MBBS Year 1 Gastrointestinal Lectures PDF

Prof GE Mann, Waterloo Campus (Email: [email protected]) MBBS Year 1 Gastrointestinal Lectures L1: Overview of the digestive system L2: Digestion and absorption of nutrients L3: Salivary, gastric and pancreatic secretions L4: Bile and biliary system L5: Motility of the gut Physiology, 5th...

Prof GE Mann, Waterloo Campus (Email: [email protected]) MBBS Year 1 Gastrointestinal Lectures L1: Overview of the digestive system L2: Digestion and absorption of nutrients L3: Salivary, gastric and pancreatic secretions L4: Bile and biliary system L5: Motility of the gut Physiology, 5th Edition, eds. RM Berne, MN Levy, BM Koeppen, BA Stanton (2004) (see Chapters 31-33) [see also recent Editions] Medical Physiology, eds. WF Boron & EL Boulpaep (2003) Color Atlas of Physiology, 4th Edition, eds. A. Despopoulos & S. Silbernagl, (1991) 1 MBBS Year 1 Gastrointestional Lectures L3: Salivary, gastric and pancreatic secretions Learning objectives Name the salivary glands and the major kinds of salivary secretions and their function Describe how salivary secretion is controlled Describe factors which influence gastric juice secretion and HCl concentration in the stomach Explain how mucus and bicarbonate secretion create a gastric mucosal barrier Describe cephalic, gastric and intestinal phases of acid secretion Describe constituents and physiological functions of pancreatic juice Describe the factors causing release of secretin and cholecystokinin and how these intestinal hormones modify the composition of pancreatic juice 2 3 4  Functions of saliva 5 O. Ekberg (ed.), Dysphagia, Medical Radiology. Diagnostic Imaging, ‘Saliva and control of its Secretion’, Ekstrom et al., DOI: 10.1007/174_2011_481, Springer-Verlag Berlin Heidelberg 2012 6  Acinar cells: transmitters, receptors, and intracellular pathways 7 O. Ekberg (ed.), Dysphagia, Medical Radiology. Diagnostic Imaging, ‘Saliva and control of its Secretion’, Ekstrom et al., DOI: 10.1007/174_2011_481, Springer-Verlag Berlin Heidelberg 2012  Physiological changes at old age contributing to hyposalivation 8 O. Ekberg (ed.), Dysphagia, Medical Radiology. Diagnostic Imaging, ‘Saliva and control of its Secretion’, Ekstrom et al., DOI: 10.1007/174_2011_481, Springer-Verlag Berlin Heidelberg 2012 Learning objectives – Gastric acid secretion Describe factors which influence gastric juice secretion and HCl concentration in stomach Explain how mucus and bicarbonate secretion create a gastric mucosal barrier Describe cephalic, gastric and intestinal phases of acid secretion 9  Functional adaptation of the stomach epithelium during HCl secretion Stomach is an exocrine organ, secreting a large acid volume after a meal. Secretion also contains pepsin which initiates protein digestion, a process continued in the intestine by pancreatic enzymes. Gastric surface is protected by thin film of mucous which is produced constantly by surface epithelial cells. Another exocrine product is intrinsic factor, a glycoprotein that combines with vitamin B12 aiding absorption in the ileum. Entire surface of glandular stomach is a simple columnar epithelium of surface mucous cells, which also line numerous tubular invaginations and gastric pits. Upon stimulation of HCl by histamine (and/or Ach, gastrin) the parietal cells undergo structural changes, forming a markedly increased tubulovesicular system for the secretion of protons. 10  Phases of Gastric Acid Secretion Acid secretion divided into basal (fasting) and stimulated (post- prandial) phases, cephalic, gastric and intestinal phases 11 Only small portion of material propelled through pylorus to duodenum. Most of contents returned to body/corpus of stomach for pulverization/shearing of solid particles, known as retropulsion. Particles >2mm retained in stomach but eventually emptied into duodenum during interdigestive phase beginning about 2 h or more after eating 12 13 Role of blood flow in supply of nutrients for HCl secretion and buffering via HCO3 14  Gastric Mucosal Defence H+ H+ H+ pH 1-2 Mucus gel pH 7 HCO3- HCO3- HCO3- Tight junctions Surface mucus cells circulation 15 with permission Prof Rod Dimaline, Physiology, Univ. Liverpool Resting parietal cell Activated parietal cell Tubulovesicles Intracellular canaliculi 16 with permission Prof Rod Dimaline, Physiology, Univ. Liverpool 17 Soll’s three receptor model Dimaline model gastrin ACh gastrin ACh CCK2 ECL-cell histamine histamine CCK2 M3 CCK2 M3 H2 H2 + + 18 HCl HCl Physiological stimulation of gastric acid secretion HCl Gastric lumen epithelium H2 CCK-2 ECL-cell histamine gastrin CCK-2 bloodstream 19 with permission Prof Rod Dimaline, Physiology, Univ. Liverpool  Acid Proton pump inhibitor Food (eg omeprazole) x G-cell D-cell histamine ECL-cell x H2 antagonist (eg famotidine) Gastrin Gastrin 20 with permission Prof Rod Dimaline, Physiology, Univ. Liverpool  Control of G-cell function (antrum) Protein/peptides/amino H+ acids + + G-cell D-cell Gastrin releasing + - peptide, GRP somatostatin circulation Blood supply carries H+ away, helps antioxidant Gastrin function 21 with permission Prof Rod Dimaline, Physiology, Univ. Liverpool 22  Omeprazole Brief Clinical Summary Activated drug forms disulphide link with H+,K+ -ATPase and block enzyme unreversibly Inhibits gastric HCl secretion by ~80% over 24h Therapy for peptic ulcer and reflux oesophagitis Quicker relief and accelerated healing rates for peptic ulcers compared with H2-antagonists 23 Consequences of damaged mucosa 24 25 26 Note that fat entering the small intestine serves to inhibit acid secretion by parietal cells in the stomach – this is an example of the ‘intestinal phase’ of acid secretion, with key intestinal hormones circulating via the bloodstream to target acid secreting cells in the stomach. 27 Learning objectives – Pancreatic secretion Describe the physiological function of pancreatic juice Describe the factors causing release of secretin and cholecystokinin and how these intestinal hormones modify the composition of pancreatic juice 28 29 Secretion of pancreatic juice Highest rate of protein synthesis of any secretory tissue with exception of lactating mammary gland Aqueous component rich in HCO3 which neutralises duodenal content and enzyme component Proteolytic enzymes – trypsinogen, chymotrypsinogen, procarboxypolypeptidase, ribonuclease, deoxyribonuclease Amylase - starch & glycogen Lipase - hydrolyses neutral fat into glycerol & fatty acids. 30 Pancreatic HCO3- secretion and NaCl-rich fluid 31 32 Exocrine pancreatic enzyme synthesis and secretion: Four traces on the left illustrate the time course of secretory proteins moving through pancreatic cell compartments. To radioactively label new proteins, pancreatic acinar pulsed with [3H]-labelled amino acids and after specific times the cells were fixed and distribution of radioactivity determined using autoradiography (Data from Adler et al., Gastroenterology 100:537-543, 1991). Note that pancreatic acinar cells can adjust enzyme secretion for different diets, e.g. carbohydrate vs protein. 33 34