Overview of Gastrointestinal Function George N. DeMartino, Ph.D. Department of Physiology University of Texas Southwestern Medical Center Dallas, TX 75390 The gastrointestinal system Functions of the gastrointestinal system • Digestion • Absorption • Secretion • Motility • Immune surveillance and tolerance GI-OP-13 Histology of the GI tract Blood or Serosal Side Lumenal or Mucosal Side Structure of a villus Villus Lamina propria Movement of substances across the epithelial layer X Tight junctions Lumen Apical membrane X Blood Basolateral membrane X transcellular X X paracellular GI-OP-19 Histology of the GI tract Blood or Serosal Side Lumenal or Mucosal Side Motility in the gastrointestinal system Propulsion net movement by peristalsis Mixing for digestion and absorption Separation sphincters Storage decreased pressure GI-OP-42 Intercellular signaling in the gastrointestinal system • Neural • Hormonal • Paracrine GI-OP-10 Neural control of the GI system • Extrinsic nervous system autonomic central nervous system • Intrinsic (enteric) nervous system entirely with the GI system GI-OP-14 The extrinsic nervous system The intrinsic nervous system forms complete functional circuits Sensory neurons Interneurons Motor neurons (excitatory and inhibitory) Y Parasympathetic nerves regulate functions of the intrinsic nervous system Reflex control of gastrointestinal functions Vago-vagal reflex Afferent Salivary Glands Composition of Saliva O Proteins α−amylase lipase lysozyme mucus lactoferrin RNase et al O Electrolyte solution water Na+ , K + HCO3- Functions of saliva • Oral protection • Oral hygiene • Lubrication • Digestion buffering of hot, cold, acid, base bacteriostatic swallowing carbohydrates and lipids GI-ME-11 Structure of the esophagus Pharynx Upper Esophageal Sphincter (UES) Skeletal muscle Skeletal and smooth muscle Smooth muscle Diaphragm Lower Esophageal Sphincter (LES) Stomach GI-010 Regulation of the UES during a swallow Reflex relaxation (neural) Reflex contraction (neural) Persistalsis Regulation of the UES during a swallow Reflex relaxation (neural) VIP (NO ?) Reflex contraction (myogenic) Anatomical and functional divisions of the stomach LES Pyloric gland area Fundus Orad Gastric juice pylorus Oxyntic gland G cell Caudad duodenum Oxyntic gland area Gastrin Antrum Body (Corpus) GI-S-15 Mechanism of acid secretion by the parietal cell H2O Lumen Cl- K+ H2O K+ Na+ H+ Cl- ATP ADP K+ Cl- ATP ADP Na+ H20 H+ + OH CO2 Blood + HCO3Carbonic anhydrase GI-S-07 Stimulation of acid secretion in parietal cells Receptors Histamine (H2) G Gastrin G ACh AC PL-C PL-C G + H H+ Lumen GI-S-13 Stimulation of acid secretion in parietal cells Receptors Histamine (H2) G Gastrin G ACh AC PL-C PL-C G cAMP Protein kinase A Sequestered H+ / K+ pumps IP3 + DAG Ca2+ Substrates Membrane-exposed H+ / K+ pumps Protein kinase C Substrates H+ Lumen Sequestered H+ / K+ pumps GI-S-13 Cephalic phase of acid secretion vagal nucleus vagus nerve thought, sight, smell, taste, or chewing of food H+ ACh GRP Parietal cell ECL cell G cell Histamine Gastrin Efferent pathways circulation GI-S-05 vagal nucleus Gastric phase of acid secretion vagus nerve distension sensed by mechanoreceptors distension in the stomach, presence of amino acids and peptides H+ Amino acids and peptides ACh G cell GRP ACh Efferent pathways Afferent pathways Parietal cell ECL cell Histamine Gastrin circulation GI-S-06 Protection of the epithelial lining of the stomach pH 2 HCO3- HCO3- Gastric lumen Mucus layer pH 7 Mucus GI-S-19 Motility in the stomach • Reservoir storage without increased pressure • Grinding and mixing mechanical disruption for digestion and absorption • Regulated pumping optimal delivery to duodenum GI-S-32 The gastrointestinal system Small Intestine Digestion Absorption Secretion Motility Pancreatic Secretion Aqueous Component (ductule cells) water bicarbonate Function: acid neutralization Enzymatic Component (acinar cells) proteases lipases saccharidases Function: digestion Intestinal phase of pancreatic secretion vagal nucleus vagus nerve afferent pathways for vagal reflex acid and digestion products in the duodenum protein I cells amino acids peptides fat H+ S cells circulation CCK efferent pathways for vagal reflex HCO3H2O Secretin Ach Enzymes ductule cells pancreas acinar cells GI-SILPGB-02 Secretion from the liver and gallbladder Figure15 Na+ Cl - K+ Liver Ca2+ Bile acids water Portal circulation Figure11 Secretin HCO3Na+ H20 Gallbladder HCO3ClNa+ H20 CCK Sphincter of Oddi Bile Duodenum Figure14 Ach Bile acids Ileum Functions of Bile • Emulsification of dietary lipids required for lipid digestion • Solubilization of lipid digestion products required for lipid absorption • Excretion of waste products bilirubin and cholesterol GI-SILPGB-30 Organic components of bile • Bile acids / bile salts 70% • Phospholipids 20% • Cholesterol 5% • Bilirubin 1% • Everything else 4% GI-SILPGB-40 Components of bile Bile acids package products of lipid digestion into mixed micelles for absorption Products of lipid digestion Cholesterol + -- + -- Lysolecithin Monoglyceride + Free fatty acid -- - + Mixed micelle - GI-SILPGB-36 Digestion and absorption in the small intestine Proteins degradation to amino acids and peptides combined action of lumenal and membranebounds proteases absorption by multiple transporters Carbohydrates degradation to monosaccharides combined action of lumenal and membranebounds proteases absorption by several transporters Lipids Absorption of monosaccharides in the small intestine Na+/ K+ ATPase K+ SGLT1 ATP¤ADP Na+ Glucose / Galactose Na+ Fructose Fructose Glucose / Galactose Glut 2 Glut 5 Lumen (Apical) Blood (Basolateral) GI-SILPGB-16 Fluid balance in the GI tract ~ 20% total body water ! 9000 ml 8900 ml Volume entering intestines Volume absorbed by intestines 100 ml Volume excreted Important Principle The absorption of water is dependent on and proportional to the absorption of solutes GI-LI-25 Bad things happen when solutes are not absorbed Jejunum Lactose Ileum Colon Na+ glucose + galactose H2O H2O Normal SCFA Lactose Lactose H2O CO2 Diarrhea Lactose H2O Lactase deficiency H2O GI-LI-24