Pancreatic and billary secretions Flashcards
Discuss relationships between structures of bile acids and their physiological function
Solubility: Bile acids have a hydrophobic (lipophilic) region consisting of a steroid nucleus and a hydrophilic (lipophobic) region consisting of a carboxyl group and hydroxyl groups. This amphipathic structure allows bile acids to solubilize and emulsify dietary fats, which enhances their digestion and absorption in the small intestine.
Bile flow: Bile acids are synthesized in the liver and transported to the small intestine via the bile duct. Their hydrophilic region helps to maintain the flow of bile through the bile duct, preventing the formation of gallstones and aiding in the excretion of waste products from the liver.
Interaction with membrane proteins: Bile acids can interact with membrane proteins, including transporters and receptors, in the small intestine. These interactions can modulate the transport of lipids and other nutrients across the intestinal epithelium, as well as regulate signaling pathways involved in nutrient absorption and metabolism.
Regulation of cholesterol metabolism: Bile acids can also regulate cholesterol metabolism by activating nuclear receptors such as farnesoid X receptor (FXR) and liver X receptor (LXR). These receptors are involved in the synthesis and transport of bile acids and cholesterol, as well as the regulation of glucose and lipid metabolism in the liver.
Delineate relationships between bile acids and cholesterol in man
Synthesis: Bile acids and cholesterol are both synthesized in the liver from acetyl-CoA. Bile acids are derived from cholesterol and are synthesized in the liver through a series of enzymatic reactions involving several key enzymes, such as cholesterol 7α-hydroxylase. This enzyme converts cholesterol into 7α-hydroxycholesterol, which is the precursor for bile acid synthesis.
Cholesterol elimination: Bile acids play a critical role in the elimination of cholesterol from the body. After being synthesized in the liver, bile acids are secreted into the small intestine, where they emulsify dietary fats and enhance their digestion and absorption. Bile acids also bind to cholesterol and other lipids, facilitating their excretion from the body via the feces.
Enterohepatic circulation: Bile acids and cholesterol are both involved in the enterohepatic circulation, a process in which they are recycled between the liver and the small intestine. After being secreted into the small intestine, bile acids are reabsorbed into the bloodstream and transported back to the liver, where they can be reused for the synthesis of new bile acids. Cholesterol is also reabsorbed from the small intestine and transported back to the liver, where it can be used for the synthesis of new bile acids or other lipids.
Regulation: Bile acids and cholesterol are both regulated by several key nuclear receptors, such as farnesoid X receptor (FXR) and liver X receptor (LXR). These receptors are involved in the regulation of bile acid synthesis, cholesterol metabolism, and lipid homeostasis in the liver.
Describe functions of bile acids in human intestine
Emulsification of dietary fats: Bile acids emulsify dietary fats, which enhances their digestion and absorption in the small intestine. Bile acids have a hydrophobic (lipophilic) region that interacts with dietary fats, breaking them down into smaller droplets and increasing their surface area for enzymatic digestion.
Facilitation of lipid absorption: Bile acids also facilitate the absorption of lipids, including fatty acids, monoglycerides, and fat-soluble vitamins, across the intestinal epithelium. This is because bile acids form micelles with these lipids, which enables them to be transported across the hydrophilic mucus layer and into the enterocyte.
Modulation of gut microbiota: Bile acids can also modulate the composition and function of the gut microbiota, which has important implications for human health. Bile acids can act as signaling molecules that interact with specific receptors on the surface of gut bacteria, regulating their growth and metabolism.
Regulation of intestinal motility: Bile acids can also modulate intestinal motility, or the movement of food through the gastrointestinal tract. This is because bile acids can activate receptors in the intestinal smooth muscle, causing it to contract and move food through the intestine.
Outline clinical consequences of bile acid deficiency
Malabsorption: Bile acid deficiency can lead to malabsorption of dietary fats and fat-soluble vitamins, such as vitamins A, D, E, and K. This is because bile acids play a critical role in the emulsification and absorption of these nutrients in the small intestine. Malabsorption can lead to deficiencies of these nutrients, which can have serious health consequences.
Steatorrhea: Steatorrhea is a condition in which excess fat is excreted in the stool, resulting in loose, oily stools that are difficult to flush. Bile acid deficiency can lead to steatorrhea because the impaired digestion and absorption of dietary fats leads to their excretion in the stool.
Cholestasis: Cholestasis is a condition in which the flow of bile from the liver is impaired, leading to the accumulation of bile in the liver and bloodstream. Bile acid deficiency can contribute to cholestasis because bile acids are necessary for the formation and flow of bile.
Increased risk of gallstones: Bile acid deficiency can increase the risk of gallstones, which are hardened deposits of cholesterol and other substances that form in the gallbladder. This is because bile acids play a critical role in the solubilization and excretion of cholesterol from the liver and gallbladder.
Vitamin deficiencies: Bile acid deficiency can also lead to deficiencies of fat-soluble vitamins, such as vitamins A, D, E, and K. These vitamins are necessary for many physiological processes, including bone health, immune function, and blood clotting.
Describe the transport of bilirubin in plasma and liver
Bilirubin production: Bilirubin is produced in the liver as a result of the breakdown of heme from hemoglobin in red blood cells. This process releases iron, which is recycled for use in new red blood cells.
Binding to albumin: Once produced, bilirubin is transported in the blood bound to albumin, a protein that acts as a carrier molecule. Albumin protects bilirubin from being toxic to the body’s tissues, and allows it to be transported to the liver for further processing.
Uptake by hepatocytes: In the liver, bilirubin is taken up by hepatocytes, the primary cells of the liver. This uptake is facilitated by a specific transporter protein located on the surface of the hepatocyte.
Conjugation: Once inside the hepatocyte, bilirubin is conjugated, or chemically modified, with a molecule called glucuronic acid. This process makes bilirubin more water-soluble and less toxic, allowing it to be excreted from the body more easily.
Secretion: After conjugation, bilirubin is secreted into the bile canaliculi, small channels between hepatocytes that transport bile out of the liver. Bilirubin is then transported through the bile ducts to the small intestine, where it is ultimately excreted from the body in feces.
