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Digestion, Absorption, Transport Digestion Breakdown of food molecules for absorption into circulation Mechanical: Breaks large food particles to small Chemical: Breaking of covalent bonds by digestive enzymes Absorption and transport Molecules are moved out of digestive tract and into circulation for distribution throughout body Digestive System Regulation Nervous regulation Involves enteric nervous system Types of neurons: sensory, motor, interneurons Coordinates peristalsis and regulates local reflexes Chemical regulation Production of hormones Gastrin, secretin Production of paracrine chemicals Histamine Help local reflexes in ENS control digestive environments as pH levels Digestive System Anatomy Digestive tract Accessory organs Alimentary tract or canal GI tract Primarily glands Regions Mouth or oral cavity Pharynx Esophagus Stomach Small intestine Large intestine Anus Peritoneum and Mesenteries Peritoneum Visceral: Covers organs Parietal: Covers interior surface of body wall Retroperitoneal: Behind peritoneum as kidneys, pancreas, duodenum Mesenteries Routes which vessels and nerves pass from body wall to organs Greater omentum Lesser omentum Digestive Tract Histology Oral Cavity Mouth or oral cavity Lips (labia) and cheeks Palate: Oral cavity roof Vestibule: Space between lips or cheeks and alveolar processes Oral cavity proper Hard and soft Palatine tonsils Tongue: Involved in speech, taste, mastication, swallowing Teeth Two sets Primary, deciduous, milk: Childhood Permanent or secondary: Adult (32) Types Incisors, canine, premolar and molars Tooth structure: Salivary Glands Produce saliva Prevents bacterial infection Lubrication Contains salivary amylase Breaks down starch Three pairs Parotid: Largest Submandibular Sublingual: Smallest Pharynx and Esophagus Pharynx Nasopharynx Oropharynx: Transmits food normally Laryngopharynx: Transmits food normally Esophagus Transports food from pharynx to stomach Passes through esophageal hiatus (opening) of diaphragm and ends at stomach Hiatal hernia Sphincters Upper Lower Phases of Deglutition (Swallowing) Deglutition (Swallowing) Three phases Voluntary Bolus of food moved by tongue from oral cavity to pharynx Pharyngeal Reflex: Upper esophageal sphincter relaxes, elevated pharynx opens the esophagus, food pushed into esophagus Esophageal Reflex: Epiglottis is tipped posteriorly, larynx elevated to prevent food from passing into larynx Functions Ingestion: Introduction of food into stomach Mastication: Chewing Propulsion Deglutition: Swallowing Peristalsis: Moves material through digestive tract Stomach Anatomy: Openings Gastroesophageal: To esophagus Pyloric: To duodenum Regions Cardiac Fundus Body Pyloric Stomach Anatomy cont. Rugae: Folds in stomach when empty Gastric pits: Openings for gastric glands Contain cells Surface mucous: Mucus Mucous neck: Mucus Parietal: Hydrochloric acid and intrinsic factor Chief: Pepsinogen Endocrine: Regulatory hormones Stomach Histology: Layers Serosa or visceral peritoneum: Outermost Muscularis: Three layers Outer longitudinal Middle circular Inner oblique Submucosa Mucosa Phases of Gastric Activity I Hydrochloric Acid Production Phases of Gastric Activity II Movements in Stomach Phases of Gastric Activity III Gastric hormones: Small Intestine Site of greatest amount of digestion and absorption Divisions Modifications Duodenum Jejunum Ileum: Peyer’s patches or lymph nodules Circular folds or plicae circulares, villi, lacteal, microvilli Cells of mucosa Absorptive, goblet, granular, endocrine Small Intestine Secretions Mucus Digestive enzymes Protects against digestive enzymes and stomach acids Disaccharidases: Break down disaccharides to monosaccharides Peptidases: Hydrolyze peptide bonds Nucleases: Break down nucleic acids Duodenal glands Stimulated by vagus nerve, secretin, chemical or tactile irritation of duodenal mucosa Movement in small intestine: Mixing: Segmental contraction that occurs in small intestine Secretion: Lubricate, liquefy, digest Digestion: Mechanical and chemical Absorption: Movement from tract into circulation or lymph Elimination: Waste products removed from body Accessory Glands and Structures Liver Exocrine Pancreas Gall bladder Pancreatic duct Hepatic Portal System Duodenum and Pancreas Duct System Gallbladder Bile is stored and concentrated Stimulated by cholecystokinin and vegal stimulation Dumps into small intestine Production of gallstones possible Drastic dieting with rapid weight loss Liver Lobes Major: Left and right Minor: Caudate and quadrate Ducts Common hepatic Cystic From gallbladder Common bile Joins pancreatic duct at hepatopancreatic ampulla Functions of the Liver Bile production Storage Hepatocytes remove ammonia and convert to urea Phagocytosis Glycogen, fat, vitamins, copper and iron Nutrient interconversion Detoxification Salts emulsify fats, contain pigments as bilirubin Kupffer cells phagocytize worn-out and dying red and white blood cells, some bacteria Synthesis Albumins, fibrinogen, globulins, heparin, clotting factors Bile …each day around 600 ml of bile is produced… Bile acid Phospholipids Cholesterol Bilirubin Waste products Electrolytes Mucin Blood and Bile Flow Pancreas Anatomy Endocrine Exocrine Pancreatic islets produce insulin and glucagon Acini produce digestive enzymes Regions: Head, body, tail Secretions Pancreatic juice (exocrine) Trypsin Chymotrypsin Carboxypeptidase Pancreatic amylase Pancreatic lipases Enzymes that reduce DNA and ribonucleic acid Exocrine Pancreas – Enzymes Trypsinogen Chymotrysinogen Carboxypeptidases Pro-elastase Phospholipase pancreatic lipase Pancreatic amylase Enzymes that reduce DNA and ribonucleic acid Bicarbonate Ion Production Lipoproteins Types Chylomicrons VLDL LDL Enter lymph Transports cholesterol to cells HDL Transports cholesterol from cells to liver Large Intestine Cecum Colon Ascending, transverse, descending, sigmoid Rectum Blind sac, vermiform appendix attached Straight muscular tube Anal canal Internal anal sphincter (smooth muscle) External anal sphincter (skeletal muscle) Hemorrhoids: Vein enlargement or inflammation Large Intestine: Extends from ileocecal junction to anus Consists of cecum, colon, rectum, anal canal Movements sluggish (18-24 hours) Histology of Large Intestine Transport and Secretion by Large Intestine Mucus provides protection Parasympathetic stimulation increases rate of goblet cell secretion Pumps Exchange of bicarbonate ions for chloride ions Exchange of sodium ions for hydrogen ions Bacterial actions produce gases called flatus Water and Ions: Water Can move in either direction across wall of small intestine depending on osmotic gradients Ions Sodium, potassium, calcium, magnesium, phosphate are actively transported Movement in Large Intestine Mass movements Local reflexes in enteric plexus Gastrocolic: Initiated by stomach Duodenocolic: Initiated by duodenum Defecation reflex Common after meals Distension of the rectal wall by feces Defecation Usually accompanied by voluntary movements to expel feces through abdominal cavity pressure caused by inspiration Reflexes in Colon and Rectum: Effects of Aging Decrease in mucus layer, connective tissue, muscles and secretions Increased susceptibility to infections and toxic agents Ulcerations and cancers Atherosclerosis is an Inflammatory Disease Vessel Lumen Monocyte Endothelium Cytokines Growth Factors Metalloproteinases Cell Proliferation Matrix Degradation Foam Cell Ross R. N Engl J Med 1999;340:115-126. Macrophage Intima Lipoprotein Classes and Inflammation Chylomicrons, VLDL, and their catabolic remnants LDL HDL > 30 nm 20–22 nm 9–15 nm Potentially proinflammatory Potentially antiinflammatory Doi H et al. Circulation 2000;102:670-676; Colome C et al. Atherosclerosis 2000; 149:295-302; Cockerill GW et al. Arterioscler Thromb Vasc Biol 1995;15:1987- LDL is composed of a core of 1500 molecules of cholesterol enclosed in layers of phospholipid and unesterified cholesterol molecules. A large protein called apoprotein B-100 is embedded in this hydrophilic layer. LDL is generated by the bodies fat-transport system via two mechanisms; the exogenous and the endogenous pathways. Structure of LDL Surface Monolayer of Phospholipids and Free Cholesterol apoB Hydrophobic Core of Triglyceride and Cholesteryl Esters Murphy HC et al. Biochemistry 2000;39:9763-970. The exogenous pathway begins in the intestine, and commences as the dietary fats become packaged into lipoprotein particles called chylomicrons. Chylomicrons contain phospholipid, cholesterol, apolipoproteins (apo), for example apo B48, apo A-1, apo 11, C –11 and apo-E. Chylomicrons contain phospholipid, cholesterol, apolipoproteins (apo), for example apo B48, apo A-1, apo 11, C –11 and apo-E. Role of LDL in Inflammation LDL Readily Enter the Artery Wall Where They May be Modified Vessel Lumen LDL Endothelium Oxidation of Lipids and ApoB Aggregation LDL Hydrolysis of Phosphatidylcholine to Lysophosphatidylcholine Other Chemical Modifications Modified LDL Modified LDL are Proinflammatory Steinberg D et al. N Engl J Med 1989;320:915-924. Intima Modified LDL Stimulate Expression of MCP-1 in Endothelial Cells Vessel Lumen Monocyte LDL MCP-1 LDL Endothelium Modified LDL Monocyte chemotactic protein-1 Navab M et al. J Clin Invest 1991;88:2039-2046. Intima Differentiation of Monocytes into Macrophages Vessel Lumen Monocyte LDL MCP-1 Endothelium LDL Intima Modified LDL Macrophage Steinberg D et al. N Engl J Med 1989;320:915-924. Modified LDL Promote Differentiation of Monocytes into Macrophages Modified LDL Induces Macrophages to Release Cytokines That Stimulate Adhesion Molecule Expression in Endothelial Cells Vessel Lumen Monocyte LDL Adhesion Molecules MCP-1 Cytokines Endothelium LDL Modified LDL Macrophage Nathan CF. J Clin Invest 1987;79:319-326. Intima Macrophages Express Receptors That Take up Modified LDL Vessel Lumen Monocyte LDL Adhesion Molecules MCP-1 Endothelium LDL Modified LDL Taken up by Macrophage Foam Cell Macrophage Steinberg D et al. N Engl J Med 1989;320:915-924. Intima Macrophages and Foam Cells Express Growth Factors and Proteinases Vessel Lumen Monocyte LDL Adhesion Molecules Cytokines Macrophage MCP-1 LDL Modified LDL Foam Cell Ross R. N Engl J Med 1999;340:115-126. Endothelium Intima Growth Factors Metalloproteinases Cell Proliferation Matrix Degradation The Remnants of VLDL and Chylomicrons are Also Proinflammatory Monocyte Vessel Lumen Remnant Lipoproteins Adhesion Molecules Cytokines Macrophage Endothelium MCP-1 Remnants Modified Remnants Foam Cell Doi H et al. Circulation 2000;102:670-676. Intima Growth Factors Metalloproteinases Cell Proliferation Matrix Degradation Structure of HDL apoA-I apoA-II Rye KA et al. Atherosclerosis 1999;145:227-238. Surface Monolayer of Phospholipids and Free Cholesterol Hydrophobic Core of Triglyceride and Cholesteryl Esters HDL Prevent Formation of Foam Cells Vessel Lumen Monocyte LDL Adhesion Molecules MCP-1 Endothelium LDL Modified LDL Cytokines Macrophage Foam Cell HDL Promote Cholesterol Efflux Miyazaki A et al. Biochim Biophys Acta 1992;1126:73-80. Intima HDL Inhibit the Oxidative Modification of LDL Vessel Lumen Monocyte LDL Adhesion Molecules MCP-1 Endothelium LDL Modified LDL Cytokines Macrophage Foam Cell HDL Promote Cholesterol Efflux Mackness MI et al. Biochem J 1993;294:829-834. HDL Inhibit Oxidation of LDL Intima Inhibition of Adhesion Molecules HDL Inhibit Adhesion Molecule Expression LDL Vessel Lumen Monocyte Adhesion Molecules MCP-1 Endothelium LDL Modified LDL Cytokines Macrophage HDL Inhibit Oxidation of LDL Foam Cell HDL Promote Cholesterol Efflux Intima Cockerill GW et al. Arterioscler Thromb Vasc Biol 1995;15:1987-1994. Macrophage Functions in Atherogenesis Activation