Which of the following intestinal hormones stimulates the release of bile from the gall bladder?

Bile is a physiological aqueous solution produced and secreted by the liver. It consists mainly of bile salts, phospholipids, cholesterol, conjugated bilirubin, electrolytes, and water . Bile travels through the liver in a series of ducts, eventually exiting through the common hepatic duct. Bile flows through this duct into the gallbladder, where it is concentrated and stored. When stimulated by the hormone cholecystokinin (CCK), the gallbladder contracts, pushing bile through the cystic duct and into the common bile duct. Simultaneously, the sphincter of Oddi relaxes, permitting bile to enter the duodenal lumen. The hormone secretin also plays an important role in the flow of bile into the small intestine. By stimulating biliary and pancreatic ductular cells to secrete bicarbonate and water in response to the presence of acid in the duodenum, secretin effectively expands the volume of bile entering the duodenum. In the small intestine, bile acids facilitate lipid digestion and absorption. Only approximately 5% of these bile acids are eventually excreted. The majority of bile acids are efficiently reabsorbed from the ileum, secreted into the portal venous system, and returned to the liver in a process known as enterohepatic recirculation .



Bile is produced by hepatocytes and it is then modified by the cholangiocytes lining the bile ducts. The production and secretion of bile require active transport systems within hepatocytes and cholangiocytes in addition to a structurally and functionally intact biliary tree. Initially, hepatocytes produce bile by secreting conjugated bilirubin, bile salts, cholesterol, phospholipids, proteins, ions, and water into their canaliculi (thin tubules between adjacent hepatocytes that eventually join to form bile ducts) . The canalicular membrane of the hepatocyte is the main bile secretory apparatus that contains the intracellular organelles, the cytoskeleton of the hepatocyte, and carrier proteins. The carrier proteins in the canalicular membrane transport bile acid and ions. Transporter proteins found within the canalicular membrane use energy to secrete molecules into bile against concentration gradients. Through this active transport, osmotic and electrochemical gradients are formed. When conjugated bile salts enter the canaliculus, water follows by osmosis. The electrochemical gradient allows for the passive diffusion of inorganic ions such as sodium. The most significant promoter of bile formation is the passage of conjugated bile salts into the biliary canaliculus. The total bile flow in a day is approximately 600 ml, of which 75% is derived from hepatocytes, and 25% is from cholangiocytes. Approximately half of the hepatocyte component of bile flow (about 225 ml per day) is bile salt-dependent, and the remaining half bile salt independent. Osmotically active solutes such as glutathione and bicarbonate promote bile salt independent bile flow .

Canaliculi empty bile into ductules or cholangioles or canals of Hering. The ductules connect with interlobular bile ducts, which are accompanied by branches of the portal vein and hepatic artery forming portal triads. Bile is subsequently modified by ductular epithelial cells as it passes through the biliary tree. These cells, known as cholangiocytes, dilute, and alkalinize the bile through hormone-regulated absorptive and secretory processes. The cholangiocytes have receptors that modulate the bicarbonate-rich ductular bile flow, which is regulated by hormones. These receptors include receptors for secretin, somatostatin, cystic fibrosis transmembrane conductance regulator (CFTR), and chloride-bicarbonate exchanger. For example, when secretin stimulates receptors in the cholangiocyte, a cascade is initiated, which activates the CFTR chloride channel and allows the exchange of bicarbonate for chloride. In contrast, somatostatin inhibits the cAMP synthesis within the cholangiocytes, causing the opposite effect. While bombesin, vasoactive intestinal polypeptide, acetylcholine, and secretin enhance bile flow, somatostatin, gastrin, insulin, and endothelin inhibit the flow .

Bile Acids

Cholesterol catabolism by hepatocytes results in the synthesis of the two major primary bile acids, cholic acid and chenodeoxycholic acid. This process involves multiple steps, with cholesterol 7alpha-hydroxylase acting as the rate-limiting enzyme. Primary bile acids undergo dehydroxylation by bacteria in the small intestine, forming the secondary bile acids deoxycholic acid and lithocholic acid, respectively. Both primary and secondary bile acids are conjugated by the liver with an amino acid, either glycine or taurine. Conjugated bile acids are known as bile salts. Bile salts inhibit cholesterol 7alpha-hydroxylase, decreasing the synthesis of bile acids. Despite the increased water solubility of bile salts, they are amphipathic molecules overall . This critical property allows them to effectively emulsify lipids and form micelles with the products of lipid digestion. The bile acid pool is maintained mainly via the enterohepatic circulation and, to a small extent (about 5%), by the hepatic synthesis of bile acids, as long as the daily fecal loss of bile acids do not exceed 20% of the pool.

Cholecystokinin (CCK) is a hormone secreted by the I-cells of the upper small intestine in response to fat, protein, and some nonnutrients, for example, camostat, and a peptide/neurotransmitter secreted by neurons of the central and peripheral nervous systems.

From: Progress in Molecular Biology and Translational Science, 2013

The response to food begins even before food enters the mouth. The first phase of ingestion, called the cephalic phas, is controlled by the neural response to the stimulus provided by food. All aspects—such as sight, sense, and smell—trigger the neural responses resulting in salivation and secretion of gastric juices. The gastric and salivary secretion in the cephalic phase can also take place due to the thought of food. Right now, if you think about a piece of chocolate or a crispy potato chip, the increase in salivation is a cephalic phase response to the thought. The central nervous system prepares the stomach to receive food.

The gastric phase begins once the food arrives in the stomach. It builds on the stimulation provided during the cephalic phase. Gastric acids and enzymes process the ingested materials. The gastric phase is stimulated by (1) distension of the stomach, (2) a decrease in the pH of the gastric contents, and (3) the presence of undigested material. This phase consists of local, hormonal, and neural responses. These responses stimulate secretions and powerful contractions.

The intestinal phase begins when chyme enters the small intestine triggering digestive secretions. This phase controls the rate of gastric emptying. In addition to gastrin emptying, when chyme enters the small intestine, it triggers other hormonal and neural events that coordinate the activities of the intestinal tract, pancreas, liver, and gallbladder.

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Before we go into the digestive details of the small intestine, it is important that you have a basic understanding of the anatomy and physiology of the following digestion accessory organs: pancreas, liver, and gallbladder. Digestion accessory organs assist in digestion, but are not part of the gastrointestinal tract. How are these organs involved?

Upon entering the duodenum, the chyme causes the release of two hormones from the small intestine: secretin and cholecystokinin (CCK, previously known as pancreozymin) in response to acid and fat, respectively. These hormones have multiple effects on different tissues. In the pancreas, secretin stimulates the secretion of bicarbonate (HCO3), while CCK stimulates the secretion of digestive enzymes. The bicarbonate and digestive enzymes released together are collectively known as pancreatic juice, which travels to the small intestine, as shown below.

Which of the following intestinal hormones stimulates the release of bile from the gall bladder?

Figure 3.411 The hormones secretin and CCK stimulate the pancreas to secrete pancreatic juice1

In addition, CCK also stimulates the contraction of the gallbladder causing the secretion of bile into the duodenum.


The pancreas is found behind the stomach and has two different portions. It has an endocrine (hormone-producing) portion that contains alpha and beta cells that secrete the hormones glucagon and insulin, respectively. However, the vast majority of the pancreas is made up of acini, or acinar cells, that are responsible for producing pancreatic juice. The following video does a nice job of showing and explaining the function of the different pancreatic cells.

Video: The Pancreas (First 53 seconds)

Bicarbonate is a base (high pH) meaning that it can help neutralize acid. You can find sodium bicarbonate (NaHCO3, baking soda) on the ruler below to get an idea of its pH.

Which of the following intestinal hormones stimulates the release of bile from the gall bladder?

Figure 3.412 pH of some common items2

The main digestive enzymes in pancreatic juice are listed in the table below. Their function will be discussed further in later subsections.

Table 3.411 Enzymes in pancreatic juice

Pancreatic alpha-amylase
Pancreatic Lipase & Procolipase*
Phospholipase A2
Cholesterol Esterase

*Not an enzyme


The liver is the largest internal and most metabolically active organ in the body. The figure below shows the liver and the accessory organs position relative to the stomach.

Which of the following intestinal hormones stimulates the release of bile from the gall bladder?

Figure 3.413 Location of digestion accessory organs relative to the stomach3

The liver is made up two major types of cells. The primary liver cells are hepatocytes, which carry out most of the liver’s functions. Hepatic is another term for liver. For example, if you are going to refer to liver concentrations of a certain nutrient, these are often reported as hepatic concentrations. The other major cell type is the hepatic stellate (also known as Ito) cells. These are fat storing cells in the liver. These two cell types are depicted below.

Which of the following intestinal hormones stimulates the release of bile from the gall bladder?

Figure 3.414 Hepatocytes (PC) and hepatic stellate cells (HSC) along with an electron microscope image showing the lipid droplets within a stellate cell4

The liver’s major role in digestion is to produce bile. This is a greenish-yellow fluid that is composed primarily of bile acids, but also contains cholesterol, phospholipids, and the pigments bilirubin and biliverdin. Bile acids are synthesized from cholesterol. The two primary bile acids are chenodeoxycholic acid and cholic acid. In the same way that fatty acids are found in the form of salts, these bile acids can also be found as salts. These salts have an (-ate) ending, as shown below.

Which of the following intestinal hormones stimulates the release of bile from the gall bladder?

Figure 3.415 Structures of the 2 primary bile acids

Bile acids, much like phospholipids, have a hydrophobic and hydrophilic end. This makes them excellent emulsifiers that are instrumental in fat digestion. Bile is then transported to the gallbladder.


The gallbladder is a small, sac-like organ found just off the liver (see figures above). Its primary function is to store and concentrate bile made by the liver. The bile is then transported to the duodenum through the common bile duct.

Why do we need bile?

Bile is important because fat is hydrophobic and the environment in the lumen of the small intestine is watery. In addition, there is an unstirred water layer that fat must cross to reach the enterocytes in order to be absorbed.

Which of the following intestinal hormones stimulates the release of bile from the gall bladder?

Figure 3.416 Fat is not happy alone in the watery environment of the small intestine.

Here triglycerides form large triglyceride droplets to keep the interaction with the watery environment to a minimum. This is inefficient for digestion, because enzymes cannot access the interior of the droplet. Bile acts as an emulsifier, or detergent. It, along with phospholipids, forms smaller triglyceride droplets that increase the surface area that is accessible for triglyceride digestion enzymes, as shown below.

Which of the following intestinal hormones stimulates the release of bile from the gall bladder?

Figure 3.417 Bile acids and phospholipids facilitate the production of smaller triglyceride droplets.

Secretin and CCK also control the production and secretion of bile. Secretin stimulates the flow of bile from the liver to the gallbladder. CCK stimulates the gallbladder to contract, causing bile to be secreted into the duodenum, as shown below.

Which of the following intestinal hormones stimulates the release of bile from the gall bladder?

Figure 3.418 Secretion stimulates bile flow from liver; CCK stimulates the gallbladder to contract3

1. Don Bliss, NCI, http://visualsonline.cancer.gov

2. http://upload.wikimedia.org/wikipedia/commons/4/46/PH_scale.png

3. http://www.wpclipart.com/medical/anatomy/digestive/Digestive_system_diagram_page.png.html

4. http://www.comparative-hepatology.com/content/6/1/7


The Pancreas – http://www.youtube.com/watch?v=j5WF8wUFNkI