Digestive Functions of Liver & Pancreas PDF

Digestive Functions of Liver & Pancreas Learning Outcomes Explain the major functions of the liver on digestion. Explain the characteristics of the hepatic circulation between canalicular lumen and sinusoids. Explain blood flow properties with the related zone on the liver. Explain the bile acid syn...

Digestive Functions of Liver & Pancreas Learning Outcomes Explain the major functions of the liver on digestion. Explain the characteristics of the hepatic circulation between canalicular lumen and sinusoids. Explain blood flow properties with the related zone on the liver. Explain the bile acid synthesis and enterohepatic circulation of bile salts. Describe the hormonal and neural mechanisms that coordinate gallbladder emptying. Explain the role of the pancreas on digestion. Understand how and when the digestive enzymes of the pancreas become active. Explain the effects of CCK and secretin hormones on the sphincter of Oddi, on gallbladder secretions, and on gastric and duodenal motility. As chyme enters the duodenum (the first part of the small intestine) accessory organs—the pancreas, liver, and gallbladder—add their secretions. The pancreas and liver are accessory glandular organs that release exocrine secretions. Pancreas The pancreas is an organ that contains both types of secretory epithelium: endocrine and exocrine. Endocrine secretions come from clusters of cells called islets and include the hormones insulin and glucagon. Exocrine secretions include digestive enzymes and a watery solution of sodium bicarbonate, NaHCO3. Human Physiology: An Integrated Approach 8e Pearson 2019 The exocrine portion of the pancreas consists of lobules called acini. Ducts from the acini empty into the duodenum. The acinar cells secrete digestive enzymes, and the duct cells secrete the NaHCO3 solution. Medical Physiology: A Cellular and Molecular Approach 2e Enzyme Secretion Most pancreatic enzymes are secreted as zymogens (inactive enzyme precursors) that must be activated upon arrival in the intestine. This activation process is a cascade that begins when brush border enteropeptidase converts inactive trypsinogen to active trypsin. Trypsin then converts the other pancreatic zymogens to their active forms. The signals for pancreatic enzyme release include distension of the small intestine, the presence of food in the intestine, neural signals, and the GI hormone CCK. Pancreatic enzymes enter the intestine in a watery fluid that also contains bicarbonate. Human Physiology: An Integrated Approach 8e Pearson 2019 Protein digestion Trypsin, Chymotrypsin, Carboxypolypeptidase By far the most abundant of these is trypsin. Trypsin and chymotrypsin split whole and partially digested proteins into peptides of various sizes but do not cause the release of individual amino acids. However, carboxypolypeptidase splits some peptides into individual amino acids, thus completing the digestion of some proteins to the amino acid state. Carbohydrate digestion Pancreatic amylase, which hydrolyzes starches, glycogen, and most other carbohydrates (except cellulose) to form mostly disaccharides and a few trisaccharides Fat digestion Pancreatic lipase, which is capable of hydrolyzing neutral fat into fatty acids and monoglycerides, Cholesterol esterase, which causes hydrolysis of cholesterol esters, Phospholipase A2, which splits fatty acids from phospholipids. It is important that the proteolytic enzymes of the pancreatic juice not become activated until after they have been secreted into the intestine because the trypsin and the other enzymes would digest the pancreas. Fortunately, the same cells that secrete proteolytic enzymes into the acini of the pancreas simultaneously secrete another substance called trypsin inhibitor. This substance, which is formed in the cytoplasm of the glandular cells, prevents activation of trypsin inside the secretory cells and in the acini and ducts of the pancreas. In addition, because it is trypsin that activates the other pancreatic proteolytic enzymes, trypsin inhibitor prevents the activation of the other enzymes as well. Bicarbonate Secretion Bicarbonate secretion into the duodenum neutralizes acid entering from the stomach. A small amount of bicarbonate is secreted by duodenal cells, but most come from the pancreas. Bicarbonate production requires high levels of the enzyme carbonic anhydrase, levels similar to those found in renal tubule cells and red blood cells. Bicarbonate produced from CO2 and water is secreted by an apical Cl-- HCO3 exchanger. Hydrogen ions produced along with bicarbonate leave the cell on basolateral Na+-H+ exchangers. The chloride for bicarbonate exchange enters the cell on a basolateral NKCC cotransporter and leaves via an apical CFTR channel. Luminal Clthen reenters the cell in exchange for HCO3entering the lumen. Human Physiology: An Integrated Approach 8e Pearson 2019 Medical Physiology: A Cellular and Molecular Approach 2e Defects in CFTR channel structure or function cause the disease cystic fibrosis, and disruption of pancreatic secretion is one hallmark of cystic fibrosis. In cystic fibrosis, an inherited mutation causes the CFTR channel protein to be defective or absent. As a result, secretion of Cl- and fluid ceases but goblet cells continue to secrete mucus, resulting in thickened mucus. In the digestive system, the thick mucus clogs small pancreatic ducts and prevents digestive enzyme secretion into the intestine. Regulation of Pancreatic Secretion Basic Stimuli That Cause Pancreatic Secretion Three basic stimuli are important in causing pancreatic secretion: 1. Acetylcholine, which is released from the parasympathetic vagus nerve endings and other cholinergic nerves in the enteric nervous system 2. Cholecystokinin (CCK), which is secreted by the duodenal and upper jejunal mucosa when food enters the small intestine 3. Secretin, which is also secreted by the duodenal and jejunal mucosa when highly acidic food enters the small intestine Acetylcholine and CCK, stimulate the acinar cells of the pancreas, causing the production of large quantities of pancreatic digestive enzymes but relatively small quantities of water and electrolytes to go with the enzymes. Without the water, most of the enzymes remain temporarily stored in the acini and ducts until more fluid secretion comes along to wash them into the duodenum. Secretin, in contrast to the first two basic stimuli, stimulates the secretion of large quantities of water solution of sodium bicarbonate by the pancreatic ductal epithelium. Phases of Pancreatic Secretion 1. Cephalic phase (by smell, taste of food) 20-25% of max. secretion 2. Gastric phase (distension & gastrin) – 10-20% of max. secretion 3. Intestinal phase – 50-70% Parasympathetic fibers increase pancreatic secretions Two main hormones released from the small intestine regulate pancreatic secretions: I cells: Cholecystokinin (CCK) S cells: Secretin Phases of Pancreatic Secretion Pancreatic secretion, as with gastric secretion, occurs in three phases: the cephalic phase, the gastric phase, and the intestinal phase. Cephalic and Gastric Phases. During the cephalic phase of pancreatic secretion, the same nervous signals from the brain that cause secretion in the stomach also cause acetylcholine release by the vagal nerve endings in the pancreas. This signaling causes moderate amounts of enzymes to be secreted into the pancreatic acini, accounting for about 20%-25% of the total secretion of pancreatic enzymes after a meal. During the gastric phase, the presence of food in the stomach stimulates pancreatic secretions— primarily from the acinar cells—through two routes distention of the stomach activates a vagovagal reflex. protein digestion products (peptones) stimulate gastrin release from the stomach, which is a poor agonist of the CCKA receptors on acinar cells Medical Physiology: A Cellular and Molecular Approach 2e During the intestinal phase, chyme entering the proximal region of the small intestine stimulates a major pancreatic secretory response by three major mechanisms: Gastric acid entering the duodenum— and to a lesser extent, bile acids and lipids—stimulates duodenal S cells to release secretin, which stimulates duct cells to secrete HCO3- and fluid. A threshold duodenal pH of