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Why one organ causes so many different diseases

The gallbladder is a small, pear-shaped pouch tucked under the liver. Its only job is to store and concentrate bile — the digestive fluid the liver makes — and to squeeze it into the intestine when you eat a fatty meal (Baiu & Hawn, JAMA, 2018). It sounds simple. Yet diseases of the gallbladder and bile ducts are among the most common reasons for abdominal surgery in the world, and together they represent a major and growing global health burden (Dai et al., BMC Gastroenterology, 2025).

The reason a single organ produces so many different diagnoses comes down to one thing: where a gallstone goes. A stone that sits quietly in the gallbladder causes nothing at all. A stone that briefly blocks the gallbladder's outlet causes an attack of pain. A stone that lodges permanently causes infection. And a stone that escapes into the main bile duct can block the liver's drainage, inflame the pancreas, or trigger a life-threatening infection (Baiu & Hawn, JAMA, 2018; Patel & Jepsen, American Family Physician, 2024). Understanding this one idea — that the destination of the stone determines the disease — makes the entire spectrum easy to follow.

It starts with gallstones (cholelithiasis)

Gallstones are crystalline deposits that form in the gallbladder from bile pigments, cholesterol, or calcium salts (Dai et al., BMC Gastroenterology, 2025). They are remarkably common: in the United States, 10% to 15% of adults have gallstones, and cholesterol stones are the most frequent type (Patel & Jepsen, American Family Physician, 2024).

Several factors raise the risk of forming them, including female sex, older age, certain medications, type 2 diabetes, non-alcoholic fatty liver disease, obesity, rapid weight loss, and hemolytic anemia (Patel & Jepsen, American Family Physician, 2024).

Here is the most reassuring fact in all of biliary medicine: nearly 80% of gallstones are found by accident and never cause a single symptom (Patel & Jepsen, American Family Physician, 2024). Silent, asymptomatic gallstones generally do not need treatment — they simply need to be left alone and watched (Patel & Jepsen, American Family Physician, 2024). Surgery enters the picture only when stones begin to cause symptoms or complications. Across a person's lifetime, only about one in five people with gallstone disease will ever develop a complication, and those complications are caused by stones migrating out of the gallbladder into the cystic or common bile duct (Patel & Jepsen, American Family Physician, 2024).

The first symptom: biliary colic

When a gallstone temporarily blocks the gallbladder's drainage channel (the cystic duct), the gallbladder contracts hard against the blockage and produces the signature symptom of gallstone disease — biliary colic (Baiu & Hawn, JAMA, 2018). Despite the name, the pain is not actually "colicky" or cramping; it is an intense, steady pain in the upper-right or upper-middle abdomen that often radiates to the back or right shoulder blade, frequently begins an hour or two after a fatty meal, and typically eases within a few hours once the stone falls back into the gallbladder (Gallaher & Charles, JAMA, 2022; Patel & Jepsen, American Family Physician, 2024).

Biliary colic is the most common way gallstone disease announces itself, with an annual incidence between 1% and 4% (Lin et al., Surgical Endoscopy, 2020). It is a warning sign, not an emergency — but it signals that the stones are now active, and that further attacks or complications may follow (Baiu & Hawn, JAMA, 2018).

When a stone gets stuck: acute cholecystitis

If a stone does not fall back but instead remains lodged in the cystic duct, bile backs up, the gallbladder wall becomes inflamed and infected, and the result is acute cholecystitis — the single most common complication of gallstones (Patel & Jepsen, American Family Physician, 2024). Unlike biliary colic, the pain of cholecystitis persists beyond six hours, and it is often accompanied by fever, nausea, and vomiting (Patel & Jepsen, American Family Physician, 2024).

A classic examination finding is the Murphy sign — a catch in the breath when the examiner presses under the right rib cage — which is one of the most specific bedside clues to the diagnosis (Patel & Jepsen, American Family Physician, 2024). Acute cholecystitis is a surgical problem: it requires prompt evaluation and, in most cases, gallbladder removal (Gallaher & Charles, JAMA, 2022).

When a stone escapes: bile duct stones (choledocholithiasis)

Sometimes a stone passes out of the gallbladder and into the common bile duct — the main pipe that drains bile from the liver into the intestine. This is called choledocholithiasis, and it occurs in roughly 10% to 20% of people with symptomatic gallstones (Patel & Jepsen, American Family Physician, 2024). A stone in the common bile duct is more dangerous than one in the gallbladder, because it can block the drainage of the entire liver and set off two serious downstream complications (Patel & Jepsen, American Family Physician, 2024). Patients with bile duct stones often show elevated bilirubin and liver enzymes on blood tests, and MRCP — a specialized, non-invasive MRI of the bile ducts — is the most accurate way to confirm them (Patel & Jepsen, American Family Physician, 2024).

The two emergencies: gallstone pancreatitis and cholangitis

A stone that travels all the way down and obstructs the sphincter of Oddi — the shared drainage valve where the bile duct and pancreatic duct meet — can back up the pancreas and cause gallstone pancreatitis, a painful and potentially severe inflammation of the pancreas (Patel & Jepsen, American Family Physician, 2024).

The other emergency is ascending cholangitis — infection of the bile ducts themselves. When a stone blocks bile flow, bacteria from the intestine invade the stagnant bile and the infection spreads rapidly upward toward the liver (Patel & Jepsen, American Family Physician, 2024). Cholangitis classically presents with the triad of fever, jaundice (yellowing of the skin and eyes), and right-upper-quadrant pain, and it can cause critical illness very quickly (Patel & Jepsen, American Family Physician, 2024; Gallaher & Charles, JAMA, 2022). Both of these conditions are medical emergencies that require urgent care.

The "stone-free" problem: functional gallbladder disorders

Not all gallbladder pain comes from stones. Some patients have classic biliary pain, yet their ultrasound shows a completely normal, stone-free gallbladder. This is a functional gallbladder disorder — historically called biliary dyskinesia — in which the gallbladder causes pain because of the way it works rather than because of a visible blockage (Richmond, JAMA Surgery, 2024). The diagnosis rests on typical biliary pain plus a normal ultrasound, and it is often supported by a reduced gallbladder ejection fraction on a CCK-HIDA scan, a test that measures how well the gallbladder squeezes (Richmond, JAMA Surgery, 2024).

This is one of the more nuanced and debated areas of biliary medicine. Importantly, a functional gallbladder disorder does not cause the dangerous complications of stones, and symptoms resolve on their own in up to half of patients — which is why a period of watchful waiting is wise before considering surgery (Elmunzer et al., Gastroenterology, 2026). The newest Rome consensus even de-emphasizes the HIDA ejection fraction, noting that the presence of genuinely typical biliary pain is a far better predictor of who will benefit from gallbladder removal (Elmunzer et al., Gastroenterology, 2026). In other words, success here depends almost entirely on careful patient selection.

How these diseases are diagnosed

The workup is logical and follows the stone (Patel & Jepsen, American Family Physician, 2024):

• Ultrasound is the first and best test to detect gallstones and acute cholecystitis.

• A HIDA scan is used when the ultrasound is normal or unclear — either to confirm cholecystitis or to measure gallbladder function in suspected functional disorders.

• MRCP (MRI of the bile ducts) is the accurate, non-invasive test for finding stones in the common bile duct.

• Blood tests — liver enzymes, bilirubin, and pancreatic enzymes (amylase and lipase) — help reveal whether a stone has moved into the bile duct or is irritating the pancreas.

How these diseases are treated

For the great majority of patients with symptomatic gallstones — whether biliary colic or acute cholecystitis — the definitive treatment is laparoscopic cholecystectomy, the minimally invasive removal of the gallbladder, and it is the treatment of choice (Patel & Jepsen, American Family Physician, 2024). It is one of the most common and safest operations in surgery, and because the liver keeps making all the bile the body needs, patients live completely normal lives afterward (Baiu & Hawn, JAMA, 2018). Non-steroidal anti-inflammatory drugs (NSAIDs) are safe and effective for controlling the pain of biliary colic and cholecystitis in the meantime (Patel & Jepsen, American Family Physician, 2024). Medications to dissolve stones (ursodeoxycholic acid and chenodeoxycholic acid) are not used routinely and are reserved for select patients who are poor surgical candidates (Patel & Jepsen, American Family Physician, 2024).

When stones have escaped into the common bile duct, they must be cleared in addition to removing the gallbladder. This is usually done either as a two-stage approach — an endoscopic procedure called ERCP (endoscopic retrograde cholangiopancreatography) to extract the duct stone, followed by laparoscopic gallbladder removal — or as a single-stage approach combining gallbladder removal with laparoscopic common bile duct exploration (LCBDE) during the same operation (Delcarro et al., Surgical Endoscopy, 2026; Vaccari et al., Digestive Diseases and Sciences, 2022). Both strategies achieve comparable stone clearance and safety; the single-stage approach can mean one procedure, one anesthetic, and a shorter hospital stay, while preserving the function of the sphincter of Oddi (Zhu et al., Surgical Endoscopy, 2021). The right choice depends on the clinical situation and on local surgical and endoscopic expertise (Vaccari et al., Digestive Diseases and Sciences, 2022).

The bottom line for patients

Gallbladder and bile duct disease is best understood as a single spectrum rather than a list of unrelated diagnoses. It usually begins with gallstones, most of which stay silent. When stones become active, they announce themselves with biliary colic. From there, the destination of the stone determines everything — a stuck stone causes cholecystitis, an escaped stone causes bile duct obstruction, and a stone at the final valve can trigger pancreatitis or cholangitis. A separate group of patients has biliary pain with no stones at all. The unifying good news is that nearly all of these conditions are treatable — and in most cases curable — with modern minimally invasive surgery and endoscopy. The key is recognizing the symptoms, getting the right test, and being evaluated by an experienced surgeon before a simple problem becomes an emergency.

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