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Chapter 18 Lecture Outline See separate PowerPoint slides for all figures and tables pre-inserted into PowerPoint without notes. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. I. Introduction to the Digestive System A. Introduction 1. From food, humans must get basic organic molecules to make ATP, build tissues, and serve as cofactors and coenzymes. a. Digestion breaks polymers (carbohydrates, fats, and proteins) into monomer building blocks via hydrolysis reactions b. Absorption takes these monomers into the bloodstream to be used by the cells Digestion of food through hydrolysis reactions Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Carbohydrate O H H O H H + O HO Carbohydratedigesting enzymes H2O OH Maltose Disaccharide + Water + Water O H H O H H + HO OH HO Glucose OH Glucose + Monosaccharides Protein H H R O N C C H H O N C C H R OH + H2O ProteinH digesting enzyme H R O N C C OH + H + Water O N C C H Amino acid Lipid + Amino acid H O C17H35C H C17H35COO C H C17H35COO C H C R H Peptide (portion of protein molecule) C17H35COO H + 3H2O Triglyceridedigesting enzyme OH HO C H HO C H HO C H O C17H35C H H + OH O C17H35C OH H Fat + Water Fatty acids + Glycerol OH Introduction, cont 2. The digestive tract is open at both ends and is continuous with the environment a. Considered “outside” the body b. Materials that cannot be digested (cellulose) never actually “enter” the body. 3. One-way transport allows for specialization of function along the tract B. Digestive Tract Functions 1. Motility – movement of food through the tract a. Ingestion: taking food into the mouth b. ________: chewing and mixing food with saliva c. Deglutination: swallowing d. Peristalsis: wave-like, one-way movement through tract e. ____________: churning and mixing while moving forward Digestive Tract Functions, cont 2. Secretion a. ________: digestive enzymes, hydrochloric acid, mucus, water, and bicarbonate b. Endocrine: hormones to regulate digestion 3. Digestion - breaking food down into smaller units, both physically and chemically 4. __________ - passing broken-down food into blood or lymph Digestive Tract Functions, cont 5. Storage and elimination - temporary storage and subsequent elimination of undigested food molecules 6. Immune barrier a. Simple columnar epithelium with tight junctions prevents swallowed pathogens from entering body. b. Immune cells in connective tissue of the tract promote immune responses C. Digestive System Divisions 1. Gastrointestinal tract (GI tract, alimentary canal): ____ feet long, from mouth to anus Oral cavity Pharynx Esophagus Stomach Small intestines Large intestines Anus 2. Accessory organs: teeth, tongue, salivary glands, liver, gallbladder, pancreas Organs of the Digestive System Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Parotid gland Oral cavity Teeth Pharynx Tongue Submandibular gland Sublingual gland Esophagus Diaphragm Stomach Liver Common bile duct Gallbladder Pancreas Duodenum Ascending colon Small intestine Transverse colon Descending colon Sigmoid colon Cecum Rectum Appendix Anal canal Anus C. GI Tract Layers 1. Also called tunics 2. There are four tunics: a. Mucosa: inner secretory and absorptive layer; may be folded to increase surface area b. __________: very vascular, to pick up nutrients; also has some glands and nerve plexuses c. Muscularis: smooth muscle; responsible for peristalsis and segmentation; myenteric plexus for control by the ANS d. ________: outer binding and protective layer Layers of the Digestive Tract Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Artery Vein Mesentery Serosa Plica circularis Mucosa Submucosa Longitudinal muscle (a) Circular muscle Serosa Muscularis externa Outer longitudinal Myenteric plexus Inner circular Submucosal plexus Gland in submucosa Muscularis mucosae Lymph nodule Intestinal crypt (of Lieberkühn) Lamina propria Lacteal (b) Villi Epithelium E. Regulation of the GI Tract 1. Parasympathetic division (extrinsic regulation) a. Stimulates esophagus, stomach, small intestine, pancreas, gallbladder, and first part of large intestine via vagus nerve b. Spinal nerves in sacral region stimulate lower large intestine. c. Preganglionic neurons synapse on __________ and _________ plexuses. Regulation of the GI Tract, cont 2. Sympathetic division (extrinsic regulation) a. Inhibits peristalsis and secretion b. Stimulates contraction of sphincters 3. Hormones - from brain or other digestive organs Regulation of the GI Tract, cont 4. Intrinsic regulation a. Intrinsic sensory neurons in gut wall help in intrinsic regulation via separate enteric nervous system b. Paracrine signals II. From Mouth to Stomach A. Mouth 1. Mastication: Chewing breaks food down into smaller pieces for deglutition and mixes it with saliva. 2. Saliva: contains mucus, an antimicrobial agent, and salivary amylase to start digestion of starch. 3. Deglutition a. Involves coordinated contraction of 25 pairs of muscles b. Three parts: 1) Oral: voluntary; muscles of mouth and tongue mix food with saliva to form a bolus. 2) Pharyngeal: involuntary; initiated by receptors in the posterior oral cavity and oropharynx a) Uvula (soft palate) lifts to cover nasopharynx, and the epiglottis covers vocal cords. b) Upper esophageal sphincter relaxes. Deglutition, cont 3) __________: automatic; controlled by the swallowing center of brain stem; bolus is moved down esophagus to stomach via peristalsis Peristalsis in the esophagus Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Peristaltic wave Esophagus Bolus Stomach B. Esophagus 1. 2. 3. 4. About 10 inches long Passes through the diaphragm via the esophageal hiatus Lined with nonkeratinized stratified squamous epithelium Mouth, pharynx, and upper esophagus lined with skeletal muscles innervated by somatic motor neurons 5. Lower esophagus lined with smooth muscle controlled by autonomic nervous system 6. Lower esophageal sphincter opens to allow food to pass into stomach. It stays closed to prevent regurgitation. C. Stomach 1. Functions a. Stores food b. Churns food to mix with gastric secretions c. Begins protein digestion d. Kills bacteria in the food (acid) e. Moves food into small intestine in the form of chyme 2. Stomach Structure a. Regions 1) Food is delivered from the esophagus to the cardiac region. 2) Upper region = fundus 3) Lower region = body 4) Distal region = pyloric region; ends at pyloric sphincter b. Lining has folds called _______. Regions and Structure of the Stomach Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cardia Esophagus Fundus Adventitia Longitudinal muscle Pyloric sphincter Duodenum Body Circular muscle Pyloric antrum Oblique muscle Submucosa Pylorus Mucosa Gastric rugae Stomach Structure, cont c. Gastric pits at base of folds lead to gastric glands that contain several types of secretory cells: 1) Mucus neck cells secrete mucus to help protect stomach lining from acid. 2) ________ cells secrete HCl acid and intrinsic factor (helps small intestine absorb vitamin B12). 3) _____ (zygomatic) cells secrete pepsinogen, the inactive form of a protein digesting enzyme Stomach Structure, cont 4) Enterochromaffin-like (ECL) cells secrete histamine and serotonin (paracrine signals). 5) G cells secrete _______ (hormone). 6) D cells secrete somatostatin (hormone). 7) Also secretes the hormone ______ that signals the brain to regulate hunger Gastric Pits & Gastric Glands Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Gastric pits Gastric gland Mucous cell Mucosa Parietal cell Submucosa Chief cell (b) (a) D. Pepsin and HCl Secretion 1. Formation of HCl a. Primary active transport of H+ via H+/K+ATPase pumps b. Facilitated diffusion of Cl− coupled to downhill movement of bicarbonate c. Parietal cells secrete Cl- as well as H+ into gastric juice while secreting bicarbonate into the blood Secretion of gastric acid by parietal cells Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Lumen of stomach H+ Facilitative diffusion Cl– K+ Cl– K+ Primary active transport (ATPase carrier) Parietal cell H+ CO2 + H2O CA H+ H2CO3 HCO3– Cl– Secondary active transport HCO3– Cl– Blood capillaries 2. Stimulation of HCl Secretion a. Gastrin: made in G cells; carried to parietal cells in blood; Also stimulates ECL cells to make histamine b. Histamine: also stimulates parietal cells via H2 histamine receptors 1) Examples: Tagamet and Zantac block H2 receptors. c. Parasympathetic neurons and ACh: stimulate parietal and ECL cells 3. Functions of HCl a. Drops pH to 2 b. Ingested proteins are denatured (allows enzymes access). c. Pepsinogen is converted to active pepsin (digests proteins). d. Serves as the optimal pH for pepsin activity 4. Function of ______ – catalyzes the hydrolysis of peptide bonds in the ingested proteins Activation of pepsin Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Lumen of stomach Ingested protein Pepsinogen Pepsin HCI Short peptides Pepsin Gastric mucosa 5. Stomach Defenses a. Acid and pepsin could damage the stomach lining. b. Defenses that help prevent this: 1) Adherent layer of mucus with alkaline bicarbonate 2) Tight junctions between epithelial cells 3) Rapid epithelial mitosis that replaces epithelium every three days 6. Digestion and Absorption in the Stomach a. Proteins begin digestion in the stomach. b. Starches begin digestion in the _____, but salivary amylase is not active at pH 2, so this activity stops in the stomach. c. Alcohol and NSAIDs (aspirin) are the only common substances absorbed in the stomach (due to high lipid solubility). 7. Peptic Ulcers a. Peptic ulcers: erosions of the mucosa of the stomach or duodenum produce by HCl b. Helicobacter pylori: bacterium that reduces mucosal barriers to acid c. Treatment for ulcers combines K+/H+ pump inhibitors (Prilosec) and antibiotics. 8. Acute Gastritis a. Inflammation of the submucosa caused by acid b. Histamine released as part of the inflammatory response can stimulate more acid release. c. Prostaglandins are needed to stimulate protective alkaline mucus production. d. NSAIDs inhibit prostaglandin activity and can lead to gastritis. e. Tagamet and Zantac inhibit H2receptors. 9. Duodenal ulcers a. Protected by adherent layer of mucus with bicarbonate b. Bicarbonate secreted by Brunner’s glands c. Acidic chyme neutralized by bicarbonate from the pancreas d. Zollinger-Ellison syndrome – ulcers due to high amounts of gastrin produced by a tumor III. Small Intestine A. Small Intestine Structure 1. Starts at the pyloric sphincter and ends at the ileocecal valve 2. Three sections: a. ________ – first 10 inches b. ________ – middle 2/5 c. ______ – last 3/5 3. Mucosa and submucosa folded into plicae circulares; mucosa further folded into villi; and epithelial plasma membranes folded into microvilli; these greatly increase the surface area for absorption of nutrients Small Intestine Structure Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Plica circulares Villi Duodenum Ascending colon Stomach Jejunum Mucosa Submucosa Mesentery Ileum Cecum Muscularis externa Appendix Plica circulares Circular muscle (a) (b) Longitudinal muscle Serosa 4. Small Intestine Functions a. Complete digestion of carbohydrates, proteins, and fats b. Absorption of nutrients 1) Sugars, lipids, amino acids, calcium, and iron absorbed in duodenum and jejunum 2) Bile salts, vitamin B12, water, and electrolytes in ileum 3) Very rapid due to villi and microvilli B. Villi and Microvilli 1. Villi a. Columnar epithelium with goblet cells (mucus) b. Capillaries absorb monosaccharides and amino acids, and lacteals absorb fats. c. Intestinal crypts (Crypts of Lieberkuhn) with Paneth cells (secrete antibacterial molecules of lysozyme and defensin) and mitotic stem cells (divide by mitosis to replenish intestinal cells every 4 to 5 days) 2. __________ (brush border) – folding of the apical surface of each epithelial cell Structure of an intestinal villus Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Simple columnar epithelium Lacteal Villus Capillary network Goblet cells Intestinal crypt Lymph vessel Arteriole Venule C. Intestinal Enzymes 1. Called brush border enzymes 2. Not released into lumen, but stay attached to plasma membrane with active site exposed to chyme 3. Hydrolyze disaccharides, polypeptides and other substrates to simple nutrient molecules Location of Brush Border Enzymes Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Lumen of small intestine Enz Microvilli Epithelial cell of duodenum Brush Border Enzymes D. Intestinal Contractions and Motility 1. Peristalsis is weak. Movement of food is much slower due to pressure at pyloric end. 2. Segmentation is stronger and serves to mix the chyme. 3. Smooth muscle contractions occur automatically due to endogenous pacemaker activity a. Graded depolarizations called slow waves produced by pacemaker cells called interstitial cells of Cajal produce action potentials in muscle cells. Segmentation of the small intestine Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Intestinal Contractions/Motility, cont b. Depolarization from the interstitial cells of Cajal opens voltage-gated Ca2+ channels in muscle cells action potential and contraction. c. Stimulation travels short distances through gap junctions but must be regenerated in neighboring pacemaker regions. d. Produces contractions needed for segmentation Slow waves in the intestines Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Slow waves –28 mV –62 5 sec 4. Regulation of Contraction a. Autonomic nerves influence enteric nervous system to stimulate or inhibit cells of Cajal. b. Acetylcholine from parasympathetic system interacts with muscarinic ACh receptors to increase amplitude and duration of slow waves. Regulation of Contraction Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Structures Interstitial cells of Cajal Functions Production of slow waves Conduction of slow waves to smooth muscle Smooth muscle cells Autonomic axon Depolarization and opening of Ca2+ channels, production of action potentials Neural input to ICC and smooth muscle IV. Large Intestine A. Large Intestine Structure 1. Regions a. Through the ileocecal valve into the b. Cecum c. Ascending colon d. Transverse colon e. Descending colon f. Sigmoid colon g. Rectum h. Anal canal i. Anus The large intestine Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Transverse colon Ascending colon Ileocecal valve Cecum Appendix Rectum Descending colon Ileum Haustrum Sigmoid colon Anal canal Large intestine structure, cont 2. Mucosa – columnar epithelial cells with goblet cells, crypts, lymphatic nodules, but no villi 3. Outer surface forms pouches called haustra 4. Large Intestine Function a. Absorption of water, electrolytes, vitamin K, and some B vitamins b. Production of vitamin _______ vitamins via microbial organisms c. Storage of feces B. Intestinal Microbiota 1. Several hundred different species of bacteria live in the large intestine; also called microflora a. Some are commensal. The bacteria benefit, and we aren’t harmed or benefitted. b. Others are mutualistic. Both bacteria and us benefit. c. Bacteria are mostly anaerobic. d. An infant receives its initial colonization of bacteria from its mother during birth. 2. Benefits from Microbes a. Microbes make vitamin K and some B vitamins. b. They also make fatty acids from cellulose. Some of these are used for energy by large intestine epithelial cells. We can’t absorb the fatty acids, but they help absorb electrolytes such as sodium, calcium, bicarbonate, magnesium, and iron. c. They outcompete harmful species of bacteria. d. Disruption of normal microflora can lead to inflammatory bowel disease. 3. Protection from intestinal bacteria a. Mucus from goblet cells prevents contact with epithelial cells. b. Secretion of _______ by Paneth cells in the crypts. c. Secretion of IgA antibodies by plasma cells Intestinal Microbiota, cont 4. Normal intestinal microbiota helps maintain a healthy epithelial barrier, limits inflammation, and promotes repair of damaged epithelium. 5. Commensal bacteria promote production of regulatory T lymphocytes rather than killer T cells a. Intestinal dendritic cells are antigen-presenting cells to activate T cells. C. Fluid and electrolyte absorption 1. Most absorption occurs in small intestine, but some is left for large intestine. 2. Not all water is absorbed; about 200 ml is left per day to be excreted with feces. 3. Water is absorbed passively following an osmotic gradient set up by active Na+/K+pumps. a. ________ stimulates greater salt and water absorption here. 4. Some minor secretion of water occurs by osmosis. D. Defecation 1. As material passes to the rectum, pressure there increases, the internal anal sphincter relaxes, and the need to defecate rises. 2. The external anal sphincter controls defecation voluntarily. 3. During defecation, longitudinal rectal muscles contract to increase pressure as the anal sphincters relax. 4. Aided by contraction of abdominal and pelvic skeletal muscles – Valsalva’s maneuver V. Liver, Gallbladder, and Pancreas A. Liver 1. Structure a. Largest abdominal organ; immediately beneath the diaphragm, mostly on the right side b. Has amazing regenerative abilities due to mitosis of hepatocytes c. Composed of hepatocytes that form hepatic plates separated by capillaries called sinusoids 1) Capillaries have fenestrae with no diaphragm or basement membrane 2) Very permeable, allowing passage of blood proteins, fat, and cholesterol Structure, cont d. Kupffer cells are also in the sinusoids. e. Hepatic damage due to alcohol or viral hepatitis causes liver fibrosis that can lead to cirrhosis of the liver. Microscopic structure of the liver Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Hepatic sinusoids Central vein Hepatic plate Bile ductule Branch of hepatic portal vein Branch of hepatic artery Bile canaliculi Bile ductule Portal triad 2. Hepatic Portal System a. Products of digestion absorbed in intestines are delivered to the liver via the hepatic portal vein. b. Veins from the pancreas, gallbladder, stomach, omentum, and spleen also join with the hepatic portal vein. c. After circulating through liver capillaries, the blood leaves via the hepatic vein to join regular venous circulation Hepatic Portal System, cont d. _____________– a unique pattern of capillaries veins capillaries veins e. Total hepatic blood flow is about 25% of cardiac output; needed to maintain hepatic clearance. 3. Liver Lobules a. Hepatic plates are arranged as liver lobules with hepatic arteries, hepatic portal veins, and a central vein. b. Hepatic artery and hepatic portal vein open into the sinusoids between the plates c. Bile secreted by the hepatocytes is released into bile canaliculi, which drain into bile ducts, then to hepatic ducts away from the liver. Flow of blood and bile in a liver lobule Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Branch of portal vein Bile ductule Branch of hepatic artery Bile canaliculus Hepatic plate Sinusoids Central vein 4. Enterohepatic circulation a. Aside from bile, the liver secretes other substances into the bile ducts to clear them from the blood. b. Some of the molecules released into the bile are absorbed again in the small intestine and returned to the liver. c. These molecules are part of enterohepatic circulation; analogous to renal clearance. d. Eventually molecules are excreted in feces. Enterohepatic Circulation Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Liver Hepatic portal vein Gallbladder Small intestine Common bile duct Compounds excreted by the liver into bile B. Liver Functions 1. Bile production and secretion a. The liver makes __________ ml of bile per day. b. Bile is composed of: 1) Bile pigment (_______) 2) Bile salts 3) Phospholipids (lecithin) 4) ____________ 5) Inorganic ions c. Bilirubin 1) Produced in ______, liver, and bone marrow a) Derived from _____ (minus iron) from hemoglobin b) Not water-soluble 1) Carried attached to _______ in the blood 2) Not directly filtered by kidneys or secreted into bile 3) Some free bilirubin is conjugated with glucuronic acid to make it water- soluble Bilirubin, cont 2) Conjugated bilirubin is secreted into the bile, where it is taken to the small intestine. a) ________ there turn it into urobilinogen, which makes feces brown. b) 30−50% is absorbed by the intestines and taken back to the liver. c) Some is used to make bile, and some remains in blood to be filtered by the kidneys where it gives an amber color to the urine. Pathway for the metabolism of heme & bilirubin Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Red Blood Cells Hemolysis in spleen, liver, bone marrow Hemoglobin Heme Fe2+ Recycled to bone marrow Carbon monoxide (CO) Biliverdin NADPH NADP Bilirubin Hemoglobin Carboxyhemoglobin O2 Oxyhemoglobin Liver Carbon monoxide eliminated in exhaled breath Conjugated bilirubin (bilirubin glucuronide) Bilirubin eliminated in bile excreted in feces Enterohepatic circulation of urobilinogen Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. General circulation Kidney Vena cava Liver Hepatic portal vein Gallbladder Small intestine Common bile duct Urobilinogen in urine Bilirubin Bacteria Urobilinogen Urobilinogen in feces d. Bile Salts 1) Made from bile acids conjugated with glycine or taurine 2) Bile acids: derived from __________ a) Four polar groups on each molecule b) Cholic acid and chenodeoxycholic acid c) Most is recycled in enterohepatic circulation. d) ½ gram of cholesterol is broken down and lost in the feces through this pathway. Bile Salts, cont 3) Form ________ with polar groups toward water and nonpolar groups inward toward the fat a) Fats enter the micelle and are emulsified. b) Provides a greater surface area for fat digestion by lipase Bile acids form micelles Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. OH CH3 CH CH2 CH2 HO OH (a) Cholic acid (a bile acid) Nonpolar Polar (b) Simplified representation of bile acid (c) Micelle of bile acids COOH 2. Detoxification of Blood a. The liver can remove hormones, drugs, and other substances in three ways: 1) Excreted into _____ 2) Phagocytized by ________ lining sinusoids 3) Chemically altered by hepatocytes a) ________ is converted into urea, porphyrins into bilirubin, and purines into uric acid b) Urea is returned to the blood to be filtered by the kidneys. c) Steroids and xenobiotics are altered and then secreted into bile. 3. Secretion of Glucose, triglycerides, and ketone bodies a. The liver helps balance blood glucose levels by removing glucose and storing it as ________ (glycogenesis) and triglycerides (________) or by breaking down glycogen (glycogenolysis) and releasing it into the blood. b. The liver can also make glucose from amino acids (_____________) and convert fatty acids into ketones (ketogenesis). 4. Production of plasma proteins a. Plasma albumin and most plasma globulins, clotting factors and angiotensinogen are produced by the liver. b. Albumin provides colloid osmotic pressure and transport c. Globulins provide transport and blood clotting d. Clotting factors I, II, III, V, VII, IX, XI B. Gallbladder 1. Sac-like organ attached to the inferior surface of the liver 2. Stores and concentrates bile from the liver: Liver Bile ducts Hepatic duct Cystic duct Gallbladder Cystic duct Common bile duct Sphincter of Ampulla or Oddi into the duodenum Pancreatic juice and bile secretion into the duodenum Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Hepatic ducts Pancreatic acinus Cystic duct Common bile duct Gallbladder Pancreatic juice Pancreatic islet (of Langerhans) Pancreas Pancreatic duct Duodenal papilla Duodenum Gallstones Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. (a) (b) a: © Dr. Sheril Burton; b: © Martin/Custom Medical Stock Photo C. Pancreas 1. Has endocrine and exocrine functions a. Endocrine: Islets of Langerhans cells (Pancreatic Islets) make insulin and glucagon. b. Exocrine: Acinar cells make pancreatic juice, which is delivered to the duodenum via the pancreatic duct. Pancreas Structure Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Endocrine portion Pancreatic islet (of Langerhans) Zymogen granules Exocrine portion Acinar cells Pancreatic acini To pancreatic duct and duodenum (b) (a) a: © Ed Reschke Duct Acinus 2. Pancreatic Juice a. Made up of bicarbonate + 20 digestive enzymes b. Enzymes for all three classes of macromolecules c. Bicarbonate formation 1) Made by cells lining the ductules 2) Made from CO2 from the blood a) First, carbonic acid is made. b) This dissociates to form H+ and bicarbonate. c) The bicarbonate is secreted into pancreatic juice, and H+ goes back into the blood. d) Bicarbonate is countertransported with Cl−. 3) People with cystic fibrosis have trouble secreting bicarbonate because of defective chloride carriers, which can lead to destruction of the pancreas. Formation and Secretion of Bicarbonate Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Lumen Blood K+ HCO3– Na+ K+ ATP HCO3– CI– CI– K+ CI– Na+ Na+ HCO3– H2CO3 CO2 Na+ H+ H+ d. Pancreatic Enzymes 1) Most are inactive (zymogens) until they reach the small intestine. a) Enterokinase activates trypsinogen trypsin (to digest protein). b) Trypsin activates other enzymes. Activation of Pancreatic Enzymes Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Pancreatic juice Other inactive enzymes (zymogens) Active enzymes Trypsin En Microvilli Epithelial cell of duodenum VI. Regulation of the Digestive System A. Introduction 1. Neural and endocrine control mechanisms a. Modifies GI tract functioning b. Sight, smell, taste, or thought of food can stimulate salivation and gastric secretions to “prime” the digestive tract for food. c. Stimulation goes from brain to organ via vagus nerve; a conditioned reflex d. Short reflexes – do not involve the brain e. GI tract produces some hormones and is the target for action Effects of GI hormones B. Regulation of gastric function 1. Motility and secretion are somewhat automatic. a. Contractions are stimulated spontaneously by pacesetter cells in greater curvature of stomach (intrinsic regulation). b. Secretion of HCl and pepsinogen occurs when proteins enter the stomach. 1) Initiated and regulated by G cells (gastrin), D cells (somatostatin), and ECL cells (histamine) 2. Three phases of extrinsic gastric regulation a. Cephalic phase: control by brain via vagus nerves 1) Stimulates ECL (major response), chief cells, and parietal cells 2) Lasts for the first 30 minutes of a meal Three phases of extrinsic gastric regulation, cont b. Gastric phase: triggered by arrival of food into stomach 1) Gastric secretion is stimulated by stomach distension (amount of food that enters) and the chemical nature of the chyme. 2) Positive feedback occurs; as more proteins are broken down, more secretions are released to break them down (glucose has no effect and fat inhibits gastric secretion). Gastric phase, cont 3) There is also a negative-feedback system. As pH drops (due to more HCl), somatostatin is released. This inhibits gastrin secretion. 4) Large amounts of proteins and polypeptides buffer pH, so secretion matches protein concentration. Regulation of gastric secretion Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Gastric epithelium Amino acids Stomach lumen + Vagus nerve + Gastrin – G cell ECL cell Systemic circulation + + Histamine HCl + Parietal cell Three phases of extrinsic gastric regulation, cont c. ________________: inhibition of gastric activity when chyme enters the small intestine 1) Slows the movement of chyme into the duodenum to allow enough time for digestion and absorption 2) Stretch when food enters the duodenum stimulates a neural reflex that inhibits gastric stimulation via the vagus nerve. 3) The presence of fats stimulates the duodenum to make enterogastrone which inhibits gastric function. 4) Enterogastric hormones a) GIP – glucose-dependent insulinotropic peptide – stimulates insulin secretion and inhibits gastric function b) Somatostatin c) CCK – cholecystokinin – secreted by the duodenum in response to chyme d) GLP-1 – glucagon-like peptide-1 – secreted by the ileum – insulin stimulator Three Phases of Gastric Secretion C. Regulation of Intestinal Function 1. Enteric nervous system (ENS): neurons and glial cells that innervate the intestines a. Includes myenteric plexus and submucosal plexus b. Acts independently from CNS but with some feedback to CNS via vagus nerve (extrinsic afferents) c. Involved in regulation by the ANS d. Innervates interstitial cells of Cajal and smooth muscle to intrinsically regulate peristalsis Enteric Nervous System Coordinates Peristalsis Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 2. Motor neurons stimulate contraction behind bolus Excitation Smooth muscle + Interneurons activate motor neurons ACh Contraction Substance P ACh 1. Bolus of food stimulates sensory neurons Distention Interneurons activate motor neurons Mucosal stimulus Inhibition Bolus 2. Motor neurons produce relaxation in front of bolus Relaxation – Motor neurons Interneurons Sensory Lumen Mucosa and submucosa Circular muscle Longitudinal muscle 2. Paracrine Regulation a. Enterochromaffin-like cells in intestinal mucosa secrete serotonin and motilin in response to pressure (filling) and chemicals in the food. This stimulates muscle contractions. b. ________: made in ileum and colon; stimulates the secretion of water and Cl− and inhibits absorption of Na+. More water and salt are lost in feces. Acts by activating guanylate cyclase to produce second messenger cGMP 3. Intestinal reflexes a. Gastroileal reflex: increased gastric activity, increased ileum activity and movement of food through ileocecal valve b. ___________ reflex: distension of ileum causes a decrease in gastric motility c. Intestino-intestinal reflex: Over-distension of one portion of the intestine causes relaxation of other portions. D. Regulation of pancreatic juice and bile secretion 1. When chyme enters the duodenum, two hormones are produced: a. Secretin is produced in response to a drop in pH. (Production stops with a rise in pH.) b. Cholecystokinin (CCK) is produced in response to the presence of partially digested proteins and fats in chyme. (Production stops when food leaves small intestine.) 2. Secretion of Pancreatic Juice a. Pancreatic enzyme production of trypsin, lipase, and amylase is stimulated by ACh from vagus nerve, CCK, and secretin. 1) ACh and CCK use Ca2+ as a second messenger. 2) Secretin uses cAMP as a second messenger. b. Bicarbonate production is stimulated by secretin. 3. Secretion of Bile a. The liver produces bile continuously, but the arrival of food into the duodenum stimulates increased production of bile. b. Happens when: 1) Bile acids are returned to the liver after intestinal absorption via enterohepatic circulation. 2) Secretin and CCK stimulate increased bicarbonate secretion into bile. 3) CCK (in response to the presence of fat in chyme) stimulates gallbladder contraction. E. Trophic effects of GI hormones 1. GI hormones have a trophic effect for maintenance of their target organs 2. Structure of the gastric mucosa is dependent on gastrin 3. Structure of the acinar cells of the pancreas depends on CCK VII. Digestion and Absorption of Food A. Digestion & Absorption of Carbohydrates 1. Most carbohydrates are ingested as starch or sugars such as sucrose and lactose a. Starch digestion begins in mouth with salivary amylase; polysaccharides shorter chains b. No digestion in the stomach – too acidic c. Continues in intestines with pancreatic amylase; short chains disaccharides & maltriose d. Brush border enzymes finish breaking down disaccharides (maltose, sucrose, lactose) to simple sugars (mainly glucose) Action of pancreatic amylase Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Short oligosaccharide Glucose Amylase Maltriose Starch Maltose 2. Absorption of Carbohydrates a. Monosaccharides are absorbed across the epithelium via: 1) Secondary active transport with sodium (Clfollows) 2) Facilitated diffusion through GLUT carriers into interstitial fluid and then to capillary blood of the villus 3) Water follows the NaCl through a paracellular route and is absorbed with glucose and NaCl B. Digestion & Absorption of Proteins 1. Digestion of proteins a. Begins in ______ with pepsin and hydrochloric acid to produce short-chain polypeptides b. Finishes in duodenum and jejunum with pancreatic trypsin, chymotrypsin, elastase, and carboxypeptidase, and the brush border enzyme aminopeptidase. c. Final products are amino acids, some dipeptides and tripeptides 2. Absorption of Proteins a. Free amino acids cotransported with Na+ b. Dipeptides and tripeptides cross via secondary active transport using a H+ gradient. 1) Hydrolyzed into free amino acids within the cytoplasm of the epithelial cells c. Free amino acids move by facilitated diffusion into interstitial fluid, then to the blood capillaries of the villi Digestions & Absorption of Proteins Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Lumen Polypeptide chain Exopeptidase Endopeptidase Amino acids Brush border enzymes (microvilli) Tripeptidase Dipeptidase Epithelial cell Capillary blood C. Digestion & Absorption of Fats 1. Digestion of fats a. Fat digestion begins in ________ when bile emulsifies the fat and the pancreatic enzyme lipase, aided by colipase, breaks it down into fatty acids and glycerol b. Phospholipase A (from pancreas) digests phospholipids into fatty acids and lysolecithin. Digestion of Fats Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. H O H C O C O H C O C O H C O C Triglyceride H Glycerol Fatty acids Lipase + 2 HOH H H H C OH C O C OH O C + H Monoglyceride Free fatty acids Fat Emulsification and Digestion Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Step 1: Emulsification of fat droplets by bile salts From liver and gallbladder Step 2: Hydrolysis of triglycerides in emulsified fat droplets into fatty acid and monoglycerides Step 3: Dissolving of fatty acids and monoglycerides into micelles to produce “mixed micelles” Bile duct Micelles of bile salts, cholesterol, and lecithin 1 2 From stomach + Free fatty acids Lipase Monoglycerides Fat droplets (triglycerides) Emulsified fat droplets (triglycerides) 3 Into micelles 2. Absorption of Fats a. Fatty acids, monoglycerides, and lysolecithin move into bile ________ and are transported to brush border. b. The fat molecules then leave the micelles and diffuse into the epithelial cells of the villi. c. Inside the epithelial cells, they are regenerated into triglycerides, cholesterol, and phospholipids and combined with proteins to form ____________. d. Chylomicrons are secreted by exocytosis into the central lacteal of the villus Fat Absorption Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Mixed Micelles with Triglycerides Bile salts, lipase Fatty acids Lumen of small intestine Monoglycerides Fatty acids Monoglycerides Triglycerides + Protein Chylomicrons To thoracic duct Lacteal 3. Transport of Lipids in Blood a. The lymphatic system drops chylomicrons into the bloodstream at the thoracic duct. b. They pick up an apolipoprotein (ApoE), which allows them to bind to receptors on the capillary endothelium within muscles and adipose tissue. 1) Here they are digested by lipoprotein lipase, which releases free fatty acids for use by muscle cells or for storage by fat cells. 2) The remaining remnant particle containing cholesterol is released and travels in the blood to the liver. Transport of Lipids in Blood, cont c. Cholesterol and triglycerides made in the liver are combined with other apolipoproteins to form verylow-density lipoproteins (VLDLs) to deliver triglycerides to organs. d. Once triglycerides are removed, they are lowdensity lipoproteins (LDLs), which transport cholesterol to organs. e. Excess cholesterol is returned to the liver on highdensity lipids (HDL). Transport of Lipids in Blood f. HDL particles bind to receptors in the blood vessel walls and capture phospholipids and free cholesterol, reducing cholesterol amounts. g. Once the HDL is full, it travels to the liver and unloads the cholesterol. Lipid Carrier Proteins Characteristics of Major Digestive Enzymes