+.1 Studúes OlTlæ Ftrnctíon OJTIrc Humanfolonts And,Iß R.ole InTlæ Riegulø;tíon OÍ Cústríß Drnptging David R. Fone Departments of Medicine and Gastroenterology, Royal Adelaide Hospital University of Adelaide August 1990 Table of Contents TABLE OF CONTENTS . SUMMARY vil DECLARATION...... X DED|CAT|ON.. .. ... xt ACKNOWLEDGMENTS xil CHAPTER 1 ANATOMY OF THE PYLORUS 1.1 INTRODUCTION.. 1 1.2 MUSCULAR ANATOMY 2 1.3 MUCOSAL ANATOMY 4 1.4 NEURALANATOMY 1.4.1 Extrinsic lnnervation of the Pylorus 5 1.4.2 lntrinsic lnnervation of the Pylorus 7 1.5 INTERSTITIAL CELLS OF CAJAL 8 1.6 CONCLUSTON 9 CHAPTER 2 MEASUREMENT OF PYLORIC MOTILITY 2.1 INTRODUCTION 10 2.2 METHODOLOG ICAL CHALLENGES 2.2.1 The Anatomical Mobility of the Pylorus . 10 2.2.2 The Narrowness of the Zone of Pyloric Contraction 12 2.3 METHODS USED TO MEASURE PYLORIC MOTILITY 2.3.1 lntraluminal Techniques 2.3.1.1 Balloon Measurements. 12 t 2.3 1.2 lntraluminal Side-hole Manometry . 13 2.3 1.9 The Sleeve Sensor 14 2.3 1.4 Endoscopy. 16 2.3 1.5 Measurements of Transpyloric Flow . 16 2.3 'I .6 lmpedance Electrodes 16 2.3.2 Extraluminal Techniques For Recording Pyl;'; l'¡"r¡iit¡l 2.3.2.'t Strain Gauges . 17 2.3.2.2 lnduction Coils . 17 2.3.2.3 Electromyography 17 2.3.3 Non-lnvasive Approaches For Recording 2.3.3.1 Radiology :ï:: Y:1":'1 18 2.3.9.2 Ultrasonography . 1B 2.3.3.3 Electrogastrography 19 2.3.4 ln Vitro Studies of Pyloric Muscle 19 2.4 CONCLUSTON. 19 CHAPTER 3 MEASUREMENT OF GASTR¡C EMPTYING 3.1 INTRODUCTION. 20 3.2 INVASIVETECHNIQUES FOR MEASURING GASTRIC EMPryING IN HUMANS 3.2.1 lntubation/Aspiration of Gastric Contents. 20 aã NON-INVASIVE TECHNIQUES FOR MEASURING GASTRIC EMPryING 3.3.'l Radiology 21 3.3.2 Ultrasonography . 22 3.3.3 Applied Potential Tomography and lmpedance Epigastrography 22 3.3.4 Absorption Kinetics of Orally Administered Drugs . 22 3.3.5 RadionuclideTechniques 23 3.3.5.1 Radionuclide Markers 23 3.3.5.2 OtherMethodological lssues 25 s.s.s.s Data Acquisition and Processing 27 3.3.5.4 Geometrical Errors of Radionuclide Methods 27 3.3.5.5 Limitations of Radionuclide Methods 28 3.4 CONCLUSTON 28 CHAPTER 4 COORDINATED PATTERNS OF PYLORIC MOTILITY 4.1 INTRODUCTION.. 29 4.1.1 Definition of Antropyloroduodenal Coordination 30 4.2 COORDINATED PYLORIC MOTILITY DURING FASTING. 30 4.2.1 Patterns of Propagated Motility During Fasting 30 4.2.2 Localized Pyloric Motility During Fasting . 34 4.3 COORDINATED PYLORIC MOTILITY IN THE FED STATE . 35 4.3.1 Patterns of Propagated Motility in the Fed State 35 4.3.2 Localized Pyloric Motility in the Fed State . 37 4,4 CONCLUSION 39 It CHAPTER 5 CONTROL OF PYLORIC MOTILITY s.1 INTRODUCTION. 40 5.2 ELECTROMECHANICAL PFìOPERTIES OF PYLORIC SÍUOOTH MUSCLE 5.2.1 Characteristics of the Electrical Control and Response Activity of Smoolh Muscle Cells at the Distal Pyloric Muscle Loop . 42 5.2.2 Transmission of Electrical Activity Across the Pylorus 44 5.2.3 Mechanisms for the Modulation of Pyloric Electrical Activity by Neurotransmitters and Gastrointestinal Hormones. 46 5.2.4 Conclusion 46 5.3 CENTRAL NERVOUS SYSTEM CONTROLOF PYLORIC T/OTOR FUNCTION 46 5.3.1 Evidence for Control of the Pylorus by the Vagus Nerve . 47 5.3.1.1 Excitatory lnnervation of the Pylorus by the Vagus . 47 5.3.1.2 lnhibitory lnnervation of the Pylorus by the Vagus . 47 5.3.2 Sympathetic Control of Pyloric Motility 48 5.4 CONTROL OF THE PYLORUS BY THE SMALL INTESTINE 49 5.4.1 The Effect of lntraluminal Small lntestinal Stimuli on Pyloric Motility 49 5.4.1.1 lntraluminal Nutrients 49 5.4.1.2 Small lntestinal Acidification . 50 5.4.2 Sile and Nature of Mucosal Receptors in the Small lntestine . 50 5.4.3 Candidate Local Neural Mechanisms for Mediating the Small lntestinal Control of Pyloric Motilily 51 5.4.3.1 Neural Pathways Connecting the Duodenum to the Pylorus. 52 5.4.3.2 Pathways Connecting the Antrum to the Pylorus . 52 5.4.3.3 Conclusion 53 5.5 C,ONTROLOF THE PYLORUS BY GASTROINTESTINAL HORMONES 53 5.5.1 Cholecystokinin . 53 5.5.2 Secretin 55 5.s.3 Peptide YY . .55 5.5.4 Olher Candidale Hormones . .56 5.5.5 Summary .56 s.6 CONCLUSTON 57 CHAPTER 6 THE MECHANICAL ROLE OF THE PYLORUS 6.1 INTRODUCTION. 58 6.2 THE PYLORUS AS A GASTROINTESTINAL SPHINCTER 59 6.3 THE MECHANICAL EFFECT OF LOCALIZED PYLORIC CONTRACTION . 60 6.3.1 The Pylorus and Liquid Gastric Emptying 60 6.3.2 The Pylorus and Gastric Emplying of Digestible Solids 62 6.3.3 The Gastric Emptying of Non-Digestible Solids During Fasting 65 6.3.4 The Pylorus and Duodenogastric Reflux 65 6.4 CONCLUSION 65 itt CHAPTER 7 METHODS USED TO STUDY PYLORIC MOTILITY AND GASTRIC EMPTYING IN THIS THESIS 7.1 INTRODUCTION. 66 7.2 SELECTION OF SUBJECTS 66 7.3 i/IANOI/ETRIC TECH N IQIJ E 7.3.1 lntubationTechnique .67 7.3.2 Manometric Methods 7.3.2.1 Design of the Manometric Assembly 67 7.3.2.2 Recording of lntraluminal Pressures 69 7.3.3 Measurement of Transmucosal Potential Difference 7.s.s.'l Background 70 7.3.3.2 Technique 70 7.4 MEASUREMENT OF GASTRIC EMPTYING 72 7.5 DATA ANALYSIS 7.5.1 Analysis of Recordings . 72 7.5.2 Analysis of Gastric Emptying Measurements 75 7.5.3 Statistical Tests . 75 CHAPTER 8 TECHNICAL ASPECTS INVOLVED IN INTERPRETING COMBINED SLEEVE/SIDE.HOLE PYLORIC MANOMETRY IN HUMANS 8.1 INTRODUCTION.. .. 76 8.2 A STUDY OF THE COMPARATIVE EFFECTS OF DUODENAL AND ILEAL INTUBATION ON PYLORIC, ANTRAL AND DUODENAL h/OTILITY AND THE GASTRIC EMPTYING OF A SOLID MEAL 8.2.1 Background 76 8.2.2 Materials and Melhods 8.2.2.1 Subjects 77 8.2.2.2 Experimental Protocol 77 8.2.2.9 Data Analysis . 78 8.2.3 Results 78 8.2.3.1 GastricEmptying 78 8.2.3.2 Motility 81 8.2.3.3 Relationships Between Gastric Emptying, Motility and lntubation Time B2 8.2.4 Summary of Results 82 8.3 AN EVALUATION OF THE NORMAL PATTERNS OF HUMAN PYLORIC AND ANTRAL I/OTILITY WITH A NOVEL ANTRAL WALL MOTION DETECTOR 8.3.1 lntroduction 82 8.3.2 Materials and Methods 8.3.2.r subjects 83 8.3.2.2 Experimental Protocol .83 tv 8.3.2.3 Measurement of Motility . 83 8.3.3 Data Analysis 8.3.3.1 Analysis of Records 84 8.3.3.2 Statistical Methods 87 8.3.4 Resulls 8.3.4.1 Subject Tolerance and Sensor Positioning 87 8.3.4.2 Antral Motility . 87 8.3.4.3 lsolated Pyloric Pressure Waves 92 8.3.5 Summary of Results 96 8.4 DISCUSSION 96 8.s CONCLUSTON 102 CHAPTER 9 CONTROL OF PYLORIC MOTILITY BY STIMULATION OF SMALL INTEST¡NAL RECEPTORS 9.1 INTRODUCTION 103 9.2 A STUDY OF THE ROLE OF MUSCARINIC MECHANISMS IN THE PYLORIC i/lOTOR RESPONSE TO INTRADIJODENAL DEXTFìOSE IN HUMANS 9.2.1 Background 103 9.2.2 Methods 9.2.2.1 Subjects 104 9.2.2.2 Experimental Design . 104 9.2.2.3 Pressure Measurement 106 9.2.2.4 DalaAnalysis...... 106 9.2.2.s Statistical Analysis . 106 9.2.3 Results 106 9.2.3.1 Pyloric Motor Responses lo lntraduodenal Dextrose 107 9.2.3.2 Antroduodenal Motor Changes 112 9.2.4 Summary of Results 114 9.3 A STUDY OF THE EFFECT OF DISTAL SMALL INTESTINALTRIGLYCERIDE INFUSION ON PYLORIC, ANTRAL AND DUODENAL MOTILITY, GASTRIC EMPTYING AND THE INTRAGASTRIC DISTRIBUTION OF A SOLID MEAL 9.3.1 Background 114 9.3.2 Materials and Methods 9.3.2.1 Subjects 115 9.3.2.2 Experimental Protocol 115 9.3.2.3 Manometric Methods . 118 9.s.2.4 Data Analysis . 118 L9.2.5 Statistical Analysis . 118 9.3.3 Results 9.3.3.1 Subject Tolerance and Assembly Position 119 9.s.s.2 Gastric Emplying Profile 119 9.3.3.3 Antropyloroduodenal Motor Response . 124 9.3.3.4 Correlation Between Gastric Emptying and Motility . 124 9.3.4 Summary of Results '127 9.4 DISCUSSION 128 e.s coNcLUStoN 132 Y CHAPTER 10 A STUDY OF PYLORIC MOTILITY DURING THE DELAYED GASTRIC EMPTYING INDUCED BY COLD STRESS 10.1 |NTRODUCTION.. 134 10.2 i/ATERIALS AND METHODS '1O.2.1 Subjecls ... 134 10.2.2 Experimental Protocol ... 135 10.2.3 Manometric Methods .. 136 10.2.4 Data and Statistical Analysis ... 136 10.3 RESULTS 10.3.1 Subject Tolerance of Cold Stress 136 10.3.2 Gastric Emptying 137 10.3.3 Pyloric MotilitY 141 10.3.4 Antral and Duodenal Motility 10.3.4.1 Antral Motility . 141 10.3.4.2 Duodenal MotilitY 141 10.3.5 Relationship Between Motility and Gastric Emptying . '147 10.4 SUMMARY OF STUDY 148 10.5 DISCUSSION 149 10.6 CONCLUSION 150 CHAPTER 11 FUTURE MANOMETR¡C INVEST¡GAT¡ON OF NORMAL PYLORIC MOTOR FUNCTION IN HUMANS 11.1 INTRODUCTION 1s1 11.2 RECONíIúENDATIONS FOR IT/PROVED i/ETHODOLOGICAL APPROACHES FOR PYLORICMANOMETRY.... 151 11.3 INVESTIGATION OF THE COORDINATED PATTERNS AND PHYSIOLOGICAL CONTROL OF HUMAN PYLORIC MOTILITY 152 11.4 THE IMPORTANCE OF THE HUI/AN PYLORUS AND COORDINATED PYLORIC TTOTILITY IN THE REGULATION OF GASTRIC EMPTYING .