallbladder disease include:

  • Female gender
  • Older age
  • Obesity
  • Ethnicity (Mexican American or Native American)
  • Chronic infection with the bacteria, Salmonella Typhi
  • Cysts within the common bile duct
  • Gallbladder polyps
  • Abnormalities of the bile ducts
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