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Digestive Physiology Overview • Inside gastrointestinal (GI) tract, food is broken down by hydrolysis reactions into molecular monomers • Most digestion of nutrients and absorption of monomers occurs in small intestine (90%) 18-3 Functions of the Digestive System – – – – Ingestion--taking food into mouth Mastication--chewing food and mixing it with saliva Deglutition--swallowing food Peristalsis--rhythmic wave-like contractions that move food through GI tract – Digestion– mechanical and chemical breakdown of food – Absorption--Is passage of digested end products into blood or lymph – Storage and Elimination--Includes temporary storage and subsequent elimination of indigestible components of food 18-6 Functions of Digestive System • Secretion: – Includes release of exocrine and endocrine products into GI tract – Exocrine secretions include: HCl, H2O, HCO3-, bile, lipase, pepsin, amylase, trypsin, elastase, and histamine – Endocrine includes hormones secreted into stomach and small intestine to help regulate GI system • e.g. gastrin, secretin, cholescytokinin, gastric inhibitory peptide, and somatostatin 18-7 Digestive System • Is composed of GI tract (alimentary canal) and accessory digestive organs • Organs include oral cavity, pharynx, esophagus, stomach, small and large intestine • Accessory organs include teeth, tongue, salivary glands, liver, gallbladder, and pancreas Regulation of GI Tract • Parasympathetic effects, arising from vagus and spinal nerves, stimulate motility and secretions of GI tract • Sympathetic activity reduces peristalsis and secretory activity • GI tract contains an intrinsic system that controls its peristaltic movements--the enteric nervous system • GI motility is also influenced by paracrine and hormonal signals 18-18 From Mouth to Stomach continued • Peristalsis propels food thru esophagus and GI tract – = wave-like muscular contractions – After food passes into stomach, the lower esophageal sphincter constricts, preventing reflux 18-23 Stomach • Is most distensible part of GI tract • Empties into the duodenum • Functions in: – storage of food; – initial chemical digestion of proteins – some mechanical digestion of all nutrients – kills bacteria with high acidity (HCl) – moves soupy food mixture (chyme) into intestine 18-25 Stomach • Gastric mucosa has gastric pits in its folds • Cells that line folds deeper in the mucosa, are exocrine gastric glands 18-28 Stomach continued • Gastric glands contain cells that secrete different products that form gastric juice – 1. Goblet cells secrete mucus – 2. Parietal cells secrete HCl and intrinsic factor (necessary for B12 absorption in intestine) – 3. Chief cells secrete pepsinogen (precursor to pepsin) 18-29 Stomach continued • 4. Enterochromaffinlike cells secrete histamine and serotonin • 5. G cells secrete gastrin • 6. D cells secrete somatostatin 18-30 HCl in Stomach • Is secreted into stomach lumen by proton pumps of epithelial parietal cells in response to the histamine secreted by ECL cells ; and ACh from vagus (parasympathetic stimulation) – These are indirect effects since release of histamine is due to gastrin release from G cells – Proton pump inhibitors (medicines) are common and work to reduce stomach acids (treat ulcers) 18-32 HCl in Stomach continued • Makes gastric juice very acidic which denatures proteins to make them more digestible • Also converts pepsinogen into pepsin – Pepsin is more active at low pHs 18-33 Digestion and Absorption in Stomach • Proteins are partially digested by pepsin • Carbohydrate digestion by salivary amylase is soon inactivated by acidity • Water, alcohol and aspirin are the only commonly ingested substances that are absorbed here 18-35 Small Intestine (SI) continued • Surface area increased by foldings and projections • Large folds are plicae circulares • Microscopic finger-like projections are villi • Cell apical hairlike membrane projections are microvilli 18-40 Intestinal Enzymes • Attached to microvilli are brush border enzymes – Enzyme active sites are exposed to chyme 18-43 Large Intestine or Colon • Has no digestive function of its own but absorbs H2O, electrolytes, B and K vitamins, and folic acid • Internal surface has no villi (relatively smooth) • Intestinal Flora: Contains large population of microflora – 400 different species of commensal bacteria • Which produce folic acid and vitamin K and ferment indigestible foods to produce fatty acids • And reduce ability of pathogenic bacteria to infect colon • Antibiotics can kill commensals 18-49 Fluid and Electrolyte Absorption in Colon • SI absorbs most water but colon absorbs 90% of water it receives – Begins with osmotic gradient set up by Na+/K+ pumps • Water follows by osmosis • Salt and water reabsorption stimulated by aldosterone • Colon can also excrete H2O via active transport of NaCl into intestinal lumen (an ANP influence) 18-51 Day 28 complete Accessory Organs:The Liver Functions of the Liver • Overall it over 500 functions! • Lipid metabolism: lipolysis, lipogenesis, synthesis of cholesterol • Protein metabolism: synthesizes the plasma proteins • (albumin, fibrinogen, alpha and beta globulins, and prothrombin); breaks down proteins and converts the to carbohydrates or lipid for storage. • Carbohydrate metabolism: helps to maintain normal blood glucose levels by; – breaking down glycogen into glucose and then secreting it into the blood – converting serum glucose into glycogen and triglycerides for storage Functions of the Liver • Detoxification: processes drugs and hormones; detoxifies substances such as alcohol or excretes drugs such as the antibiotics into bile. • Synthesis of bile salts: bile salts are used in the small intestine for the emulsification and absorption of lipids, cholesterol, phospholipids, and lipoproteins. • Storage: stores glycogen, vitamins and minerals. • Phagocytosis: Kupffer cells phagocytize RBCs, WBCs, bacteria, and toxins. Detoxification of Blood • Liver can remove hormones, drugs, and other biologically active molecules from blood by: – Excretion in bile – Phagocytosis by Kupffer cells – Chemical alteration of molecules • e.g. ammonia is produced by deamination of amino acids in liver – Liver then converts it to urea which is excreted in urine 18-64 The Gallbladder • Stores and concentrates bile continuously produced by liver – When SI is empty, sphincter of Oddi in common bile duct closes and bile is forced up into gallbladder • Expands as it fills with bile – When food is in SI, sphincter of Oddi opens, gall bladder contracts, and bile is ejected thru ducts into duodenum 18-69 The Pancreas • Has both endocrine and exocrine functions – Endocrine function performed by Islets of Langerhans cells • Secrete insulin and glucagon – Exocrine secretions include bicarbonate (HCO3-) solution and digestive enzymes • These pass in pancreatic duct to small intestine • Exocrine secretory units are acini 18-70 The Physiology of Digestion Regulation of Gastric Function • Extrinsic control of gastric function is divided into cephalic, gastric, and intestinal phases 18-78 Cephalic Phase • Refers to control by brain via vagus nerve • Stimulated by sight, smell, thought, and taste of food • Activation of vagus nerve stimulates: – Salivary glands to secrete saliva – Chief cells to secrete pepsinogen – G cells to secrete gastrin – ECL cells to secrete histamine – Parietal cells to secrete HCl 18-79 Gastric Phase • The presence of proteins, polypeptides and amino acids in the stomach raises the pH. This change in chemical nature, along with stomach distension, activates the gastric (stomach) phase. 18-81 Gastric Phase • Proteins, polypeptides and amino acids present in the stomach stimulate G cells to secrete gastrin and chief cells to secrete pepsinogen – Gastrin then stimulates ECL cells to secrete histamine which stimulates parietal cell secretion of HCl – This is a positive feedback mechanism: as more HCl and pepsinogen are secreted, more polypeptides and amino acids are liberated, and more digestive processes are stimulated. 18-81 Gastric Phase • As polypeptides leave the stomach and move into the duodenum, the pH begins to drop again and the gastric phase slows. 18-81 Summary of the Interactions Among Gastric Gland Cells and Secretions • 1. Presence of proteins in stomach, an increased pH, and stomach distension (ie: stretch) all stimulate G cells to secrete gastrin and chief cells to secrete pepsinogen. • 2. Gastrin stimulates ECL cells to secrete histamine. • 3. Histamine stimulates parietal cells to secrete HCL. • 4. HCl denatures proteins and activates pepsin from pepsinogen. • 5. Pepsin digests proteins into polypeptides. • 6. Polypeptides also stimulate G cells to secrete gastrin (a positive feedback effect). Intestinal Phase • Begins when chyme enters the small intestine • Arrival of chyme in duodenum causes a neural reflex that inhibits gastric motility and secretion – Fat in chyme stimulates SI to secrete enterogasterones--hormones that inhibit gastric motility and secretion • Include Somatostatin, Cholecystokinin, Secretin, and Gastric Inhibitory Peptide 18-83 Intestinal Phase • Enterogasterones secreted by intestines whem chyme arrives: – Somatostatin: inhibits stomach acid secretion. – Cholecystokinin: stimulates secretion of pancreatic enzymes; stimulates contraction of gall bladder; brings about a feeling of fullness after eating; slows gastric motility and acid secretion. 18-83 Intestinal Phase • Enterogasterones secreted by intestines whem chyme arrives: – Secretin: stimulates secretion of pancreatic HCO3and bile from the liver; inhibits acid production and gastric motility. – Gastric Inhibitory Peptide: Inhibits gastric motility and secretion; stimulates secretion of insulin from pancreas. 18-83 Digestion and Absorption of Carbohydrates • Most carbohydrates are ingested as starch-structured of glucose • Salivary amylase begins starch digestion in the mouth and continues for awhile in the stomach (until it is denatured by the low pH) 18-90 Digestion and Absorption of Carbohydrates • Pancreatic amylase secreted into duodenum converts starch to oligosaccharides – Oligosaccharides are hydrolyzed by small intestine brush border enzymes into monosaccharides – Monosaccharides are absorbed directly into the bloodstream 18-90 Digestion and Absorption of Proteins • Chemical digestion begins in stomach when pepsin digests proteins to form polypeptides • In small intestine, endopeptidases (trypsin, chymotrypsin, elastase) from pancreas cleave peptide bonds from interior of polypeptides • Also in small intestine exopeptidases (carboxypeptidase, aminopeptidase) cleave peptide bonds from ends of polypeptides. Carboxypeptidase is a pancreatic enzyme while aminopeptidase is a brush border enzyme. 18-91 Digestion and Absorption of Protein • Protein digestion in small intestine results in free amino acids, dipeptides, and tripeptides – Which are absorbed into small intestine cells where they are broken down into amino acids – Which are then secreted directly into the bloodstream 18-92 Digestion and Absorption of Lipids • Small amount of lipid chemical digestion begins in mouth via lingual lipase • No chemical digestion in stomach (except in infants who can digest milk fats) • Arrival of lipids in duodenum causes secretion of bile from gall bladder • Fat is emulsified by bile salt micelles – Form tiny droplets of fat – Greatly increases surface area for digestion by pancreatic lipase 18-93 Digestion and Absorption of Lipids continued • Pancreatic lipase then hydrolyzes exposed triglycerides to free fatty acids and monoglycerides which are then absorbed into epithelial cells 18-94 Digestion and Absorption of Lipids continued • Products of fat digestion are dissolved in micelles which move to the brush border 18-95 Digestion and Absorption of Lipids continued • Free fatty acids and monoglycerides leave micelles and are absorbed into epithelial cells – Inside epithelial cells, they are resynthesized into triglycerides and phospholipids, and then packaged into protein transport structures termed chylomicrons. 18-96