What Causes Gallstones (Cholelithiasis)?

Gallstones (also known as cholelithiasis) are hard, pebble-like deposits that can form in your gallbladder, a pear-shaped digestive organ beneath the liver. These deposits consist of minerals like cholesterol and bilirubin that collect in your bile—a digestive fluid produced in the liver and stored in the gallbladder.

Research estimates that up to 15% of Americans will develop gallstones at some point in their life, but people assigned female at birth have a slightly higher risk. Gallstones can vary widely in size—some are as small as a grain of rice, while others are the size of a golf ball. Most gallstones don't cause symptoms, but symptoms may develop if you have a large gallstone or if your gallstones get stuck in your bile ducts.

You can develop gallstones for several reasons. They can often result from internal imbalances, such as too much cholesterol, bilirubin (a byproduct of red blood cell breakdown), or bile within the gallbladder. However, various health conditions and lifestyle habits can also raise your risk of forming gallstones.

Too Much Cholesterol

Bile is a yellow-green fluid that your liver produces and your gallbladder stores. Bile carries waste and excess cholesterol from the liver to the gallbladder and releases it into the small intestine. This process aids digestion, helping your body absorb vitamins and digest fats.

Normally, salts in the bile can break down cholesterol that gets excreted (or, discharged) from the liver. When there's too much cholesterol, the buildup can harden and form crystals. Over time, these crystals can turn into stones, which can sometimes get stuck in the bile ducts, causing symptoms to occur. Cholesterol gallstones are the most common type, making up about 80-90% of all gallstone cases.

Bilirubin Build-Up

Your body regularly “recycles” blood cells, breaking down old cells and making new ones. Bilirubin is a yellow pigment left over from the breakdown of old red blood cells (RBCs). Like cholesterol, bilirubin is a substance that moves from the liver to the gallbladder through bile.

However, certain health conditions can cause your liver to make too much bilirubin, which can cause your gallbladder to form pigment stones. These types of stones are darker in color, usually appearing brown or red. Pigment stones are more rare, causing only 3% of all gallstone cases. You may have a higher risk of developing pigment stones if you have an underlying blood disorder, such as anemia.

Excess Bile

If the gallbladder can’t empty itself like it should, bile can build up inside. The high concentration of bile can cause crystal deposits and influence the formation of gallstones. Too much bile in your system can cause both cholesterol and pigment stone types.

Generally, dysfunction within the gallbladder and other underlying health concerns can cause an excess of bile. These include injuries, infections, nerve disorders, and intestinal diseases.

Are Gallstones Hereditary? 

Evidence suggests genetics can play a significant role in the development of gallstones. Researchers have identified 20 genes associated with gallstones, including ABCG5/ABCG8 and CYP7A1. Many of these genes can be passed down from parent to child, which is why having a family history of gallstones is a risk factor for the condition.

Certain genes that are passed down affect the function of your liver and pancreas, raising the risk of gallbladder-related problems and blockages. Researchers have noted that about 36% of all gallstone cases run in families. Among this population, 50.9% had parents and 35.1% had siblings with a history of gallstones.

Risk Factors 

Several underlying health conditions and lifestyle factors can increase your risk of developing gallstones. These factors often affect your gallbladder’s ability to break down bilirubin, cholesterol, or both, which can lead to the formation of stones.

Hormonal Fluctuation

In people assigned female at birth, high levels of the hormone estrogen can raise gallstone risk. As such, pregnancy, hormone replacement therapy (medications that use estrogen or estrogen derivatives), and certain types of birth control are all risk factors for gallstones.

Obesity

Obesity can significantly affect your liver and gallbladder function. When the functionality of your liver and gallbladder becomes impaired, it's harder for your body to process bile properly, which can increase the risk of a gallstone forming.

Rapid Weight Loss

On the other hand, rapidly losing weight can also raise your risk. Bariatric (weight loss) surgeries like gastric bypass, in particular, can affect the function of your organs too quickly. Researchers found between 10-38% of people who undergo weight loss surgery eventually develop gallstones.

Liver and Bile Duct Infections

Severe liver scarring (medically known as cirrhosis) can often occur due to hepatitis infections and excessive alcohol use. When your liver and its tissues become scarred, it can affect how well your liver can function and cause a chemical imbalance in your bile.

Similarly, infection in your bile ducts (medically known as cholangitis) can also affect your bile. Your bile ducts are tubes that transport bile in and out of the liver. When these ducts become infected or inflamed, you may have a higher risk of developing gallstones.

Anemia

Anemia is a group of blood disorders that causes red blood cells to break down prematurely. Sickle cell anemia (an inherited form of anemia that causes the red blood cells to be irregularly shaped) is often associated with gallstones. In one study of people who live with sickle cell anemia, about 25.2% of all participants developed gallstones.

Diabetes Mellitus

Diabetes mellitus makes it difficult for your body to break down and digest glucose (sugar)—which can raise your blood sugar levels. The condition occurs either when the pancreas doesn’t make enough insulin or when your body doesn’t use insulin properly. Researchers found that having diabetes can raise your chances of developing gallstones by 46%.

Cholesterol Issues

As gallstones often occur from excess cholesterol, high cholesterol levels in your blood can also increase the risk of gallstones. There are two main cholesterol types: high-density lipoprotein (HDL) and low-density lipoprotein (LDL). HDL is often known as "good" cholesterol and LDL is called "bad" cholesterol. Too much LDL in your blood can increase the likelihood of getting gallstones.

Metabolic Syndrome

Metabolic syndrome is a term for a combination of several health concerns, which can occur when you have three of the following:

• Hyperglycemia (elevated blood sugar levels)
• Hypertension (high blood pressure)
• Obesity
• Raised triglyceride levels (a type of fat)
• Low HDL cholesterol

In a wide-ranging study of 12,050 people with metabolic syndrome, researchers found that people with this condition were 1.75 times as likely to develop gallstones than people without metabolic syndrome.

Intestinal Diseases

Your intestines help absorb nutrients and vitamins from the foods you eat. Certain inflammatory bowel conditions, such as Crohn’s disease, can affect this function and your overall digestion. Because bile is an important substance in digestion, any impairment in how your body processes food can alter the chemical balance of your gallbladder, raising the risk of gallstones.

Lifestyle Habits

Alongside underlying health conditions, your lifestyle habits can also influence your likelihood of developing gallstones. These include:

• Eating a diet high in carbohydrates and sugar
• Consuming too little fiber
• Not getting enough physical activity every day
  

A Quick Review 

Gallstones are small, pebble-like deposits that form in the gallbladder, a small organ below your liver. While gallstones are often asymptomatic, they can cause symptoms if the stones get stuck in your bile ducts.

Chemical imbalances in your bile are the main reason why gallstones develop. Underlying health conditions like liver and bile duct infections, obesity, and hormonal changes can all increase your risk of getting gallstones.