Gallbladder

• 1. Introduction

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  The gallbladder turns up in the mummy of Princess Amenen of Thebes, whose remains date to 1500 BCE, in the form of gallstones. This small pouch beneath the liver has troubled people for thousands of years. Most people never think about it until it hurts.

  What does this pouch actually do all day? How did anatomists and surgeons come to understand it, and why can a person live without it? And why do both English and Chinese reach for this organ when they describe courage?

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• 2. A Pear Beneath the Liver

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  A fully stretched adult gallbladder measures about 7-10 cm in length and 4 cm across, with room for roughly 50 ml. It is a grey-blue organ resting in a shallow hollow under the right lobe of the liver. Its shape is a pear, and the narrow tip opens into the cystic duct.

  Anatomists divide the pear into three parts. The fundus is the rounded base, angled toward the abdominal wall. The body lies in a depression on the underside of the liver. The neck tapers and runs straight into the cystic duct, which belongs to the biliary tree. That duct then joins the common hepatic duct, and together they become the common bile duct.

  Where the neck meets the cystic duct, the wall bulges outward into a mucosal fold called Hartmann's pouch. Lymph drainage follows the cystic node, which sits between the cystic duct and the common hepatic duct. Lymph from the lower part of the organ passes through lower hepatic nodes. All of it finally reaches the celiac lymph nodes.

  Inside the wall, a single layer of columnar cells carries a brush border of microvilli, much like the absorptive cells of the intestine. Beneath that lie a lamina propria, a muscular layer, an outer perimuscular layer and the serosa. Unlike the rest of the gut, the gallbladder has no muscularis mucosae. The mucosa gathers into tiny folds called rugae, and small indentations known as Luschka's crypts mark its surface.

  Deep pockets called Rokitansky-Aschoff sinuses can push right through the muscle layer, and their presence points to adenomyomatosis. The muscle itself is smooth, with fibres running in longitudinal, oblique and transverse directions rather than in tidy layers. Connective and fat tissue wrap around it. The fundus, along with any surface that does not touch the liver, wears a thick serosa that is exposed to the peritoneum and carries blood vessels and lymphatics. Surfaces pressed against the liver are covered with connective tissue instead.

  Those muscle fibres do the squeezing, and a signal from the intestine tells them when to begin.

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• 3. Thickening the Bile

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  Between 30 and 60 ml of bile sits in the gallbladder at any one time. The liver makes it, and it travels through small vessels into the larger hepatic ducts. From there it flows down the cystic duct into the pouch, where it waits.

  A meal containing fat sets the process in motion. Fat entering the digestive tract makes I cells of the duodenum and jejunum release cholecystokinin, known as CCK. In response, the gallbladder contracts rhythmically and pushes bile into the common bile duct, which drains into the duodenum.

  In the duodenum, bile emulsifies the fats in partly digested food so the body can absorb them. It is made up mainly of water and bile salts. It also carries bilirubin, a product of hemoglobin metabolism, out of the body.

  A three- to tenfold concentration takes place during storage. The lining actively transports sodium and chloride ions across the epithelium, and the osmotic pressure this creates draws water and other electrolytes out with them. The bile that leaves the gallbladder is therefore not the same fluid that arrived from the liver.

  A meta-analysis of eighteen studies hints at a further job, protection against cancer. It concluded that removing the gallbladder harms the risk of right-sided colon cancer. A more recent study reported a significantly higher overall cancer risk, spread across several types of cancer, after removal.

  Not every gallbladder is built to the same plan, though, and a few people are born with a very different arrangement.

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• 4. Doubles and Absences

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  Two, or even three, gallbladders can coexist in one person, though this is rare. They may drain as separate bladders into the cystic duct, or share a common branch that does. Some gallbladders have two lobes divided by a septum, and some people never form one at all. These abnormalities are generally silent and unlikely to affect function.

  Position varies as well. Documented cases place the organ within the liver, above it, on its left side, behind it, or detached and hanging from it. From 1886 to 1998, only 110 cases of left-lying liver were reported in the scientific literature, fewer than one per year.

  A Phrygian cap is a harmless fold in the fundus, named because it looks like a Phrygian cap.

  The organ's origins lie in the second week of embryonic life. The human embryo, which has three germ layers and sits against a yolk sac, begins to wrap itself around parts of that sac. The wrapped portions become the basis of the adult digestive tract. The foregut then starts to differentiate into the esophagus, stomach and intestines.

  In the fourth week, the stomach rotates away from the midline until its body lies on the left. By the end of that week, the developing duodenum sprouts a hepatic diverticulum on its right side, which will become the biliary tree. Just below it appears a second outpouching, the cystic diverticulum, and this becomes the gallbladder. The organ therefore begins as a pocket of endoderm budding from the embryonic gut tube.

  Most vertebrates have a gallbladder, but the plumbing differs. In many species, several separate ducts run to the intestine instead of the single common bile duct found in humans.

  Bile from several species of bears is used in traditional Chinese medicine. Bile bears are kept alive in captivity while their bile is extracted, in an industry characterized by animal cruelty.

  Horses, deer and giraffes manage without a gallbladder, as do many rodents and laminoids. So do pigeons and some psittacine species, along with lampreys and all invertebrates. That list of animals living without the organ would later persuade a surgeon to take a bold step.

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• 5. Stones and Inflammation

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  Cholesterol and bilirubin are the usual raw materials of gallstones, which form when bile becomes saturated with one of them. Most stones cause no symptoms. They either stay in the gallbladder or pass along the biliary system. When symptoms do come, the pain is severe and colicky, felt in the upper right quadrant of the abdomen.

  Where a stone lodges decides the trouble that follows. A stone that blocks the gallbladder can cause the inflammation called cholecystitis. One stuck in the biliary system may cause jaundice, and one that blocks the pancreatic duct may cause pancreatitis.

  Ultrasound is the tool used to diagnose gallstones. A symptomatic stone is often managed by waiting for it to pass naturally. Because stones tend to come back, surgery to remove the gallbladder is often considered. The medication ursodeoxycholic acid may be used, and so may lithotripsy, a non-invasive mechanical procedure that breaks the stones apart.

  In cholecystitis, trapped bile accumulates and pressure on the gallbladder wall may release inflammatory substances such as phospholipase. Bacterial infection is a further risk. The patient may have sharp, localised pain with fever and tenderness in the upper right abdomen, and may show a positive Murphy's sign. Rest and antibiotics are the usual management, particularly cephalosporins and, in severe cases, metronidazole. If inflammation has progressed far enough, the gallbladder may need to come out surgically.

  A full blood count is one of the first investigations, since a raised white cell count suggests inflammation or infection. Bilirubin and liver function tests reveal whether the trouble involves the biliary tree or the liver itself, and bilirubin rises when bile flow is obstructed. An elevated lipase or amylase may indicate pancreatitis. A CA 19-9 level may be taken to investigate for cholangiocarcinoma.

  Beyond ultrasound, the imaging options include an abdominal X-ray or CT scan, MRCP, ERCP, and percutaneous or intraoperative cholangiography. A cholescintigraphy scan is a nuclear imaging procedure used to judge the condition of the gallbladder.

  A gallbladder with stones, polyps or a calcified wall can also carry a darker possibility.

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• 6. Cancer and Polyps

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  Cancer of the gallbladder is uncommon and mostly appears in later life. When it does occur, it is usually an adenocarcinoma of the glands lining the surface. Gallstones are thought to be linked to its formation. Other risk factors are polyps larger than 1 cm and a highly calcified "porcelain" gallbladder.

  Attacks of biliary pain, jaundice and weight loss are the warning signs. A large gallbladder may even be felt in the abdomen. Liver function tests may be elevated, particularly GGT and ALP, and ultrasound and CT scans are the imaging investigations of choice.

  Removal of the gallbladder is the management, yet as of 2010 the prognosis remained poor. In 13% of cases, the cancer is found by chance after a gallbladder has been removed for another reason.

  Polyps are mostly benign growths, or lesions that resemble growths, in the gallbladder wall. They are tied to cancer only when they are large. Cholesterol polyps are often associated with cholesterolosis, nicknamed the "strawberry gallbladder", a change in the wall caused by excess cholesterol. They usually cause no symptoms, so they are frequently found by accident.

  Removing the organ has a history of its own, and it starts well before any surgeon picked up a knife.

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• 7. Centuries of Surgery

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  Babylonian models of the gallbladder and biliary tree survive from 2000 BCE, and an Etruscan model dates to 200 BCE. Both are associated with divine worship. Some historians believe the death of Alexander the Great may have involved an acute episode of cholecystitis.

  The existence of the organ has been noted since the 5th century. Its function and diseases, however, have been documented only in the last two centuries. The first descriptions of gallstones appear in the Renaissance. One explanation is that earlier diets, richer in cereals and vegetables and lower in meat, produced fewer stones.

  Anthonius Benevinius, in 1506, was the first to link symptoms with the presence of gallstones. In 1890, Ludwig Georg Courvoisier examined a number of cases and gave his name to a law. It states that when the gallbladder is enlarged and not tender, gallstones are an unlikely cause of jaundice.

  The physician Joenisius performed the first surgical removal of a gallstone in 1676. He took the stones from a biliary fistula that had formed on its own. Stough Hobbs carried out the first recorded cholecystotomy in 1867, although the French surgeon Jean Louis Petit had described the operation in the mid-18th century.

  Carl Langenbuch, a German surgeon, performed the first cholecystectomy in 1882 on a sufferer of cholelithiasis. Before him, surgery had aimed at creating a fistula to drain the stones. Langenbuch reasoned that several other mammals have no gallbladder, so humans could survive without one.

  The 1920s settled a debate over whether to remove the gallbladder or only its stones, and the consensus favoured removing the gallbladder. Imaging with contrast medium and CT scans reached the gallbladder only in the mid and late twentieth century. Erich Mühe of Germany performed the first laparoscopic cholecystectomy in 1985. French surgeons Phillipe Mouret and Francois Dubois are often credited for their operations in 1987 and 1988.

  Today a cholecystectomy is considered an elective procedure, done openly or laparoscopically. The gallbladder is taken out from neck to fundus, so bile drains straight from the liver into the biliary tree. About 30 percent of patients feel some indigestion afterward. Severe complications are much rarer, but about 10 percent of operations lead to a chronic condition called postcholecystectomy syndrome.

  Biliary injury is damage to the bile ducts, most commonly an iatrogenic complication of cholecystectomy. The risk is higher with laparoscopic surgery than with open surgery. Left undiagnosed or poorly managed, it may cause death, so it is ideally treated at a center with endoscopy, radiology and surgical expertise.

  A biloma is a collection of bile within the abdominal cavity, caused by a bile leak. After gallbladder removal its incidence is 0.3-2%. Other causes include biliary surgery, liver biopsy, abdominal trauma and, rarely, spontaneous perforation.

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• 8. Gall and Judgement

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  In English, having gall suggests bold, belligerent behaviour, while having bile suggests sourness. The two words come from the same fluid, yet they point in opposite emotional directions.

  In traditional Chinese medicine, the gallbladder is associated with the Wuxing element of wood. In excess, its emotion is belligerence, and in deficiency it is cowardice. The language is full of idioms built on the organ.

  One idiom describes a forward person as having "a body completely of gall". Another names a lone hero as a "single, alone gallbladder hero". A third is used to say that someone has a lot of gall to talk the way they do.

  In the Zangfu theory of Chinese medicine, the gallbladder is an extraordinary Fu organ, classed as yang because it holds bile. The theory credits it with more than digestion. It is seen as the seat of decision-making and judgement, so the organ that holds bile is also thought to hold the capacity to judge.

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