Gallbladder stones (cholelithiasis) refer to the presence of stones in the gallbladder and are a common condition. Cholecystitis, a common complication of gallbladder stones, can also occur in the absence of stones.
Risk Factors and Mechanism of Stone Formation
Risk Factors
Risk factors include age over 40, female, pregnancy, oral contraceptive use, hormone replacement therapy, certain lipid-lowering drugs, parenteral nutrition, obesity, rapid weight loss, diabetes, liver cirrhosis, and reduced gallbladder motility. Statins, vitamin C, coffee, plant proteins, nuts, polyunsaturated fats, and monounsaturated fats may have a protective effect against gallbladder stones.
Mechanism of Stone Formation
The stability of bile is maintained by cholesterol, lecithin, and bile salts. When cholesterol becomes supersaturated, it tends to precipitate into crystals, leading to stone formation. During the process of gallstone formation, mucin glycoproteins, mucopolysaccharides, macromolecular proteins, immunoglobulins, divalent metal cations (such as calcium and magnesium), and oxygen free radicals play significant roles. Additionally, reduced gallbladder contractility and bile stasis within the gallbladder further promote stone formation.
Pathology
In acute cholecystitis, the gallbladder wall exhibits edema and acute inflammation. In severe cases, necrosis and gangrene of the gallbladder wall may occur, and the gallbladder fluid may appear purulent, bloody, or dark brown. Prolonged impaction of stones in the cystic duct can lead to gallbladder distension, with the gallbladder filled with thick, white, mucus-like bile.
Pathological changes in acalculous cholecystitis include ischemia, distension, endothelial damage, and necrosis of the gallbladder.
Clinical Manifestations
Gallbladder stones are primarily observed in adults and can be categorized into three types: (1) asymptomatic, (2) symptomatic, and (3) with complications. The natural course of the disease generally progresses in this order.
Asymptomatic Gallbladder Stones
These stones do not cause clinical symptoms and are often discovered incidentally during abdominal imaging or surgery performed for other reasons.
Symptomatic Gallbladder Stones
The presentation of symptoms depends on the size and location of the stones, as well as the presence of infection, obstruction, and gallbladder function.
Gastrointestinal Symptoms of Dyspepsia
Most patients experience vague discomfort or dull pain in the upper abdomen or right upper quadrant, often after eating, particularly fatty meals. Symptoms may include bloating, belching, and hiccups, which are often misdiagnosed as "stomach problems."
Biliary Colic
Biliary colic is a classic symptom of gallbladder stones. The pain is typically located in the upper abdomen or right upper quadrant, presenting as intermittent or sustained pain that intensifies in episodes. Pain may radiate to the scapular region or back and is often accompanied by nausea and emesis. It frequently occurs after a heavy or fatty meal, resulting from gallbladder contraction, stone displacement, impaction at the gallbladder neck or infundibulum, impaired bile drainage, increased intragallbladder pressure, and intense contraction of the gallbladder smooth muscle, leading to colicky pain.
Complications of Gallbladder Stones
Acute Cholecystitis
In the first 24 hours of an acute cholecystitis episode, chemical inflammation is predominant, while bacterial infection gradually becomes more significant after 24 hours. Pathogens often ascend from the biliary tract into the gallbladder or reach the gallbladder through hematogenous or lymphatic pathways. When bile outflow is obstructed, infection may occur, potentially progressing to suppurative cholecystitis in severe cases. The most common pathogens are Gram-negative bacilli, especially Escherichia coli and Klebsiella pneumoniae. Persistent obstruction of the cystic duct can lead to increased intragallbladder pressure, compression of the blood vessels in the gallbladder wall, and subsequent ischemia and necrosis, resulting in gangrenous cholecystitis. Gangrenous cholecystitis is often complicated by gallbladder perforation, which typically occurs at the fundus or neck of the gallbladder.
Clinical manifestations include persistent right upper quadrant pain that may radiate to the right shoulder or back. Fever is common, often with a temperature below 38.5°C, and may be accompanied by upper abdominal or right upper quadrant muscle tension, a positive Murphy's sign, or a palpable mass in the right upper quadrant. Symptoms of untreated acute cholecystitis may resolve within approximately one week. However, complications such as gallbladder necrosis, perforation, cholecystoenteric fistula, gallstone ileus, and emphysematous cholecystitis can be life-threatening.
Gallbladder Hydrops
Prolonged impaction or obstruction of the cystic duct by gallbladder stones without associated infection may result in the absorption of bile pigments by the gallbladder mucosa and the secretion of mucus, leading to the accumulation of a clear, colorless fluid in the gallbladder.
Secondary Common Bile Duct Stones and Biliary Pancreatitis
These conditions are discussed in related sections.
Mirizzi Syndrome
Large stones persistently impacted in the gallbladder neck or cystic duct can compress the common hepatic duct or cause recurrent inflammation, leading to common hepatic duct stricture or cholecystocholedochal fistula. Stones may partially or completely obstruct the common hepatic duct, resulting in recurrent episodes of cholecystitis, cholangitis, and obstructive jaundice. The anatomical basis for this condition includes a long parallel course of the cystic duct and common hepatic duct or a low junction between the cystic duct and common hepatic duct.
Cholecystoenteric or Cholecystocolonic Fistula and Gallstone Ileus
Chronic inflammation and perforation caused by gallstone compression may result in a cholecystoduodenal or cholecystocolonic fistula. Large stones can pass through the fistula into the intestinal tract and obstruct the terminal ileum, leading to intestinal obstruction.
Chronic Cholecystitis
More than 90% of patients with chronic cholecystitis have gallbladder stones. Recurrent inflammation can cause adhesions between the gallbladder and surrounding tissues, thickening and scarring of the gallbladder wall, gallbladder atrophy, and loss of function. During acute exacerbations of chronic cholecystitis, the gallbladder is generally not palpable.
Gallbladder Cancer
Prolonged irritation from stones and inflammation may promote the development of gallbladder cancer. Patients with a gallstone history exceeding 10 years or stones larger than 3 cm are at an increased risk of malignancy.
Acute Acalculous Cholecystitis
Acute acalculous cholecystitis is an acute inflammatory and necrotic condition of the gallbladder, accounting for approximately 10% of acute cholecystitis cases. It is more commonly observed in hospitalized and critically ill patients and is associated with a high rate of complications and mortality. Clinical manifestations are often insidious and may include unexplained fever, leukocytosis, or vague abdominal discomfort. Jaundice or a right upper quadrant mass may also occur. By the time a definitive diagnosis is made, complications such as gallbladder necrosis, gangrene, and perforation are often present, along with sepsis, shock, or peritonitis.
Laboratory and Other Examinations
Abdominal ultrasound is the preferred diagnostic method for gallbladder stones. Stones appear as hyperechoic structures with posterior acoustic shadowing and may shift with changes in body position. CT, MRI, and MRCP can also detect gallbladder stones.
Patients with acute cholecystitis often exhibit leukocytosis with a predominance of neutrophils. Abdominal ultrasound may reveal gallbladder stones, wall thickening, or edema. In chronic cholecystitis, ultrasound findings may include gallbladder atrophy and wall thickening.
Diagnosis and Differential Diagnosis
Uncomplicated Gallbladder Stones
The diagnosis is confirmed through imaging studies such as abdominal ultrasound, which identifies gallbladder stones. Symptomatic cases require differentiation from conditions such as peptic ulcers, gastritis, gastric tumors, functional dyspepsia, pancreatic diseases, functional gallbladder disorders, sphincter of Oddi dysfunction, right-sided ureteral stones, and acute coronary syndrome.
Acute Cholecystitis
Acute cholecystitis should be suspected in patients with right upper quadrant or upper abdominal pain, fever, leukocytosis, a positive Murphy's sign, or a palpable right upper quadrant mass. Confirmation can be achieved through imaging studies such as abdominal ultrasound, which may demonstrate gallbladder enlargement, wall edema, or obstruction caused by gallstones.
Differential diagnosis includes acute pancreatitis, appendicitis, peptic ulcers, acute gastroenteritis, functional gallbladder disorders, sphincter of Oddi dysfunction, acute small or large intestinal diseases, right kidney and ureteral diseases, right lung and pleural inflammation, and acute coronary syndrome.
Treatment
Currently, there is no evidence to suggest that medications or other non-surgical therapies can completely dissolve or eliminate gallstones. The primary treatment for gallbladder stones is surgical removal of the gallbladder. Minimally invasive procedures aimed at removing stones while preserving the gallbladder are still under investigation.
Uncomplicated Gallbladder Stones
Observation is generally adopted, with treatment measures implemented when symptoms occur. However, surgical treatment should be considered even in asymptomatic cases under the following circumstances:
- Thickened or calcified gallbladder wall, or porcelain gallbladder;
- Gallbladder atrophy or progressively enlarging gallbladder polyps;
- Stones with a diameter >3 cm;
- Gallbladder stones present for more than 10 years;
- Elderly patients with diabetes or cardiopulmonary diseases;
- During other elective upper abdominal surgeries;
- Gallbladder stones in children.
Acute Cholecystitis
General treatment includes fasting, and for patients with emesis or abdominal distension, nasogastric decompression may be performed. Intravenous fluid replacement, correction of electrolyte imbalances, and pain management are also part of the treatment. Empirical antibiotic therapy may be initiated when the causative pathogen is not identified early, with cephalosporins or carbapenems being commonly used. For recurrent acute cholecystitis associated with gallstones, cholecystectomy should be considered.
For patients with acute acalculous cholecystitis, antibiotic therapy is recommended based on blood culture and drug sensitivity test results. Depending on the progression of the disease, cholecystectomy or cholecystostomy may be performed.
Cholecystectomy is suitable for elective surgeries or patients with mild inflammation during acute episodes. Laparoscopic cholecystectomy (LC) is the preferred surgical approach due to its advantages, including minimal trauma, reduced pain, faster postoperative recovery, shorter hospital stays, and smaller scars.
In cases where laparoscopic facilities are unavailable, open cholecystectomy may be performed. Percutaneous transhepatic gallbladder drainage can be used to reduce intragallbladder pressure in critically ill patients with suppurative cholecystitis who are unfit for surgery. Elective surgery can then be considered after the acute phase has resolved.