Gallstones or cholelithiasis are responsible for one of the most prevalent digestive disorders in the United States. They are considered a disease of developed populations but are present around the world. It is both the result of a chronic disease process and the cause of subsequent acute disorders of the pancreatic, biliary, hepatic and gastrointestinal tract. Over 6.3 million females and 14.2 million males in the United States between the ages of 20 and 74 have gallstones. Most patients with gallstones are asymptomatic but 10% of patients will develop symptoms within 5 years, and 20% of patients will develop symptoms within 20 years of diagnosing gallstones. Gallstone prevalence also increases with age. Over one-quarter of females older than the age of 60 will have gallstones. Gallstones have various compositions and etiologies.
Gallstones usually form from sluggishly emptying of bile from the gallbladder. When bile is not fully drained from the gallbladder, it can precipitate as sludge which in turn can develop into gallstones. Biliary obstruction from various causes such as strictures in the bile duct or neoplasms may also lead to gallstones. The most common cause of cholelithiasis is the precipitation of cholesterol from cholesterol-rich bile. The second most common form of gallstones is pigmented gallstones. These form from the breakdown of red blood cells and are black in color. The third type of gallstones is mixed pigmented stones which are a combination of calcium substrates such as calcium carbonate or calcium phosphate, cholesterol and bile. The fourth type of stones is calcium stones. These may be due to the precipitation of serum calcium in patients with hypercalcemia. Often these patients will have concurrent kidney stones.
Most gallstones are asymptomatic. In the United States, approximately 14 million women and 6 million men with an age range of 20 to 74 have gallstones. The prevalence increases as a person ages. Obesity increases the likelihood of gallstones, especially in women due to increases in biliary secretion of cholesterol. On the other hand, patients with drastic weight loss or fasting have a higher chance of gallstones secondary to biliary stasis. Furthermore, there is also a hormonal association with gallstones. Estrogen has been shown to result in an increase in bile cholesterol as well as a decrease in gallbladder contractility. Women of reproductive age or on birth control medication that have estrogen have a two-fold increase in gallstone formation compared to males. People with chronic illness such as diabetes also have an increase in gallstone formation as well as reduced gallbladder wall contractility due to neuropathy.
Gallstones occur when substances in the bile reach their limits of solubility. As bile becomes concentrated in the gallbladder, it becomes supersaturated with these substances, which in time precipitate into small crystals. These crystals, in turn, become stuck in the gallbladder mucus, resulting in gallbladder sludge. Over time, these crystals grow and form large stones. Complications caused by gallstones are a direct consequence of occlusion of the hepatic and biliary tree by sludge and stones.
Usually, patients with symptoms from gallstones present with right upper abdominal pain after eating greasy or spicy foods, nausea, and vomiting. Pain can also be present in the epigastric area that radiates to the right scapula or mid-back. The classic physical exam finding is a positive Murphy's sign, where the pain is elicited on deep palpation to the right upper quadrant underneath the rib cage upon deep inspiration. Patients may be asymptomatic for months to years until the discovery of gallstones. Acute cholecystitis presents similarly, however, is more severe. Jaundice can be a sign of a common bile duct obstruction from an entrapped gallstone. In the presence of jaundice and abdominal pain, often a procedure is an indication to go and retrieve the stone to prevent further sequelae. One such sequela is ascending cholangitis, with symptoms of right upper abdominal pain, fever, and jaundice (Charcot's triad). Progression of this condition is indicated by neurologic changes and hypotension (Reynold's pentad). Other sequelae are acute pancreatitis with symptoms of mid-epigastric pain and intractable vomiting.
The best diagnostic test for diagnosing gallstones and subsequent acute cholecystitis is a right upper quadrant abdominal ultrasound. It is associated with a 90% specificity rate and depending on the ultrasound operator, can detect stones as small as 2 mm as well as sludge and gallbladder polyps. Ultrasound findings that point towards acute cholecystitis versus cholelithiasis include gallbladder wall thickening (greater than 3 mm), pericholecystic fluid and a positive sonographic Murphy's sign. Gallstones can also often be present on CT scans and MRIs, however, these tests are not as sensitive for acute cholecystitis. Approximately 10% of gallstones may be found on routine plain films due to their high calcium content. If there is a suspected stone in the common bile duct based on ultrasound results, magnetic resonance cholangiopancreatography (MRCP) is the next step. If a common duct stone is identified on the MRCP, then the gold-standard test of an endoscopic retrograde cholangiopancreatogram (ERCP) should be performed by a gastroenterologist. A percutaneous transhepatic cholangiogram (PTHC) is also useful in diagnosing common bile duct stones if an ERCP is not possible.
Cholecystectomy treats symptomatic gallstones. The laparoscopic approach is the standard of care today. Open cholecystectomies are the option when it is not practical or advisable to do a laparoscopic procedure. It is not wise to only remove the gallstones as studies have shown that they recur after about one year. In cases of acute cholecystitis in critically ill patients or patients who are poor surgical candidates, a decompression cholecystostomy tube can be placed to temporize the patient until stable enough for definitive surgery. Common bile duct stones can be removed with a preoperative or postoperative ERCP, PTHC or operatively with a common bile duct exploration. Ascending cholangitis needs to be addressed urgently by removing the blockage either with ERCP, PTHC, or surgery, as well as early antibiotic administration. In cases of nonacute cholecystitis and very poor surgical candidates, gallstones can be treated medically. Ursodiol is administered daily with the hope of dissolving the gallstones and has shown mixed success with some studies at best showing less than a 50% response rate.
Gallbladder disease can be a difficult diagnosis. Early suspicion with proper testing will make the diagnosis. Having a skilled radiologist and emergency physician will often be the critical first steps in properly making the diagnosis of gallstones. Early intervention by an experienced surgeon is also vital. Practitioners should remember that not all gallstones will require surgery and the correct clinical decision must be made as a group recommendation between the primary care physician, nurse practitioner, radiologist, gastroenterologist, the patient, and the surgeon.
|||Tsai TJ,Chan HH,Lai KH,Shih CA,Kao SS,Sun WC,Wang EM,Tsai WL,Lin KH,Yu HC,Chen WC,Wang HM,Tsay FW,Lin HS,Cheng JS,Hsu PI, Gallbladder function predicts subsequent biliary complications in patients with common bile duct stones after endoscopic treatment? BMC gastroenterology. 2018 Feb 27 [PubMed PMID: 29486713]|
|||Rebholz C,Krawczyk M,Lammert F, Genetics of gallstone disease. European journal of clinical investigation. 2018 Jul [PubMed PMID: 29635711]|
|||Shabanzadeh DM, New determinants for gallstone disease? . Danish medical journal. 2018 Feb [PubMed PMID: 29393043]|
|||Del Pozo R,Mardones L,Villagrán M,Muñoz K,Roa S,Rozas F,Ormazábal V,Muñoz M, [Effect of a high-fat diet on cholesterol gallstone formation]. Revista medica de Chile. 2017 Sep [PubMed PMID: 29424395]|
|||Charfi S,Gouiaa N,Mnif H,Chtourou L,Tahri N,Abid B,Mzali R,Boudawara TS, Histopathological findings in cholecystectomies specimens: A single institution study of 20 584 cases. Hepatobiliary & pancreatic diseases international : HBPD INT. 2018 Aug [PubMed PMID: 30173787]|
|||Wilkins T,Agabin E,Varghese J,Talukder A, Gallbladder Dysfunction: Cholecystitis, Choledocholithiasis, Cholangitis, and Biliary Dyskinesia. Primary care. 2017 Dec [PubMed PMID: 29132521]|
|||[PubMed PMID: 30045318]|
|||[PubMed PMID: 29183521]|
|||[PubMed PMID: 29380173]|