Role of Pancreas in Digestion PDF

Role of pancreas in digestion Oleg Osadchiy 1 Learning objectives ✓ Overview the structure and function of exocrine and endocrine portions of the pancreas. ✓ Explain the role of acinar and ductal cells in the process of secretion in the pancreatic glands. ✓ Describe the mechanism of bicarbonate secr...

Role of pancreas in digestion Oleg Osadchiy 1 Learning objectives ✓ Overview the structure and function of exocrine and endocrine portions of the pancreas. ✓ Explain the role of acinar and ductal cells in the process of secretion in the pancreatic glands. ✓ Describe the mechanism of bicarbonate secretion in pancreatic ductal cells. ✓ Compare and contrast the ionic composition of pancreatic juice and blood plasma at variable secretion rates. 2 Learning objectives ✓ Describe the types of pancreatic enzymes and their role in the process of digestion. ✓ Explain the role of neural and hormonal mechanisms in regulation of pancreatic secretion. ✓ Describe three phases of pancreatic secretion (cephalic, gastric, and intestinal). 3 Relation of pancreas to other abdominal organs. Pancreas includes exocrine portion and endocrine portion. Exocrine portion of pancreas ✓ Exocrine portion secretes pancreatic juice, which is released into the duodenum through the pancreatic duct. ✓ The pancreatic duct unites with the common bile duct from the liver and gallbladder to form a duct called the ampulla of Vater (or hepatopancreatic ampulla), which opens into the lumen of duodenum. ✓ Passage of pancreatic juice and bile through the ampulla of Vater into the duodenum is regulated by the sphincter of Oddi (made of smooth muscle). 6 Endocrine portion of pancreas ✓ Endocrine portion of pancreas consists of clusters of cells called the pancreatic islets (islets of Langerhans) that are scattered throghout the pancreatic tissue. ✓ These cells secrete four hormones – insulin, glucagon, somatostatin, and pancreatic polypeptide, which are released into the blood. 7 Pancreatic secretions are released through the pancreatic duct into the duodenum. Pancreatic gland. Pancreatic glands ✓ Pancreatic glands secrete pancreatic juice. ✓ Each pancreatic gland includes acinus and the ducts. ✓ Acinar cells secrete digestive enzymes, and the duct cells secrete bicarbonates. ✓ Pancreatic enzymes digest carbohydrates, fats, proteins, and nucleic acids. ✓ Bicarbonates neutralize hydrochloric acid entering small intestine from the stomach. 10 Primary pancreatic secretion formed in the acinus has ionic composition similar to blood plasma, and is isotonic. In the ducts, the pancreatic juice is enriched with bicarbonates. It remains isotonic. CA Mechanisms of bicarbonate secretion in the pancreatic ductal cell. Bicarbonate secretion in the pancreatic ducts ✓ Cells of the pancreatic duct take in CO2 from the blood, which is used to generate carbonic acid. ✓ Carbonic acid dissociates to bicarbonate and H+. ✓ Bicarbonate is secreted into the lumen of the duct by HCO3-/Cl- exchanger. ✓ Cl- delivered into the duct cell then passively leaks back through the CFTR chloride channel (cystic fibrosis transmembrane conductance regulator channel). ✓ H+ is removed from the cell by the Na+/H+ exchanger. 13 Pancreatic juice contains higher amounts of bicarbonate, but lower amounts of chloride, compared to blood plasma. Na+ and K+ concentrations are similar to blood plasma. Ionic composition of the pancreatic juice at variable flow rates ✓ With increasing secretion rate, the pancreatic juice contains more bicarbonate, and hence becomes more alkaline. ✓ With increasing secretion rate, Cl- concentration in the pancreatic juice is reduced, because bicarbonate is secreted into the lumen in exchange for delivery of Cl- into the ductal cells. ✓ Na+ and K+ concentrations in the pancreatic juice do not change upon variations in the rate of secretion. 15 Pancreatic juice ✓ Pancreatic glands are producing about 1 liter of pancreatic juice a day. ✓ It is rich with bicarbonate, and hence has an alkaline pH of 7.1-8.2. ✓ Alkaline pH buffers gastric acid in chyme that was evacuated to duodenum from stomach. ✓ This stops the action of pepsin, and creates appropriate pH for action of the digestive enzymes in the small intestine. 16 Amylase Effects of pH on activity of pepsin and pancreatic enzymes. Pancreatic enzymes (i) Protein-digesting enzymes – Trypsin, chymotrypsin, carboxypeptidase, aminopeptidase, elastase. (ii) Carbohydrate-digesting enzyme - Amylase. (iii) Triglyceride-digesting enzyme – Lipase, phospholipase A2, cholesterol ester hydrolase. (iv) Nucleic acid-digesting enzymes – Ribonuclease, deoxyribonuclease. 18 Proteases of the pancreatic juice are initially secreted in inactive form, and then activated in the intestinal lumen. Enterokinase Steps in activation of proteases of the pancreatic juice. Protein-digesting enzymes ✓ Protein-digesting enzymes of the pancreas are produced in inactive form, so they could not digest the pancreatic cells. ✓ Trypsin is secreted in inactive form called trypsinogen. ✓ Trypsinogen is converted to trypsin in the lumen of duodenum via effects of the intestinal enzyme enterokinase. ✓ Once trypsin is formed, it activates chymotripsinogen, procarboxypeptidase, proaminopeptidase, and proelastase, to produce active proteolytic enzymes. 21 Pancreatic protein-digesting enzymes (i) Endopeptidases (trypsin, chymotrypsin, elastase) (ii) Exopeptidases (capboxypeptidase and aminopeptidase). 22 Mechanism of action of endopeptidase. Mechanism of action of exopeptidase. Carboxypeptidase Aminopeptidase Action of pancreatic exopeptidases and endopeptidases. Pancreatic carbohydrate-digesting enzymes Amylase (secreted in active form) Splits starch into the oligosaccharides, trisaccharides, and disaccharides. 26 Pancreatic amylase digests starch. Pancreatic fat-digesting enzymes (i) Lipase (secreted in active form) - converts lipids to monoglycerids and free fatty acids. (ii) Cholesterol ester hydrolase (secreted in active form) – converts cholesterol ester to free cholesterol and fatty acids. (iii) Phospholipase A2 (secreted in inactive form. Activated by trypsin) – converts phospholipids to lysolecithin and fatty acids. 28 Fat-digesting enzymes of the pancreas. Bile assists to the action of pancreatic lipase by inducing fat emulsification. The role of colipase. Colipase ✓ One problem the enzyme lipase may encounter when digesting lipids is that it can be inactivated by bile salts. ✓ Lipase is absorbed on the surface of lipid droplet, but it is displaced by the binding of the bile acids to the exterior of the droplet. ✓ Colipase can bind to both bile acids and lipase, bringing lipase back to the surface of the lipid droplet (i.e., placing it in proximity of its substrate, which is triglycerides). ✓ Thus, colipase is acting as a cofactor for lipase. 32 Pancreatic nucleases (i) Ribonuclease (ii) Deoxyribonuclease These enzymes split RNA and DNA into mononucleotides. 33 Summary: Pancreatic enzymes (i) Protein-digesting enzymes – Trypsin, chymotrypsin, carboxypeptidase, aminopeptidase, elastase. (ii) Carbohydrate-digesting enzyme - Amylase. (iii) Triglyceride-digesting enzyme – Lipase, phospholipase A2, cholesterol ester hydrolase. (iv) Nucleic acid-digesting enzymes – Ribonuclease, deoxyribonuclease. 34 Regulation of pancreatic secretion (i) Hormonal regulation (secretin, CCK, and gastrin). (ii) Neural regulation (sympathetic and parasympathetic fibers of the ANS). 35 Hormonal regulation of pancreatic secretion Be mindful that pancreatic juice contains bicarbonates and enzymes, and their secretion is controlled in different ways. 36 Control of pancreatic secretion by secretin and CCK. Gastrin is released from G-cells in the stomach (antrum), and stimulates gastric acid secretion. Gastrin and CCK Gastrin stimulates secretion of enzymes in pancreatic acinar cells, acting via the same receptor as cholecystokinin. Neural regulation of pancreatic secretion 41 Sympathetic innervation of GIT (including pancreas). Parasympathetic innervation of GIT (including pancreas). Neural regulation of the pancreatic secretion ✓ Pancreatic glands are innervated by sympathetic and parasympathetic fibers of the ANS. ✓ Sympathetic fibers originate in the thoracic spinal cord, and switch to postganglionic neuron in the celiac and superior mesenteric plexuses. ✓ Parasympathetic fibers originate in vagal nuclei in medulla, and switch to postganglionic neuron in the enteric nervous system. ✓ Sympathetic fibers inhibit pancreatic secretion, whereas parasympathetic fibers stimulate it. 44 Vagus nerve stimulation increases a release of pancreatic enzymes similar to the effect of CCK. Phases of pancreatic secretion 46 Three phases of pancreatic secretion. The intestinal phase is most important, as it produces 80% of the total amount of pancreatic secretion induced by ingestion of a meal. Cephalic phase of the pancreatic secretion ✓ Thought of food, and its sight, smell and taste (during chewing) stimulate pancreatic secretion. ✓ Stimulation of pancreatic secretion is accounted for by the neural mechanism (vagus nerve). ✓ Vagal nuclei in the medulla receive signals from the cerebral cortex (about the thought of food, and its sight and smell), and from receptors of the mouth (about taste of food). ✓ Vagal nuclei then send a signal to pancreatic glands along the efferent vagal fibers, to release pancreatic enzymes. 48 Gastric phase of the pancreatic secretion ✓ When after swallowing the food is entering stomach, it produces mechanical and chemical stimulation of the gastric mucosa, which stimulates pancreatic secretion. ✓ Stimulation of the pancreatic secretion is accounted for by neural and hormonal mechanisms. ✓ Neural mechanism is related to vagal stimulation in response to the stretch of the stomach by food. ✓ Hormonal mechanism is related to gastrin release from the pyloric G-cells caused by proteins in the food. ✓ Both mechanisms increase the release of enzymes in the acinus of the pancreatic gland. 49 Intestinal phase of the pancreatic secretion ✓ When the gastric content is propelled to the duodenum, it produces mechanical and chemical stimulation of the duodenal mucosa, which stimulates pancreatic secretion. ✓ Stimulation of the pancreatic secretion is accounted for by neural and hormonal mechanisms. ✓ Neural mechanism is related to vagal stimulation in response to the stretch of the duodenum by chyme. ✓ Hormonal mechanism is related to the release of secretin and CCK from endocrine cells of the duodenum. ✓ Vagal stimulation and CCK increase the release of enzymes, and secretin stimulates the secretion of bicarbonates, in the pancreatic glands. 50 After this lecture, you are able to ✓ Explain the role of acinar and ductal cells within the pancreas in the secretion of pancreatic juice. ✓ Compare and contrast the ionic composition of pancreatic juice and blood plasma. ✓ Explain the role of pancreatic enzymes in digestion. ✓ Explain the neural and hormonal regulation of pancreatic secretion. ✓ Describe three phases of pancreatic secretion (cephalic, gastric, and intestinal). 51