Gallbladder disease

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Gallbladder disease
Other names Biliary disease, Hepatobiliary disease
Gallbladder cholesterolosis intermed mag cropped.jpg
Micrograph of cholesterolosis of the gallbladder, a very common gallbladder disease. Cholecystectomy specimen. H&E stain.
Specialty Gastroenterology   OOjs UI icon edit-ltr-progressive.svg

Gallbladder diseases are diseases involving the gallbladder and is closely linked to biliary disease, with the most common cause being gallstones (cholelithiasis). [1] [2]

Contents

The gallbladder is designed to aid in the digestion of fats by concentrating and storing the bile made in the liver and transferring it through the biliary tract to the digestive system through bile ducts that connect the liver, gallbladder, and the Sphincter of Oddi. The gallbladder is controlled on a neurohormonal basis, with Cholecystokinin (CCK) leading to the contraction and release of bile into the bile ducts. Other hormones allow for the relaxation and further storing of bile. [3] [4] A disruption in the hormones, ducts, or gallbladder can lead to disease. Gallstones are the most common disease and can lead to other diseases, including Cholecystitis, inflammation of the gallbladder, and gallstone pancreatitis when the gallstone blocks the pancreatic duct. [1] [2] [5] Treatment is considered for symptomatic disease and can vary from surgical to non-surgical treatment. [2]

About 104 million new cases of gallbladder and biliary disease occurred in 2013. [6]

Signs and symptoms

Gallbladder disease presents chiefly with abdominal pain located in the right upper abdomen. This pain is described as biliary colic. Pain typically occurs suddenly and radiates to the right shoulder and back, depending on several factors, including specific diseases. It can either be constant or episodic and last from minutes to hours. This pain is described as biliary colic pain. Other common symptoms with gallbladder disease and biliary colic are nausea and vomiting. With conditions such as cholecystitis and choledocholithiasis, fever may be present. [1] [2]

During the physical examination, the patient will present with Murphy's sign. This maneuver requires the physician to grab the lower part of the right ribs and curl their fingers under them. A positive test elicits pain with deep inspiration and is indicative of inflammation of the gallbladder, cholecystitis. With positive Murphy's sign, deep palpation of the abdomen also elicits pain. In these cases, physicians will need to rule out peritonitis, inflammation of the abdominal cavity. A negative Murphy's sign does not rule out all gallbladder diseases as ascending cholangitis. Using an ultrasound transducer supplanting a physician's hands during an abdominal ultrasound can detect a positive Murphy's sign. The sign also has over a 90% positive and negative predictive value for acute cholecystitis [2] [7]

Gallstones

Gallstones may develop in the gallbladder as well as elsewhere in the biliary tract. If gallstones in the gallbladder are symptomatic, surgical removal of the gallbladder, known as cholecystectomy may be indicated.

Gallstones form when the tenuous balance of solubility of biliary lipids tips in favor of precipitation of cholesterol, unconjugated bilirubin, or bacterial degradation products of biliary lipids. For cholesterol gallstones, metabolic alterations in hepatic cholesterol secretion combine with changes in gallbladder motility and intestinal bacterial degradation of bile salts to destabilize cholesterol carriers in bile and produce cholesterol crystals. For black pigment gallstones, changes in heme metabolism or bilirubin absorption lead to increased bilirubin concentrations and precipitation of calcium bilirubinate. In contrast, mechanical obstruction of the biliary tract is the major factor leading to bacterial degradation and precipitation of biliary lipids in brown pigment stones. [8]

Risk factors

Pregnancy

During pregnancy when female sex hormones are naturally raised, biliary sludge (particulate material derived from bile that is composed of cholesterol, calcium bilirubinate, and mucin) appears in 5% to 30% of women. Resolution frequently transpires during the post-partum period: sludge disappears in two-thirds; small (<1 cm) gallstones (microlithiasis) vanish in one-third, but definitive gallstones become established in ~5%. Additional risk factors for stone formation during pregnancy include obesity (prior to the pregnancy), reduced high density lipoprotein (HDL) cholesterol and the metabolic syndrome. [9]

Hormonal contraceptives

Women are almost twice as likely as men to form gallstones especially during the fertile years; the gap narrows after the menopause. The underlying mechanism is female sex hormones; parity, oral contraceptive use and estrogen replacement therapy are established risk factors for cholesterol gallstone formation. Female sex hormones adversely influence hepatic bile secretion and gallbladder function. Estrogens increase cholesterol secretion and diminish bile salt secretion, while progestins act by reducing bile salt secretion and impairing gallbladder emptying leading to stasis. A new 4th generation progestin, drospirenone, used in some oral contraceptives may further heighten the risk of gallstone disease and cholecystectomy; however, the increased risk is quite modest and not likely to be clinically meaningful. [9]

A retrospective (historical) cohort study was performed on a very large data base including 1980 and 1981 Medicaid billing data from the states of Michigan and Minnesota in which 138,943 users of OCs were compared with 341,478 nonusers. Oral contraceptives were shown as risk factors for gallbladder disease, although the risk is of sufficient magnitude to be of potential clinical importance only in young women. [10]

The 1984 Royal College of General Practitioners' Oral Contraception Study suggests that, in the long-term, oral contraceptives are not associated with any increased risk of gallbladder disease, although there is an acceleration of the disease in those women susceptible to it. [11]

Newer research suggests otherwise. A 1993 meta-analysis concludes that oral contraceptive use is associated with a slightly and transiently increased rate of gallbladder disease, but laters confirms that modern low-dose oral contraceptives are safer than older formulas, though an effect cannot be excluded. [12]

A 2001 comparative study of the IMS LifeLink Health Plan Claims Database interpreted that in a large cohort of women using oral contraceptives, there was found a small, statistically significant increase in the risk of gallbladder disease associated with desogestrel, drospirenone and norethisterone compared with levonorgestrel. No statistically significant increase in risk was associated with the other formulations of oral contraceptive (etynodiol diacetate, norgestrel and norgestimate). [13]

Menopausal hormone therapy

While some observational studies had suggested that estrogens increase the risk for gallbladder disease by as much as twofold to fourfold, such an association had not been reported consistently. [14] [15] More recent randomized clinical trial data among postmenopausal women now support a causal role for oral menopausal hormone therapy estrogens. Confirming the positive finding of another large study, [16] the landmark Women's Health Initiative (WHI) reported very significant increases (p < 0.001) for risk of gallbladder disease or surgery attributed to treatments with both estrogen alone (conjugated equine estrogen; CEE) and estrogen-plus-progestin (conjugated equine estrogen with medroxyprogesterone; CEE+MPA ). Specifically, a 67% increase (CEE versus placebo) and 59% increase (CEE+MPA versus placebo) among healthy postmenopausal women that reported either having had a hysterectomy (n = 8376) or not (n = 14203) prior to randomization, respectively. [17]

Other factors

A prospective study in 1994 noted that body mass index remains the strongest predictor of symptomatic gallstones among young women. Other risk factors are having over four pregnancies, weight gain, and cigarette smoking. Alcohol was shown to have an inverse relationship between use and gallbladder disease. [18]

Diseases of the Gallbladder

Diagnosis

A diagnostic workup is based on the most likely diagnosis. In testing for gallbladder disease, specifically, liver panel tests and pancreatic enzymes such as lipase will be within normal limits. There can be a mild elevation in alkaline phosphatase and bilirubin in some instances, such as cholecystitis. If gallstones are blocking other biliary tract areas causing pancreatic gallstones or choledocholithiasis, elevated liver panel, pancreatic enzymes, and bilirubin will be noted. [1] [2]

Ultrasound is the diagnostic imaging of choice to examine for thickening of the gallbladder walls, polyps, pericholecystic fluid, and gallstones. A positive Murphy's sign may also be noted using the ultrasound transducer. [19] [7] Another imaging modality is using cholescintigraphy to examine hepatic function. This scan assesses if the gallbladder is functioning as it is supposed to with a controlled amount of hormone. [1] [19] In regards to a suspected choledocholithiasis, a endoscopic retrograde cholangiopancreatography (ERCP) is used in both the diagnosis and treatment as it can remove the stones that are blocking the bile ducts causing choledocholithiasis. [2]

Treatment

In patients with an asymptomatic disease where a gallstone or small polyp was found incidentally, no further treatment is undertaken until symptoms arise. When an individual has symptomatic gallbladder disease and early-stage cancer, a cholecystectomy is utilized. A cholecystectomy is controversial in advanced cancer due to the low 5-year survival rate, especially if regional lymph nodes are involved. [19] Symptoms of gallbladder disease typically decrease after cholecystectomy unless the abdominal pain was caused by other digestive tract diseases such as irritable bowel syndrome. [4]

Nonsurgical treatment of gallstones and cholecystitis includes medication therapy are used to dissolve the stones. Chenodeoxycholic acid and ursodiol with ursodiol more commonly used due to their side-effect profile. It will take approximately two years to dissolve small stones with medications. [4] [2] Other avenues to reduce the modifiable risk factors that one may have for gallstones by reducing weight, dietary changes to lower cholesterol, and triglycerides. [2]

See also

Related Research Articles

<span class="mw-page-title-main">Bile</span> Dark greenish-brown fluid aiding in the digestion of fats

Bile, or gall, is a dark-green-to-yellowish-brown fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is produced continuously by the liver and stored and concentrated in the gallbladder. After eating, this stored bile is discharged into the duodenum.

<span class="mw-page-title-main">Gallbladder</span> Organ in humans and other vertebrates

In vertebrates, the gallbladder, also known as the cholecyst, is a small hollow organ where bile is stored and concentrated before it is released into the small intestine. In humans, the pear-shaped gallbladder lies beneath the liver, although the structure and position of the gallbladder can vary significantly among animal species. It receives and stores bile, produced by the liver, via the common hepatic duct, and releases it via the common bile duct into the duodenum, where the bile helps in the digestion of fats.

<span class="mw-page-title-main">Bile duct</span> Type of organ

A bile duct is any of a number of long tube-like structures that carry bile, and is present in most vertebrates.

<span class="mw-page-title-main">Gallstone</span> Disease where stones form in the gallbladder

A gallstone is a stone formed within the gallbladder from precipitated bile components. The term cholelithiasis may refer to the presence of gallstones or to any disease caused by gallstones, and choledocholithiasis refers to the presence of migrated gallstones within bile ducts.

<span class="mw-page-title-main">Cholecystitis</span> Medical condition

Cholecystitis is inflammation of the gallbladder. Symptoms include right upper abdominal pain, pain in the right shoulder, nausea, vomiting, and occasionally fever. Often gallbladder attacks precede acute cholecystitis. The pain lasts longer in cholecystitis than in a typical gallbladder attack. Without appropriate treatment, recurrent episodes of cholecystitis are common. Complications of acute cholecystitis include gallstone pancreatitis, common bile duct stones, or inflammation of the common bile duct.

<span class="mw-page-title-main">Cholecystectomy</span> Surgical removal of the gallbladder

Cholecystectomy is the surgical removal of the gallbladder. Cholecystectomy is a common treatment of symptomatic gallstones and other gallbladder conditions. In 2011, cholecystectomy was the eighth most common operating room procedure performed in hospitals in the United States. Cholecystectomy can be performed either laparoscopically, or via an open surgical technique.

<span class="mw-page-title-main">Common bile duct</span> Gastrointestinal duct

The common bile duct, sometimes abbreviated as CBD, is a duct in the gastrointestinal tract of organisms that have a gallbladder. It is formed by the confluence of the common hepatic duct and cystic duct and terminates by uniting with pancreatic duct, forming the ampulla of Vater. The flow of bile from the ampulla of Vater into the duodenum is under the control of the sphincter of Oddi.

<span class="mw-page-title-main">Common bile duct stone</span> Medical condition

Common bile duct stone, also known as choledocholithiasis, is the presence of gallstones in the common bile duct (CBD). This condition can cause jaundice and liver cell damage. Treatments include choledocholithotomy and endoscopic retrograde cholangiopancreatography (ERCP).

<span class="mw-page-title-main">Gallbladder cancer</span> Medical condition

Gallbladder cancer is a relatively uncommon cancer, with an incidence of fewer than 2 cases per 100,000 people per year in the United States. It is particularly common in central and South America, central and eastern Europe, Japan and northern India; it is also common in certain ethnic groups e.g. Native American Indians and Hispanics. If it is diagnosed early enough, it can be cured by removing the gallbladder, part of the liver and associated lymph nodes. Most often it is found after symptoms such as abdominal pain, jaundice and vomiting occur, and it has spread to other organs such as the liver.

<span class="mw-page-title-main">Ascending cholangitis</span> Medical condition

Ascending cholangitis, also known as acute cholangitis or simply cholangitis, is inflammation of the bile duct, usually caused by bacteria ascending from its junction with the duodenum. It tends to occur if the bile duct is already partially obstructed by gallstones.

<span class="mw-page-title-main">Biliary colic</span> Medical condition in which gallstones cause acute pain

Biliary colic, also known as symptomatic cholelithiasis, a gallbladder attack or gallstone attack, is when a colic occurs due to a gallstone temporarily blocking the cystic duct. Typically, the pain is in the right upper part of the abdomen, and can be severe. Pain usually lasts from 15 minutes to a few hours. Often, it occurs after eating a heavy meal, or during the night. Repeated attacks are common.

<span class="mw-page-title-main">Biliary tract</span> Organ system

The biliary tract, refers to the liver, gallbladder and bile ducts, and how they work together to make, store and secrete bile. Bile consists of water, electrolytes, bile acids, cholesterol, phospholipids and conjugated bilirubin. Some components are synthesized by hepatocytes, the rest are extracted from the blood by the liver.

<span class="mw-page-title-main">Cholescintigraphy</span> Medical imaging of hepatobiliary tract using radiotracers

Cholescintigraphy or hepatobiliary scintigraphy is scintigraphy of the hepatobiliary tract, including the gallbladder and bile ducts. The image produced by this type of medical imaging, called a cholescintigram, is also known by other names depending on which radiotracer is used, such as HIDA scan, PIPIDA scan, DISIDA scan, or BrIDA scan. Cholescintigraphic scanning is a nuclear medicine procedure to evaluate the health and function of the gallbladder and biliary system. A radioactive tracer is injected through any accessible vein and then allowed to circulate to the liver, where it is excreted into the bile ducts and stored by the gallbladder until released into the duodenum.

<span class="mw-page-title-main">Gallbladder polyp</span> Medical condition

Gallbladder polyps are growths or lesions resembling growths in the wall of the gallbladder. True polyps are abnormal accumulations of mucous membrane tissue that would normally be shed by the body.

<span class="mw-page-title-main">Sphincter of Oddi dysfunction</span> Medical condition

Sphincter of Oddi dysfunction refers to a group of functional disorders leading to abdominal pain due to dysfunction of the Sphincter of Oddi: functional biliary sphincter of Oddi and functional pancreatic sphincter of Oddi disorder. The sphincter of Oddi is a sphincter muscle, a circular band of muscle at the bottom of the biliary tree which controls the flow of pancreatic juices and bile into the second part of the duodenum. The pathogenesis of this condition is recognized to encompass stenosis or dyskinesia of the sphincter of Oddi ; consequently the terms biliary dyskinesia, papillary stenosis, and postcholecystectomy syndrome have all been used to describe this condition. Both stenosis and dyskinesia can obstruct flow through the sphincter of Oddi and can therefore cause retention of bile in the biliary tree and pancreatic juice in the pancreatic duct.

<span class="mw-page-title-main">Biliary sludge</span> Medical condition

Biliary sludge refers to a viscous mixture of small particles derived from bile. These sediments consist of cholesterol crystals, calcium salts, calcium bilirubinate, mucin, and other materials.

<span class="mw-page-title-main">Adenomyomatosis</span> Medical condition

Adenomyomatosis is a benign condition characterized by hyperplastic changes of unknown cause involving the wall of the gallbladder. Adenomyomatosis is caused by an overgrowth of the mucosa, thickening of the muscular wall, and formation of intramural diverticula or sinus tracts termed Rokitansky–Aschoff sinuses, also called entrapped epithelial crypts.

<span class="mw-page-title-main">Choledochoduodenostomy</span>

Choledochoduodenostomy (CDD) is a surgical procedure to create an anastomosis, a surgical connection, between the common bile duct (CBD) and an alternative portion of the duodenum. In healthy individuals, the CBD meets the pancreatic duct at the ampulla of Vater, which drains via the major duodenal papilla to the second part of duodenum. In cases of benign conditions such as narrowing of the distal CBD or recurrent CBD stones, performing a CDD provides the diseased patient with CBD drainage and decompression. A side-to-side anastomosis is usually performed.

Hyperbilirubinemia is a clinical condition describing an elevation of blood bilirubin level due to the inability to properly metabolise or excrete bilirubin, a product of erythrocytes breakdown. In severe cases, it is manifested as jaundice, the yellowing of tissues like skin and the sclera when excess bilirubin deposits in them. The US records 52,500 jaundice patients annually. By definition, bilirubin concentration of greater than 3 mg/ml is considered hyperbilirubinemia, following which jaundice progressively develops and becomes apparent when plasma levels reach 20 mg/ml. Rather than a disease itself, hyperbilirubinemia is indicative of multifactorial underlying disorders that trace back to deviations from regular bilirubin metabolism. Diagnosis of hyperbilirubinemia depends on physical examination, urinalysis, serum tests, medical history and imaging to identify the cause. Genetic diseases, alcohol, pregnancy and hepatitis viruses affect the likelihood of hyperbilirubinemia. Causes of hyperbilirubinemia mainly arise from the liver. These include haemolytic anaemias, enzymatic disorders, liver damage and gallstones. Hyperbilirubinemia itself is often benign. Only in extreme cases does kernicterus, a type of brain injury, occur. Therapy for adult hyperbilirubinemia targets the underlying diseases but patients with jaundice often have poor outcomes.

References

  1. 1 2 3 4 5 Corazziari, E; Shaffer, E A; Hogan, W J; Sherman, S; Toouli, J (1 September 1999). "Functional disorders of the biliary tract and pancreas". Gut. 45 (Supplement 2): ii48–ii54. doi: 10.1136/gut.45.2008.ii48 . PMC   1766688 . PMID   10457045.
  2. 1 2 3 4 5 6 7 8 9 Afamefuna, Simore Candidate Philadelphia College of Osteopathic Medicine School of Pharmacy Suwanee, Georgia Shari N. Allen, PharmD, BCPP Assistant Professor of Pharmacy Practice Philadelphia College of Osteopathic Medicine School of Pharmacy Suwanee (2013). "Gallbladder Disease: Pathophysiology, Diagnosis, and Treatment". US Pharm. 38 (3): 33-41.
  3. ↑ Luo, Xiaoyu (2007). "On the mechanical behavior of the human biliary system". World Journal of Gastroenterology. 13 (9): 1384–1392. doi:10.3748/wjg.v13.i9.1384. PMC   4146923 . PMID   17457970.
  4. 1 2 3 4 Behar, Jose (24 February 2013). "Physiology and Pathophysiology of the Biliary Tract: The Gallbladder and Sphincter of Oddi—A Review". ISRN Physiology. 2013: 1–15. doi: 10.1155/2013/837630 .
  5. 1 2 3 4 Stinton, Laura M.; Shaffer, Eldon A. (15 April 2012). "Epidemiology of Gallbladder Disease: Cholelithiasis and Cancer". Gut and Liver. 6 (2): 172–187. doi:10.5009/gnl.2012.6.2.172. PMC   3343155 . PMID   22570746.
  6. ↑ Global Burden of Disease Study 2013, Collaborators (22 August 2015). "Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013". Lancet. 386 (9995): 743–800. doi:10.1016/S0140-6736(15)60692-4. PMC   4561509 . PMID   26063472.{{cite journal}}: |first1= has generic name (help)
  7. 1 2 Salati, Sajad; al Kadi, Azzam (2012). "Murphy's sign of cholecystitis-a brief revisit". Journal of Symptoms and Signs. 1 (2): 53-56.
  8. ↑ Donovan, J. M. (1999). "Physical and metabolic factors in gallstone pathogenesis". Gastroenterology Clinics of North America. 28 (1): 75–97. doi:10.1016/s0889-8553(05)70044-3. PMID   10198779.
  9. 1 2 Stinton LM, Shaffer EA (2012). "Epidemiology of gallbladder disease: cholelithiasis and cancer". Gut Liver. 6 (2): 172–87. doi:10.5009/gnl.2012.6.2.172. PMC   3343155 . PMID   22570746.
  10. ↑ Strom, B. L.; Tamragouri, R. N.; Morse, M. L.; Lazar, E. L.; West, S. L.; Stolley, P. D.; Jones, J. K. (1986). "Oral contraceptives and other risk factors for gallbladder disease". Clinical Pharmacology and Therapeutics. 39 (3): 335–41. doi:10.1038/clpt.1986.49. PMID   3948473. S2CID   10820333.
  11. ↑ Kay, C. R. (1984). "The Royal College of General Practitioners' Oral Contraception Study: Some recent observations". Clinics in Obstetrics and Gynaecology. 11 (3): 759–86. doi:10.1016/S0306-3356(21)00626-9. PMID   6509858.
  12. ↑ Thijs C, Knipschild P (1993). "Oral contraceptives and the risk of gallbladder disease: a meta-analysis". Am J Public Health. 83 (8): 1113–20. doi:10.2105/ajph.83.8.1113. PMC   1695167 . PMID   8342719.
  13. ↑ Etminan M, Delaney JA, Bressler B, Brophy JM (2011). "Oral contraceptives and the risk of gallbladder disease: a comparative safety study". CMAJ. 183 (8): 899–904. doi:10.1503/cmaj.110161. PMC   3091897 . PMID   21502354.
  14. ↑ Diehl, A. K. (March 1991). "Epidemiology and natural history of gallstone disease". Gastroenterology Clinics of North America. 20 (1): 1–19. doi:10.1016/S0889-8553(21)00531-8. ISSN   0889-8553. PMID   2022415.
  15. ↑ Uhler, M. L.; Marks, J. W.; Judd, H. L. (May 2000). "Estrogen replacement therapy and gallbladder disease in postmenopausal women". Menopause. 7 (3): 162–167. doi:10.1097/00042192-200007030-00006. ISSN   1072-3714. PMID   10810961. S2CID   37022601.
  16. ↑ Simon, J. A.; Hunninghake, D. B.; Agarwal, S. K.; Lin, F.; Cauley, J. A.; Ireland, C. C.; Pickar, J. H. (2001-10-02). "Effect of estrogen plus progestin on risk for biliary tract surgery in postmenopausal women with coronary artery disease. The Heart and Estrogen/progestin Replacement Study". Annals of Internal Medicine. 135 (7): 493–501. doi:10.7326/0003-4819-135-7-200110020-00008. ISSN   0003-4819. PMID   11578152. S2CID   43020058.
  17. ↑ Cirillo, Dominic J.; Wallace, Robert B.; Rodabough, Rebecca J.; Greenland, Philip; LaCroix, Andrea Z.; Limacher, Marian C.; Larson, Joseph C. (2005-01-19). "Effect of estrogen therapy on gallbladder disease" (PDF). JAMA. 293 (3): 330–339. doi: 10.1001/jama.293.3.330 . ISSN   1538-3598. PMID   15657326.
  18. ↑ Grodstein, F; Colditz, G. A.; Hunter, D. J.; Manson, J. E.; Willett, W. C.; Stampfer, M. J. (1994). "A prospective study of symptomatic gallstones in women: Relation with oral contraceptives and other risk factors". Obstetrics and Gynecology. 84 (2): 207–14. PMID   8041531.
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  20. 1 2 Makino, Isamu; Yamaguchi, T; Sato, N; Yasui, T; Kita, I (2009). "Xanthogranulomatous cholecystitis mimicking gallbladder carcinoma with a false-positive result on fluorodeoxyglucose PET". World Journal of Gastroenterology. 15 (29): 3691–3. doi:10.3748/wjg.15.3691. PMC   2721248 . PMID   19653352.
  21. ↑ Rao, RV; Kumar, A; Sikora, SS; Saxena, R; Kapoor, VK (2005). "Xanthogranulomatous cholecystitis: Differentiation from associated gall bladder carcinoma". Tropical Gastroenterology. 26 (1): 31–3. PMID   15974235.
  22. ↑ McCoy Jr, JJ; Vila, R; Petrossian, G; McCall, RA; Reddy, KS (1976). "Xanthogranulomatous cholecystitis. Report of two cases". Journal of the South Carolina Medical Association. 72 (3): 78–9. PMID   1063276.
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