Physiology, Gallbladder

Article Author:
Mark Jones
Article Author:
Kaitlynn Small
Article Author:
Sarang Kashyap
Article Editor:
Jeffrey Deppen
4/21/2020 4:44:33 PM
PubMed Link:
Physiology, Gallbladder


The gallbladder is a part of the biliary system. The biliary system involves the liver, with its vast blood supply, the gallbladder, and the hepatic and bile ducts. There are intrahepatic and extrahepatic components of the biliary system. The gallbladder is a part of the extrahepatic biliary system where bile is stored and concentrated. Bile is essential for digesting fats and is found in most animals, including mammals and reptiles. The gallbladder is located in the right upper quadrant of the abdomen affixed to the undersurface of the liver at the gallbladder fossa. It is about the size of a small pear and is attached to the extrahepatic biliary system via the cystic duct. Bile is formed in the liver. The intrahepatic ducts then collect it into the common hepatic duct. The bile then gets stored in the gallbladder through the cystic duct. When the gallbladder is stimulated to empty by food in the stomach and duodenum, it contracts and empties the concentrated bile back through the cystic duct, down the common bile duct, through the ampulla Vater, and into the second portion of the duodenum. Bile flow is also controlled by the opening and closing of the sphincter of Oddi at the ampulla Vater.

Issues of Concern

A mechanical dysfunctioning of gallbladder emptying is caused by a physical blockage, usually from a gallstone. Many factors produce gallstones. A high concentration of cholesterol in the bile can cause precipitation of the cholesterol in the form of cholesterol stones. High bile salt concentrations and high calcium concentrations can also result in gallstone formation. These gallstones can cause direct irritation of the gallbladder or a mechanical blockage of the cystic duct when the gallbladder is stimulated to empty. Hypokinetic functioning of the gallbladder can lead to a static state of gallbladder bile also precipitating to sludge and gallstones. Chronic acalculous cholecystitis is caused by the hypokinetic emptying of the gallbladder in response to food in the stomach. Gallstones and sludge are not present, but the symptoms are felt to be initiated by the inability of the gallbladder to empty sufficiently. Most of the time if patients present with some form of gallbladder pathology surgical intervention is indicated. Laparoscopic cholecystectomies are one of the most common surgical procedures done in modern times. Approximately 500,000 cholecystectomies are done yearly in the United States.


The liver is composed of the left and right lobes. The capsule of Glisson is a fibrous layer surrounding the surface of the liver. There are 8 functioning segments of the liver divided by each segment's blood supply. The liver has two main blood supplies. The majority of the blood supply (75%) comes from the portal vein. The remainder of its blood supply is from the left and right hepatic arteries which originate from the common hepatic artery which is a branch off of the left gastric artery. The cystic artery, which is the blood supply to the gallbladder, usually originates from the right hepatic artery. Hepatic lobules are the hexagonally shaped units of the liver. They contain a central vein in the middle and hepatocytes arranged from the central vein radiating to the periphery of the lobule. Epithelial lined liver sinusoids are located at the periphery of the hepatocytes. The hepatic lobular function is that mixed arterial and venous blood flows from the central vein peripherally and bile flows centrally to peripherally and is collected in the peripheral sinusoids. Hepatocytes constitute approximately 80% of the total liver volume. They are polyhedral shaped and usually contain one or two spherical nuclei and a single nucleolus. The cytoplasm is rich in RER, glycogen, SER, lysosomes and many mitochondria and Golgi apparatus. Another more poorly defined unit of the liver is acinus of Rappaport. These are three regions surrounding a distributing artery. They are classified into three zones and are described in a relationship from closer to more distant from the supplying central artery. Canals of Hering or terminal ductules are collecting ductules that bring bile to ductules in the portal canal. Kupffer cells are hepatic macrophages. They lie within the sinusoidal lumen near the portal tracts. They contain vacuoles and respond to liver injury by proliferating and enlarging. The space of Disse is located between the hepatocytes and the cells lining the sinusoids. This is an area of intercellular exchange and contains plasma and hepatic stellate and pit cells. Hepatic stellate or Ito cells store fat, and vitamin A. Pit cells have recently been identified by electron microscopy and are felt to act as killer cells in situations of liver assault or damage.

The liver parenchyma is further broken into portal tracts. Each portal tract contains a branch of the hepatic artery and portal vein. In addition, there is a bile ductule a bile duct and a lymphatic channel. Bile ductules are located at the periphery of the portal tract and are lined with low columnar or cuboid epithelium where larger bile ducts are lined with tall columnar epithelium.

The gallbladder wall is composed of several layers. The innermost layer is made up of columnar epithelium arranged in a microvillous formation, somewhat like the lining of the intestine. The other layers are the lamina propria, smooth muscularis, and serosa. Rotitansky-Aschoff sinuses are deep inclusions from the mucosal layer extending into the muscularis layer.[1]


The gallbladder and biliary system develop in the foregut. By the end of the fourth week of embryogenesis, the hepatic diverticulum out pouches from the developing duodenum. The hepatic diverticulum goes on to become the liver, extrahepatic biliary tree, and a portion of the pancreas. A second outpouching, known as the cystic diverticulum, immediately below develops into the gallbladder. The common bile duct becomes elongated and is recognizable by the end of the fifth week. It also undergoes plugging and recanalization of the lumen during this time. At week 6, the common bile duct and pancreas rotate 180 degrees around the duodenum. At week ten the sphincter of Oddi undergoes further development and differentiation of its musculature. At week 12, the bile ducts are patent and developed, and the liver and pancreas are secreting fluid into the duodenum. The musculature is almost totally developed around the external biliary system by week 28. Due to plugging and recanalizations of ducts and a 180-degree rotation of several organs of the foregut, development of the biliary tree is extremely diverse and complicated in humans. This leads to numerous variations of the biliary system that the surgeon must appreciate.[2]

Organ Systems Involved

Related organ systems that affect gallbladder physiology include the stomach and duodenum, the pancreas and the liver. Bile is formed in the liver which is then stored and concentrated in the gallbladder. High concentrations of bile salts, cholesterol or calcium, can result in the formation of gallstones. Distension of the stomach and duodenum with fatty foods causes the gallbladder to empty the bile into the duodenum. Situations of a prolonged period of the patient taking nothing by mouth or starvation can lead to inflammation of the gallbladder and the formation of gallstones. Pancreatitis can be the result of passed gallbladder sludge or stones or can lead to gallbladder issues by causing an outlet obstruction of the bile duct either due to a neoplasm or from inflammation.anatomy liver[3]


The function of the gallbladder is to store and concentrate bile (30 ml to 50 ml), which is released during the digestive and absorptive processes into the intestine. Contraction of the gallbladder with the release of bile into the biliary tree and duodenum is caused by gastric distension and fatty food content. This stimulates the secretion of cholecystokinin (CCK) from inclusion cells of the duodenum which causes contraction of the gallbladder. Neurostimulation of the gallbladder is from the hepatic branch of the anterior vegas nerve. Disruption of neuro innervation, blockage of the cystic duct from gallstones, or other etiologies can cause symptoms of chronic or acute cholecystitis. Tests such as a nuclear HIDA (hepatobiliary) scan with CCK, or ultrasound are used to diagnose gallbladder disease. The gallbladder is distensible, and when the cystic duct is obstructed, it can enlarge to twice its size. This may result in infection and inflammation requiring surgical removal.[3]

Related Testing

The test of choice to diagnose chronic cholecystitis is the abdominal ultrasound. This is noninvasive and can accurately evaluate the gallbladder for a thickened wall or inflammation. It is also the best test to diagnose gallstones or sludge. Calcified gallstones are only seen on plain abdominal x-rays in 10% of patients with cholelithiasis. Often a CT scan is done during an emergency department visit for abdominal pain. This is also very accurate when diagnosing gallbladder disease but may require IV and or oral contrast and does expose the patient to radiation. The best diagnostic test to confirm acalculous cholecystitis is the HIDA scan (hepatobiliary) with KINAVAC (CCK- cholecystokinin). This is a radionuclide scan where a tracer is given intravenously. This gets concentrated in the gallbladder. KINAVAC is then administered and the percent that the gallbladder empties (ejection fraction- EF) is calculated. An EF below 35% is considered abnormal and indicative of acalculous chronic cholecystitis. A complete blood count (CBC) might show an elevated white blood cell count (WBC) in cases of acute cholecystitis but is usually normal in chronic cholecystitis cases. A complete metabolic panel (CMP) may show elevated direct bilirubin in situations where there is an obstruction of the bile duct but is also usually normal in the setting of chronic cholecystitis.gallbladder testing[4]


Chronic Calculous Cholecystitis

Occlusion of the cystic duct or malfunction of the mechanics of the gallbladder emptying is the pathophysiology of this disease. Gallstones form from various materials such as bilirubinate or cholesterol. These materials increase the likelihood of cholecystitis and cholelithiasis in conditions such as sickle cell disease where red blood cells are broken down forming excess bilirubin and forming pigmented stones. Patients with excessive calcium such as in hyperparathyroidism can form calcium stones. Patients with excessive cholesterol can form cholesterol stones. Occlusion of the common bile duct such as in neoplasms or strictures can also lead to stasis of the bile flow causing gallstone formation with resultant chronic cholecystitis.

Acalculous Cholecystitis

Stasis of the gallbladder results in the build-up of intraluminal pressure. This eventually results in ischemia of the gallbladder wall and inflammation. This stasis can also lead to the colonization of bacteria which contributes to the inflammatory response. If the pressure is not relieved, the gallbladder wall will become progressively ischemic eventually resulting in gangrenous changes and perforation. This will lead to sepsis and shock. These findings are referred to as acute cholecystitis. Chronic acalculous cholecystitis is less insidious. Symptoms are more prolonged and less severe. The mechanism is the same, but it has not progressed to the findings associated with acute acalculous cholecystitis. Symptoms can also be more intermittent and vague, although often patients can present with signs of acute biliary cholic.gallbladder pathology[5]

Clinical Significance

Disruption or malfunction of the gallbladder's normal physiology can result in significant medical issues. Over 20 million Americans have gallstones. There are approximately 500,000 cholecystectomies done yearly in the United Stated for gallbladder disease. Many factors increase the risk for gallstone formation and gallbladder disease. The classic chronic cholecystitis patient is fat, 40, fertile, and female. The incidence of gallstone formation increases yearly with age. Over one-quarter of women older than the age of 60 will have gallstones. 

Most gallstones are asymptomatic. In the United States, approximately 14 million men and 6 million women with 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 2-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.

Fortunately today most cholecystectomies are performed laparoscopically. This affords a very low, less than 1%, complication rate with a fast recovery. Most patients can resume normal activities within 1 week after surgery. There is also a high rate of resolution (95%) of preoperative symptoms.[6]


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