THE DIGESTIVE SYSTEM: Small Intestine and Pancreas Dalay Olson Ph.D Office: Jackson Hall 3-120 Email: [email protected] MAJOR JOBS OF THE SMALL INTESTINE Absorption Movement of nutrients from SI into the Secretions blood. Digestion Motility Macromolecule breakdown Secretions Enzymes required! Secretions Bicarbonate Digestive enzymes CCK and secretin Motility Mechanical mixing and forward Bloodstream (venous system) movement LEARNING OBJECTIVES 1 2 3 Review the layers of the SI wall Compare and contrast the intrinsic, Discuss the exocrine functions of the including the microstructure of the extrinsic and endocrine mechanisms pancreas and the regulation of these functions by Secretin and CCK. villus. of within the SI. Include initial stimuli and the intestinal response. SNA and PSNA 4 5 Describe how pancreatic secretions, bile Compare and contrast the absorption of and finally luminal surface enzymes carbohydrates, proteins and fats from the (brush border enzymes) digest lumen of the GI tract to the blood/lymph carbohydrates, proteins and fats. vessels. + THE PROBLEM WITH CHYME… THE PROBLEM WITH CHYME… H+ H+ H+ H+ H+ H+ H+ H+ Acidic WHY IS IT IMPORTANT TO NEUTRALIZE THE CHYME? Substrate Active site Mucosal protection Enzyme function Micelle formation ACIDIC CHYME: NEUTRALIZATION Sensor Enteroendocrine cells sense both acidity and chemical makeup of chyme. Enteroendocrine Response Enteroendocrine cells secrete carbohydrate rich mucus helps protect the mucosa from gastric acid Cell Enteroendocrine cells release Secretin into the bloodstream. Secretin signals the release of bicarbonate from the pancreatic duct into the intestine. BICARBONATE SECRETION Response Enteroendocrine cells release Secretin, a hormone, into the bloodstream. Secretin goes to the pancreas and signals the release of bicarbonate from the pancreatic duct into the intestine. Bicarbonate in the duodenum helps to neutralize the incoming chyme, preventing Bicarbonate epithelial damage. Secretin in the blood can also inhibit gastric motility in the stomach. Secretin Secretin Bloodstream Notice… 1. The blood moving H+ H+ through the duodenum becomes acidic due to increased H+ entering the blood. CO2 Moves out - secretin 2. HCO3 move into the into the SI to duct through a help neutralize HCO3-/Cl- exchanger the chyme BICARBONATE SECRETION Response Enteroendocrine cells release Secretin, a hormone, into the bloodstream. Secretin goes to the pancreas and signals the release of bicarbonate from the pancreatic duct into the intestine. Bicarbonate in the duodenum helps to neutralize the incoming chyme, preventing Bicarbonate epithelial damage. Secretin in the blood can also inhibit gastric motility in the stomach. Secretin Secretin Bloodstream Movement PERISTALSIS SEGMENTATION Two major types of movement in the gut REGULATORS OF MOTILITY Extrinsic Intrinsic Spontaneous EXTRINSIC REGULATORS OF THE SMALL INTESTINE Parasympathetic Sympathetic (Vagus) NE Ach NE Small Intestine NE Ach Ach Cholinergic Fibers (Ach) stimulate Sympathetic nerves (NE) inhibit digestive activity. digestive activity • Activating smooth muscle cell • Inhibiting smooth muscle cell contraction by increasing contraction by decreasing Ca2+ entry intracellular Ca2+. into smooth muscle cell. Overall forward movement and • Increasing rate of pacemaker firing. • Decreasing rate of pacemaker firing. mechanical breakup of the chyme PERISTALTIC WAVES IN THE SMALL INTESTINE Contraction in the intestine 1. A slow wave must reach threshold 1. The depolarization from the AP spreads through the intestine (gap junctions) depolarizing smooth muscle cells. 2. Depolarization is sensed by voltage gated Ca2+ channels causing them to open. 3. Ca2+ enters the smooth muscle cells and initiates muscle contraction. 4. The more Ca2+ present, the stronger the contraction. PERISTALTIC WAVES IN THE SMALL INTESTINE Pacemaker cells in the stomach generate a spontaneous, rhythmic depolarization known as a basic electrical rhythm (BER) that results in contraction of the longitudinal muscle. The pacemaker cells are influenced by outside mediators. Increased PSNA shifts the resting membrane potential towards threshold→ increased number of action potentials. Increased SNA shifts the resting membrane potential away from threshold→ decreasing number of action potentials. MIGRATING MOTOR COMPLEX (SPONTANEOUS) Motilin – Hormone that is released from mucosal cells in response to fasting (circulates in the blood). –Stimulates the Migrating Motor Complex –Increases intestinal peristalsis INTRINSIC REGULATORS OF THE SMALL INTESTINE Inter- neuron Myenteric or submucosal plexus Enteric Nervous System (ENS) – Can serve as a control center for local reflexes –Stretch activates sensory nerves that increase motility through activation of the enteric nervous system. + Digestion DIGESTION: BREAKDOWN MACRONUTRIENTS FOR ABSORPTION Macronutrient Sensor Enteroendocrine cells sense chemical makeup of chyme. (Carbohydrates, peptides and fats) Enteroendocrine Response The presence of fats, peptides and carbs activates a chemoreceptor found on the Cell enteroendocrine cell. The cell responds by releasing CCK, a hormone, into the bloodstream. DIGESTION: BREAKDOWN MACRONUTRIENTS FOR ABSORPTION Response The presence of fats, peptides and carbs activates a chemoreceptor found on the enteroendocrine cell. The cell responds by releasing CCK, a hormone, into the bloodstream. CCK signals the release of digestive enzymes (see list on next slide) from the pancreas, and bile from the liver into the intestine. Bile breaks up the fat droplets allowing the Lipase digestive enzymes to digest and breakup the fats and amino acids in the preparation for absorption. CCK CCK CCK inhibits gastric motility. Bloodstream PANCREAS Digestive Enzymes (CCK) • Acinar cells secrete digestive zymogens (inactive enzymes) and enzymes • α-amylase, proteases, lipases, nucleases Bicarbonate (Secretin) • Duct cells secrete bicarbonate • Bicarbonate secretion neutralizes the incoming gastric acid • Stimuli for bicarbonate release is secretin. LIVER Bile • Fat emulsification • Drug and metabolite detox SECRETIONS: HORMONAL REGULATORS OF THE PANCREAS Cholecystokinin (CCK) • Released from enteroendocrine cells in response to fats, peptides and carbs present in chyme. • Acts on the acinar cells in the pancreas to secrete digestive enzymes. • Acts on the gallbladder to initiate contraction and bile release. • Acts on the stomach to inhibit motility. Secretin • Released from enteroendocrine cells in response to acid in SI. • Acts on the duct cells to release bicarbonate. • Acts on the stomach to inhibit motility. Somatostatin (released from pancreas too!) • Released in response to elevated levels of CCK and secretin • Inhibits the release of CCK and Secretin (negative feedback). SOMATOSTATIN RECAP Stimulus for its release? • Increased acid in the stomach stimulates release of somatostatin from the stomach. • Increased plasma CCK and Secretin stimulates pancreatic release of somatostatin. Where does it come from? • Released from D-cells present in BOTH the stomach and pancreas! How does it act in the body? • Endocrine hormone that circulates in the blood What does it do? • Acts on the stomach to inhibit acid release. • Acts on the enteroendocrine cell to inhibit release of CCK and Secretin. NERVOUS SYSTEM REGULATORS OF THE PANCREAS Sympathetic Parasympathetic (Vagus) NE Ach NE NE Ach Ach Sympathetic nerves (NE) inhibit Cholinergic Fibers (Ach) secretion of alkaline juices and enhance rate of secretion of digestive enzymes from the alkaline juices and digestive pancreas. enzymes from the pancreas. Pancreas secretes digestive enzymes and alkaline juices (bicarbonate) that aid in digestion + Absorption Gus’ Balanced Meal • Carbohydrates • Fats • Protein CARBOHYDRATE DIGESTION CARBOHYDRATE ABSORPTION PROTEIN DIGESTION Brush border enzymes PROTEIN ABSORPTION Brush border enzymes FAT DIGESTION FAT ABSORPTION ELECTROLYTE & WATER ABSORPTION LEARNING OBJECTIVES 1 2 3 Review the layers of the SI wall Compare and contrast the intrinsic, Discuss the exocrine functions of the including the microstructure of the extrinsic and endocrine mechanisms pancreas and the regulation of these functions by Secretin and CCK. villus. of within the SI. Include initial stimuli and the intestinal response. SNA and PSNA 4 5 Describe how pancreatic secretions, bile Compare and contrast the absorption of and finally luminal surface enzymes carbohydrates, proteins and fats from the (brush border enzymes) digest lumen of the GI tract to the blood/lymph carbohydrates, proteins and fats. vessels. +.