The gallbladder is a small, pear-shaped organ located beneath the liver. It plays a crucial role in digestion by storing and releasing bile, a digestive fluid produced by the liver. Bile is essential for breaking down and absorbing dietary fats, fat-soluble vitamins, and cholesterol in the small intestine. Gallstones can form when the soluble components of bile become supersaturated and crystallize. Up to 25 million Americans are affected by gallstones. (19)

While many gallstones may be asymptomatic and benign, stones can increase the risk of gallbladder inflammation, blockages within the bile and pancreatic ducts, and gallbladder cancer (9). Using labs to understand the reason behind the presence of gallstones can prevent their formation, associated health complications, and the need for cholecystectomy (surgical removal of the gallbladder).  

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What Are Gallstones?

Gallstones, or cholelithiasis, are small, solid particles that form in the gallbladder. The gallbladder stores bile, a digestive fluid produced by the liver, and releases it into the small intestine to aid in the digestion of fats.

There are two main types of gallstones. Cholesterol gallstones are the most common type, accounting for 80% of stones, and are primarily composed of cholesterol. They form when there's excessive cholesterol secretion into the bile, leading to cholesterol crystallization into solid particles. Cholesterol stones are usually yellow-green. Pigment gallstones are made of bilirubin, a waste product derived by the breakdown of red blood cells that is processed and secreted into bile by liver cells. When there's an excess of bilirubin or the liver fails to process it properly, it can combine with other substances in the bile to form solid pigment stones. These stones are usually smaller and darker in color than cholesterol gallstones. (12, 18) 

Gallstones can vary in size, from tiny specks to larger stones that can be several centimeters in diameter (comparable to the size of a golf ball). They may not cause any symptoms in some people and may only be detected incidentally during medical imaging for other reasons. (19) 

Treatment for gallstones depends on the severity of symptoms and the risk of complications. In cases where gallstones are causing significant discomfort or complications, such as blocking the bile ducts, surgical removal of the gallbladder (cholecystectomy) is often recommended. In less severe cases, dietary changes, medications, and other non-surgical approaches may be considered to manage symptoms and prevent further stone formation. (19) 

What Causes Gallstones?  

Various factors will contribute to the development of gallstones. Gallstones generally develop due to lithogenic bile, biliary stasis, and intestinal dysbiosis. Lithogenic bile has an increased tendency to promote the formation of gallstones because the various components of bile become imbalanced, promoting the aggregation and crystallization of cholesterol or bilirubin.

Healthy gallbladder motility plays a necessary role in gallstone prevention. If the gallbladder does not contract effectively to release bile into the digestive system, called biliary dyskinesia, bile can become concentrated to form biliary sludge, which promotes gallstone formation.

Emerging research suggests that dysbiosis in the gut microbiota may also play a role in gallstone formation. The gut microbiota influences cholesterol metabolism and the enterohepatic circulation of bile acids. Dysbiotic patterns, including an overabundance of Clostridium, Bifidobacterium, Peptostreptococcus, Bacteroides, Eubacterium, and Escherichia coli, can disrupt enterohepatic circulation and induce liver inflammation. In addition to affecting bile metabolism, the microbiota can also contribute to gallstone disease by causing intestinal permeability and systemic inflammation. H. pylori infection also contributes to the formation of gallstones and increases the risk of gallstone-induced cholecystitis. (10) 

Numerous factors have been identified as contributing to gallbladder dysmotility, bile supersaturation, and the risk of gallstone formation. Both obesity and rapid weight loss can lead to excess cholesterol secretion into bile. Estrogen can increase bile saturation with cholesterol; estrogen-dominant states, such as pregnancy and using estrogen-containing drugs, will increase gallstone risk. Medical conditions, including diabetes, metabolic syndrome, sickle cell anemia (SCA), and inflammatory bowel disease (IBD), also increase the likelihood of gallstone formation (19). (9) 

Gallstone Symptoms

More than 80% of patients with gallstones are asymptomatic. However, approximately 20% of asymptomatic gallstones will develop symptoms over 15 years. Symptoms often occur when large gallstones become lodged in the bile duct system and cause a blockage. Gallstones may also cause cholecystitis, inflammation of the gallbladder, over time, perpetuating abdominal symptoms. (16) 

Symptoms associated with cholelithiasis and cholecystitis include (15, 19): 

• Right upper abdominal pain that is sharp and cramp-like and radiates between the shoulder blades and into the right shoulder, especially after consuming fatty foods
• Nausea and vomiting
• Yellowing of the skin and eyes (jaundice)
• Fever 

What Are the Benefits of Regular Lab Testing for Patients With Gallstones?

Regular lab testing provides healthcare professionals with important information to make informed decisions about patient care. Lab testing plays a crucial role in assessing the patient's condition by providing valuable insights into the patient's overall health and helping to monitor any potential complications related to gallstone formation. Functional medicine tests measure non-standard biomarkers to help uncover underlying gut and metabolic health disruptions that can negatively influence liver and gallbladder function. By identifying and correcting imbalances, the long-term treatment and prevention of gallstones become more successful, reducing the rate of gallstone-associated complications and the need for surgical intervention.

Top Labs to Run Bi-Annually on Patients With Gallstones

The following labs are recommended to monitor liver and gallbladder health, screen for infection and inflammation caused by gallstones, and identify the root causes of gallstone formation. 

Complete Blood Count (CBC)

A CBC identifies and counts the types of cells in the blood, including red and white blood cells. This test can indicate the presence of hemolytic anemia (increased red blood cell destruction), a cause of elevated bilirubin, and infection, which is a risk in the presence of bile duct obstruction.

Comprehensive Metabolic Panel (CMP)

Using a CMP to measure ALT, AST, alkaline phosphatase, and bilirubin helps monitor liver and gallbladder function. Elevations in these markers can indicate the presence of inflammation or obstruction in the hepatobiliary system. 

Comprehensive Stool Analysis

A comprehensive stool analysis is one of the best diagnostic tools for intestinal dysbiosis. This test qualifies and quantifies the species of bacteria in the stool and can also detect pathogenic microorganisms, such as H. pylori, that can contribute to inflammation in the intestines, liver, and gallbladder. Additionally, intestinal markers of inflammation and permeability are included or can be added to these panels. Examples include calprotectin, which can indicate the presence of active IBD when elevated, and zonulin, a marker of impaired intestinal barrier function ("leaky gut").

Cardiometabolic Assessment

Regular lab testing should include monitoring serum glucose and cholesterol levels. A diabetes panel and comprehensive lipid panel assess the risk of developing diabetes, metabolic syndrome, and high cholesterol, all of which can influence gallstone formation. 

Thyroid disorders, both hypo- and hyperthyroidism, promote gallstone formation and can be screened for with a thyroid panel. The thyroid gland produces hormones essential for regulating metabolism. Dysfunction of this gland will have negative downstream effects in nearly every body system, including the digestive tract. Over- and underproduction of thyroid hormones influence cholesterol metabolism and can induce cholesterol gallstone formation. (17)  

C-Reactive Protein (CRP)

CRP levels indicate the presence and quantify the amount of inflammation in the body, which might occur due to gallstone complications like cholecystitis or infection.

Other Labs to Check

Abdominal ultrasound is the imaging modality of choice to evaluate for the presence of and monitor gallstones. Patients with suspected cholelithiasis, based on clinical symptoms, should be referred for an ultrasound. Sometimes, a hepatobiliary iminodiacetic acid (HIDA) scan may be ordered to rule out biliary dyskinesia. (1) 

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Summary

In conclusion, regular lab testing is pivotal in ensuring the holistic health and well-being of patients with gallstones. By identifying changes in bile composition, assessing liver function, monitoring inflammation, and evaluating potential complications, healthcare professionals can proactively manage gallstone-related risks and tailor interventions to each patient's needs.