Preliminary Research


(Science: anatomy) a digestive organ which stores bile (produced in the liver), used in the digestion and absorption of fats in the duodenum. A muscular sac attached to the liver that secretes bile and stores it until needed for digestion.

Secretion of Bile and the Role of Bile Acids In Digestion

Bile is a complex fluid containing water, electrolytes and a battery of organic molecules including bile acids, cholesterol, phospholipids and bilirubin that flows through the biliary tract into the small intestine. There are two fundamentally important functions of bile in all species:

  • Bile      contains bile acids, which are critical for digestion and absorption of      fats and fat-soluble vitamins in the small intestine.
  • Many      waste products are eliminated from the body by secretion into bile and      elimination in feces.

Adult humans produce 400 to 800 ml of bile daily, and other animals proportionately similar amounts. The secretion of bile can be considered to occur in two stages:

  • Initially,      hepatocytes secrete bile into canaliculi, from which it flows into bile      ducts. This hepatic bile contains large quantities of bile acids,      cholesterol and other organic molecules.
  • As      bile flows through the bile ducts it is modified by addition of a watery,      bicarbonate-rich secretion from ductal epithelial cells.

In species with a gall bladder (man and most domestic animals except horses and rats), further modification of bile occurs in that organ. The gall bladder stores and concentrates bile during the fasting state. Typically, bile is concentrated five-fold in the gall bladder by absorption of water and small electrolytes – virtually all of the organic molecules are retained.

Secretion into bile is a major route for eliminating cholesterol. Free cholesterol is virtually insoluble in aqueous solutions, but in bile, it is made soluble by bile acids and lipids like lethicin. Gallstones, most of which are composed predominantly of cholesterol, result from processes that allow cholesterol to precipitate from solution in bile.

Role of Bile Acids in Fat Digestion and Absorption

Bile acids are derivatives of cholesterol synthesized in the hepatocyte. Cholesterol, ingested as part of the diet or derived from hepatic synthesis is converted into the bile acids cholic and chenodeoxycholic acids, which are then conjugated to an amino acid (glycine or taurine) to yield the conjugated form that is actively secreted into cannaliculi.

Bile acids are amphipathic, that is, they contain both hydrophobic (lipid soluble) and polar (hydrophilic) regions. The cholesterol portion of a bile acid is hydrophobic and the amino acid conjugate is polar and hydrophilic.

Their amphipathic nature enables bile acids to carry out two important functions:

  • Emulsification      of lipid aggregates: Bile acids have detergent action on particles      of dietary fat which causes fat globules to break down or be emulsified      into minute, microscopic droplets. Emulsification is not digestion per se,      but is of importance because it greatly increases the surface area of fat,      making it available for digestion by lipases, which cannot access the      inside of lipid droplets.
  • Solubilization      and transport of lipids in an aqueous environment: Bile acids      are lipid carriers and are able to solubilize many lipids by forming micelles      – aggregates of lipids such as fatty acids, cholesterol and monoglycerides      – that remain suspended in water. Bile acids are also critical for      transport and absorption of the fat-soluble      vitamins.

Role of Bile Acids in Cholesterol Homeostasis

Hepatic synthesis of bile acids accounts for the majority of cholesterol breakdown in the body. In humans, roughly 500 mg of cholesterol are converted to bile acids and eliminated in bile every day. This route for elimination of excess cholesterol is probably important in all animals, but particularly in situations of massive cholesterol ingestion.

Interestingly, it has recently been demonstrated that bile acids participate in cholesterol metabolism by functioning as hormones that alter the transcription of the rate-limiting enzyme in cholesterol biosynthesis.

Enterohepatic Recirculation

Large amounts of bile acids are secreted into the intestine every day, but only relatively small quantities are lost from the body. This is because approximately 95% of the bile acids delivered to the duodenum are absorbed back into blood within the ileum.

Venous blood from the ileum goes straight into the portal vein, and hence through the sinusoids of the liver. Hepatocytes extract bile acids very efficiently from sinusoidal blood, and little escapes the healthy liver into systemic circulation. Bile acids are then transported across the hepatocytes to be resecreted into canaliculi. The net effect of this enterohepatic recirculation is that each bile salt molecule is reused about 20 times, often two or three times during a single digestive phase.

It should be noted that liver disease can dramatically alter this pattern of recirculation – for instance, sick hepatocytes have decreased ability to extract bile acids from portal blood and damage to the canalicular system can result in escape of bile acids into the systemic circulation. Assay of systemic levels of bile acids is used clinically as a sensitive indicator of hepatic disease.

Pattern and Control of Bile Secretion

The flow of bile is lowest during fasting, and a majority of that is diverted into the gallbladder for concentration. When chyme from an ingested meal enters the small intestine, acid and partially digested fats and proteins stimulate secretion of cholecystokinin and secretin. As discussed previously, these enteric hormones have important effects on pancreatic exocrine secretion. They are both also important for secretion and flow of bile:

  • Cholecystokinin: The name of this hormone      describes its effect on the biliary system – cholecysto = gallbladder and      kinin = movement. The most potent stimulus for release of cholecystokinin      is the presence of fat in the duodenum. Once released, it stimulates      contractions of the gallbladder and common bile duct, resulting in      delivery of bile into the gut.
  • Secretin: This hormone is secreted in      response to acid in the duodenum. Its effect on the biliary system is very      similar to what was seen in the pancreas – it simulates biliary duct cells      to secrete bicarbonate and water, which expands the volume of bile and      increases its flow out into the intestine.

The processes of gallbladder filling and emptying described here can be visualized using an imaging technique called scintography. This procedure is utilized as a diagnostic aid in certain types of hepatobiliary disease.



12 thoughts on “Preliminary Research

  1. Do we know what causes gallbladder cancer?

    Researchers have found several risk factors that make a person more likely to develop gallbladder cancer. (See the previous section, “What are the risk factors for gallbladder cancer?”) They are also beginning to understand how some of these risk factors may lead to gallbladder cancer.

    Most doctors studying the subject think that chronic inflammation is the major cause of gallbladder cancer. For example, when someone has gallstones, the gallbladder may release bile more slowly. This means that cells in the gallbladder are exposed to the chemicals in bile for longer than usual. This could lead to irritation and inflammation.

    In another example, abnormalities in the ducts that carry fluids from the gallbladder and pancreas to the small intestine can cause juices from the pancreas to flow backward (reflux) into the gallbladder and bile ducts. This reflux of pancreatic juices might inflame and stimulate growth of the cells lining the gallbladder and bile ducts. This might increase the risk of gallbladder cancer.

    Scientists have begun to understand how risk factors such as inflammation may lead to certain changes in the DNA of cells, making them grow abnormally and form cancers. DNA is the chemical in each of our cells that makes up our genes (the instructions for how our cells function). We usually look like our parents because they are the source of our DNA. However, DNA affects more than how we look.

    Some genes contain instructions for controlling when cells grow and divide. Genes that promote cell division are called oncogenes. Genes that slow down cell division or cause cells to die at the right time are called tumor suppressor genes. Cancers can be caused by DNA changes (mutations) that turn on oncogenes or turn off tumor suppressor genes. Changes in several different genes are usually needed for a cell to become cancerous.

    Some people inherit DNA mutations from their parents that greatly increase their risk for certain cancers. But inherited gene mutations are not thought to cause very many gallbladder cancers.

    Gene mutations related to gallbladder cancers are usually acquired during life rather than being inherited. For example, acquired changes in the TP53 tumor suppressor gene are found in many cases of gallbladder cancer. Other genes that may play a role in gallbladder cancers include KRAS, BRAF, CDKN2, and HER2.

    Many newer cancer drugs target cells with specific gene changes. Knowing which genes are abnormal in gallbladder cancer cells could help doctors determine which of these new drugs might be effective.


    Overweight, Rapid weight loss, Lack of exercise, Estrogen intake and birth control pills(estrogen increases the concentration of cholesterol in the bile), Chronic Heartburn, Over age 40 and increase in risk as one ages (Female especially those who have had children), Ethnicity (Pima Indians and Mexican-Americans), High triglycerides, high LDL cholesterol, decreased HDL cholesterol, Alcohol intake, Diet high in saturated fats, Diet high in refined foods and sugars

    The combination of a “civilized” diet, of saturated fats, fried foods, hydrogenated (or fake) fats and white sugar, white flour, highly-processed, nutrient-stripped food, along with a sedentary lifestyle tends to create an environment ripe for the formation of gallstones or other gallbladder problems.

    Eating too many of the wrong fats puts you at risk, but people who eat no fat at all are also at risk. No fat in the diet means that the gallbladder works less frequently, which could cause stasis and bile thickening. Moderate amounts of the right fats, such as olive oil, are much better.

    Although being female is an increased risk for gallbladder disease, according to a study published in BMC Gastroenterology 2002,(1) gallstones in children is on the rise. And men are not excepted either, although the ratio still tends to be 80% women to 20% men.

    Regardless of the diagnosis of your gallbladder disease, most of the symptoms will be similar. This is one of the reasons it is hard to know exactly what is going on without several tests. The most common symptoms are indigestion, gas, bloating, burping, belching, especially (but not necessarily) following a meal. It usually is a meal containing fat but after some time it seems to be unrelated not only to fat intake but even food intake. It may progress to constant tenderness or discomfort (unrelated to food intake) under the rib cage on the right side. The symptoms are similar to those of a gallbladder attack but with less severity. For a complete list of symptoms relating to gallbladder problems go to general gallbladder symptoms.

    Even if it does not seem to be connected to food now, if you can remember back, some symptoms of indigestion usually followed a meal. What caused or is causing the lack of fat digestion could be of various origin. A stone could be blocking the bile flow. The gallbladder could be distended due to stones or inflammation. There could be infection in the gallbladder causing tenderness or the tenderness could simply be due to stasis of bile causing distention. The gallbladder could be not emptying fully (biliary dyskinesia) and lack of bile causes improper fat digestion. Or the problem could start in the liver with stasis of bile there and the formation of sludge or tiny calculi slowing bile flow and causing it to thicken. Constipation and weight gain can also be symptoms of gallbladder problems.

    Bile Reflux, just as it sounds, is similar to acid reflux but in this case it is caused by the upward flow of bile from the duodenum of the small intestine into the stomach and the esophagus. The pyloric sphinter is a valve at the base of the stomach that opens to allow the passage of food into the small intestine. It is also supposed to keep food and bile acids from back flowing into the stomach. The symptoms of Bile Reflux are similar to the burning pain of heartburn but also may include nausea and vomiting of bile. Weight loss may also be an accompanying symptom. Treatment often includes antacids which are only partially helpful. The fact that antacids do not relieve symptoms is often diagnostic of bile reflux. Drugs that bind bile salts are generally more effective. Left untreated, bile reflux can cause gastritis, ulcers and possibly stomach cancer.

    Bile reflux can be caused by gallbladder surgery, but is more often a result of gastric surgery. The pyloric valve can also be obstructed by scar tissue or by an ulcer.

    Biliary Dyskinesia:
    Acalculous cholecystopathy which means disease or condition of the gallbladder without the presence of gallstones. You might also call it functional gallbladder disorder or impaired gallbladder emptying. Some causes may be chronic inflammation, stress, a problem with the smooth muscles of the gallbladder or the muscle of the Sphincter of Oddi being too tight. Also, research shows that hypothyroidism contributes to biliary dyskinesia.

    Symptoms – right upper quadrant pain in the absence of gallstones. Any gallbladder symptoms may accompany this problem as it results in lack of concentrated bile from the gallbladder to digest fats.
    If this is your diagnosis follow the thread to read about the connection between hypothyroid and gallbladder disease.

    Inflammation of the bile duct itself. Chole = bile and angi = duct. Acute cholangitis is usually caused by a bacterial infection resulting from stagnation of the bile in the duct. Choledocholithiasis, a gallstone that gets stuck or lodged in the bile duct can create an obstruction that results in an infection. Less frequently, infections can evolve due to a stricture or narrowing of the duct itself such as in Primary Sclerosing Cholangitis (see below) or may accompany a cancer. Something blocks the free flow of the bile causing a stagnant condition which allows the bacteria to take hold. Symptoms associated with cholangitis are pain, fever, chills, jaundice, or yellowing, abdominal pain

    Inflammation of the gallbladder. Acute cholecystitis is nearly always due to gallstones but may be due to infection (bacterial). It can also be due to chemical irritation. Chronic cholecystitis occurs with or without stones (acalculous cholecystitis is without). If there are no stones present the medical treatment used is often antispasmodics and/or laxatives. I use the products in the gallbladder attack kit for the pain in this case.

    Choledocholithias – Gallstones in the Bile Ducts
    This can be very painful and symptoms may differ depending upon where the stone is and if it is blocking bile flow. It can block the neck of the gallbladder causing distention and inflammation (cholecystitis). In the common bile duct it can cause a backing up of bile into the liver resulting in obstructive jaundice or into the pancreas causing acute pancreatitis.

    Cholelithiasis – Gallstones
    Solid crystalline precipitates in the BILIARY TRACT, usually formed in the GALLBLADDER. Gallstones, derived from the BILE, consist mainly of calcium, cholesterol, or bilirubin. Since the majority of symptoms relating to the gallbladder are caused by gallstones, there is a page dedicated that alone. If cholelithiasis or gallstones is your diagnosis, follow the thread from here to Gallstones.

    Symptoms – blocking of the secretion of bile results in the bile backing up into the circulation. This may result in jaundice and excess bilirubin in the blood which would make the urine dark and the stools pale or chalk colored. The excess of bile salts in the systemic circulation may cause intense itching and skin irritation. There may be fat in the stools and clotting time of blood may be impaired due to malabsorption of fats and Vitamin K which is a fat soluble vitamin that various clotting factors are dependent upon.

    Gallbladder Cancer
    The American Cancer Society estimates that about 8,750 people will be diagnosed with gallbladder cancer in 2006. Statistics show that it occurs 5x as often in Native American people in New Mexico than in whites. Women are more suseptible than men.

    There are rarely any symptoms with gallbladder cancer early on. In fact, it is often only discovered when the gallbladder is removed for other causes such as gallstones. Otherwise, gallbladder cancer is often quite advanced by the time it is diagnosed.

    If caught early, removing the gallbladder and affected tissues in bile ducts is the standard treatment.

  3. Found some stuff on how gall bladder diseases are caused, what symptoms are expected, how it can be prevented, etc. Hope this information will be useful for our report. If anyone can find some information on what kind of procedures are done once they find out they have gallbladder disease, or what kind of antibiotics they can take, or any information on how its treated, that will be great,

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