University of Leeds School of Medicine
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CONTENTS Aims & Objectives Module team Outline syllabus Learning outcomes Assessments Teaching & learning Lectures Practicals Case studies Self directed Resources Textbooks Websites Related ICUs Evaluation Timetable

Oesophageo-gastric junction

Gastrointestinal diseases are common in clinical practice^¶, and their effective diagnosis and treatment requires a thorough understanding of the normal function of the digestive tract. Eating disorders are a significant source of ill-health and diabetes mellitus is the most common endocrine disease. Nutritional factors have a major impact on pathological processes in other body systems, and an appreciation of the absorbtion, distribution and elimination of common drugs is an essential pre-requisite for clinical practice. This unit aims to

• develop an understanding of digestion, absorption, storage and utilisation of food in health and disease
• promote enquiry into the relationships between diet, lifestyle, health and disease
• consider how drugs and other substances are absorbed into, distributed and excreted from the body

[^¶Health Statistics for the USA have been published by the National Institute for Diabetes, Digestive and Kidney Diseases (NIDDK) and analysed in terms of diabetes and obesity. The incidence of gastrointestinal disease in the United Kingdom broadly resembles the North American pattern, although the statistics were collected on a different basis. The annual cost of GI complaints in the UK has been estimated as £8 billion, or 1.3% of GDP.]

Broad Objectives

By the end of the unit the student will

• understand the development, structure and normal working of the gastro-intestinal (GI) tract, and related organs, as an integrated semi-autonomous system
• understand the basic principles of human nutrition, and appreciate how diet can influence health and disease.
• be aware of some common diseases affecting the GI tract, and the scientific basis for their treatment using surgery or drugs.
• understand how food intake and storage are normally co-ordinated with metabolic needs, and how diseases may disturb this process.
• understand (at an elementary level) how various chronic diseases cause disturbances of the energy balance, and how these respond to therapeutic intervention.

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ICU Team

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Pre-requisite Knowledge

• A basic knowledge of biology and chemistry
• Elementary computer literacy

Outline Syllabus

• Overview of the system as a whole - embryology, structure and function; integrated response to eating, digestion and metabolism; interactions between the major metabolic regulatory systems; the role of the GI tract in immune responses; major and minor constituents of food, diet, food values and nutritional requirements: parenteral nutrition; nutrition through the life cycle.
• Understanding upper GI function - salivation, chewing, swallowing, dysphagia; gastric structure and function; local gut reflexes and hormonal signalling systems; satiation; vomiting; helicobacterium pylori; principles of drug treatment of gastric and oesophageal complaints.
• Understanding absorption - principles underlying normal function, malnutrition, malabsorption and food intolerance - anatomy, histology and ultrastructure of pancreas and small intestine; emulsification and hydrolysis of foodstuffs; local nervous system and hormonal signalling; uptake and enterocyte processing of sugars, amino-acids, minerals, vitamins and fats; enterohepatic circulation of cholesterol and bile acids; common causes and nutritional consequences of malabsorption; inflammatory bowel disease.
• Liver function including drug metabolism - hepatic and biliary anatomy, histology and ultrastructure; metabolic and control function of the liver; common hepatobiliary disorders (jaundice and hepatitis); role of the liver in drug metabolism; metabolic and social effects of alcohol and drug abuse.
• Exercise and food utilisation - basic endocrinology in relation to normal nutrition and metabolism; integrated response to stress; effects of insulin, corticosteroids, glucagon and catecholamines; specialised metabolism in muscle and adipose tissue cells; metabolic effects of exercise and physical activity; blood glucose homeostasis; dietary effects and implications of type 1 and type 2 diabetes;
• Obesity and eating disorders - lipid metabolism; leptin; eating behaviour; eating disorders; social factors affecting physical activity and diet; physiological and metabolic responses to stress such as cold, infection, trauma and psychological insults.
• Bowel function: anatomy and histology of the large intestine; gut transit times; change in bowel habit, diarrhoea, constipation; drug action; colorectal cancer

At the end of the unit the student will be able to:

• Describe the growth and development of the gastro-intestinal tract, the detailed anatomy in the adult, and the most common inherited and acquired defects.
• Describe the physiological and biochemical processes, including the nervous and hormonal signals, required for the normal digestion and absorption of food, and the movement of the gastro-intestinal contents.
• Understand (at an elementary level) the epidemiology, pathogenesis and treatment of the most common gastro-intestinal diseases.
• Describe the various components of a healthy diet, indicating their principal physiological and biochemical functions, and the pathological consequences observed in deficiency states.
• Recognise the social factors influencing food choice,and the importance of diet in government policy, e.g ‘Healthy Weight, Healthy Lives; A Cross Government Strategy for England’
• Describe the biochemical and physiological processes involved in the transport of nutrients from the gut, their storage in liver, muscle and adipose tissue, and in their mobilisation and distribution to other parts of the body in times of need.
• Understand the importance of sub-cellular and inter-organ compartmentation in metabolism, and the metabolic specialisation observed in differentiated tissues.
• Explain how blood glucose concentration is regulated in healthy individuals, and how this process is disturbed in type 1 and type 2 diabetes mellitus.
• Explain how appetite, body weight and nitrogen balance are regulated in healthy individuals. Outline the effects of stress, neoplasia, renal disease, parasitism, sepsis and surgical trauma. Describe the medical consequences of inadequate and excessive food intakes.
• Outline the metabolism of alcohol and commonly-used drugs, and account for the most obvious effects of these compounds on human nutrition.

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In Course Assessments

Formative Assessment

Assessment of this ICU consists of 3 elements:

The Shuttleworth Prize (£30) will be awarded to the student who obtains the highest mark in the Spot Test.

The Spot Test must be passed in its own right, but standard compensation will be applied across the other 2 elements of assessment, i.e. one E grade may be compensated by C grade or above in the other assessment. Students must pass both components (Spot Test & written/preparatory work) to pass the course.

Anatomy Spot Test: Friday 20 August

Students who fail the written element of assessment will be set assignments (individualised according to student performance) to be completed by Monday 17 August.

Model answers, and self-assessment EMQ tests will be provided through the module website.

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Teaching and Learning

Lecture Synopses

Lecture 1: Chewing, tasting and swallowing. (Dr Roberts) The anatomy of chewing, tasting and swallowing. This is an e-lecture, available via the VLE.

Lecture 2: Peritoneal reflections. (Dr McConnell) Arrangement of the gut tube and associated organs within the abdominal cavity. Disposition of the peritoneal membrance to form the mesenteries and omenta, the greater and lesser sacs and the supracolic and infracolic compartments. Clinical significance of this arrangement

Lecture 3: Motility. (Dr Hunter) The unitary nature of the smooth muscle of the GIT and the role of the nexi in the transmission of the electrical signal between cells; slow wave electrical activity, spike activity and contractile activity; receptive-relaxation; vago-vagal reflexes; enterogastric reflex and "enterogastrone"; peristalsis and segmentation; migrating motor complex; peristalsis, haustral shuffling and mass propulsive movements in the colon; the defaecation reflex, initiation, sampling and the control of external and internal sphincters

Lecture 4: Regulation. (Dr Hunter) Endocrine, paracrine and neurocrine secretion; criteria which should be met before a hormone can be assumed to be involved in regulation of the GIT in vivo; sites of synthesis and release of the major hormones gastrin, secretin, CCK-PZ GIP; the primary secretagogues of the major hormones and the actions of the hormones on the target tissues; the biochemical division of the hormones into the two families, gastrin-like and secretin-like hormones; the terminal amino acid sequence of gastrin and CCK-PZ which is responsible for the shared actions of these hormones; the distinction between the extrinsic and intrinsic nerve supplies to the GIT; the origins of the extrinsic nerves; the major effects of stimulation of the nerves on the GIT (e.g. motility, salivary, gastric and pancreatic secretions.

Clinical Session: Overview of the GI tract and its diseases (Dr Donnellan)

Lecture 5 & 7: Immunology of the gut (2 lectures) (Dr Taylor-Robinson) An overview of the cellular organisation of the gut immune system, how it responds to antigen challenge, and the diseases that affect it.

Lecture 6 & 8: Secretion (2 lectures) (Dr Hunter) Sympathetic or parasympathetic stimulation; composition and cellular origin of the various components; the two-stage hypothesis of salivary secretion; the cellular basis of acid secretion; active K+/H+-exchange; the protective bicarbonate/mucus barrier mechanism; induction and prevention of ulceration; control of gastric acid sectretion (cephalic, gastric and intestinal); components of pancreatic secretion (enzymes and electrolytes); reciprocal relationship between the concentration of bicarbonate and chloride in pancreatic juice and flow rate-dependence; cephalic, gastric and intestinal phases of control; the life-cycle of enterocytes; c-AMP and secretory diarrhoea of cholera

Clinical Session: How patients are fed artificially (Dr Donnellan) Nutritional requirements and nutritional assessment. Artificial nutrition - reasons, routes, feed composition, monitoring, and complications.

Lectures 9 & 11: Digestion and absorption (2 lectures) (Dr Hunter) Elementary chemical structures of the main dietary foodstuffs (carbohydrates, fats and proteins) and their breakdown by digestive enzymes; sources of the digestive enzymes, secreted and brush border; mechanisms of absorption; coupled transport of monosaccharides and amino acids with sodium; facilitated diffusion of some monosaccharides; passive diffusion of monoglycerides, fatty acids and D-amino acids; emulsification and micelle formation in the duodenal lumen; unidirectional secretory and absorptive fluxes; calcium, iron and vitamin B12 handling; colon electrolyte handling and modulation by mineralocorticoids

Clinical Session: Nutrition in renal disease (Dr M Wright) The talk will discuss the high prevalence of malnutrition in patients with renal failure and examine the underlying reasons. There will be particular focus on the mechanisms that reduce nutrient intake and the metabolic problems that lead to abnormal processing of nutrients in these patients.

Lecture 10: Development of the GI tract [1]. (Dr Nunn) Formation of primitive gut tube. Formation of vitelline duct. Blood supply to the gastrointestinal tract. Formation of the oesophagus and oesophageal abnormalities including Barrett’s oesophagus and short oesophagus. Embryology of the stomach including its histogenesis and congenital pyloric stenosis. Modification of the primitive dorsal and ventral mesenteries.

Lecture 12: Development of the GI tract [2]. (Dr Nunn) Development of the midgut. Fixation of the intestines. Histological development of the small intestine. Embryological abnormalities including omphalocoele, gastrochisis, congenital umbilical hernia, non-rotation of the midgut, midgut rotation and volvulus. Hindgut development.

Lecture 13: Development of the GI tract [3] (Dr Nunn) Glands of the digestive tract. Formation of the liver and biliary apparatus. Functions of the developing liver. Biliary atresia and variations in the cystic artery. Formation of the pancreas at the gross and histological level. Ectopic and annular pancreas; formation and consequences.

Lecture 14: Introduction to metabolism (Dr Illingworth)

Lecture 15: Structure and functions of the liver. (Dr Whittle) The anatomical and cellular structure of the liver. An overview of liver function, and its role in bile formation, xenobiotic detoxification and haem breakdown.

Lecture 16: Post-absorption processing of carbohydrates. (Dr Whittle) The possible fates of carbohydrates after absorption. Glycolysis, glycogen synthesis and breakdown, fatty acid and triglyceride synthesis.

Lecture 17: Post-absorption processing of dietary lipids. (Dr Whittle) Transport of lipids, fate of lipids in peripheral tissue. Cholesterol and its role in atherosclerosis.

Clinical Session: Malabsorption (Dr Heatley) Main causes of malabsorption including coeliac disease, inflammatory bowel disease, pancreatic and liver disease. Main effects of malabsorption, e.g. anaemia, steatorrhoea, osteomalacia. Symptoms and signs of malabsorption, treatment.

Clinical Session: Obesity (Prof Hill, Dr Barth, Ms O’Kane) The recent increase in prevalence of obesity and reasons underlying this. The main approaches to obesity treatment. The dietetic approach to managing adult obesity.

Lecture 18: Post-absorption processing of dietary nitrogen. (Dr Whittle) Amino acid metabolism. Ureogenesis. Role of proteins in energy metabolism and as substrates for gluconeogenesis.

Clinical Session: Cystic fibrosis, a personal perspective (Lynsey Morton, Cystic Fibrosis Trust)

Clinical Session: Liver disease (Dr Aldersley) Normal structure and function of liver and biliary system. Principal pathological states, - acute inflammation (e.g. hepatitis), chronic disease (e.g. cirrhosis) and biliary obstruction - causes, signs and symptoms, and treatment options.

Lecture 19: Bioenergetics [1] - substrate oxidation. (Dr Illingworth) Sub-cellular compartments and the final common pathways for substrate oxidation via the citric acid cycle and the mitochondrial respiratory chain.

Lecture 20: Bioenergetics [2] - ATP synthesis. (Dr Illingworth) Proton gradients, oxidative phosphorylation, creatine phosphate and the subcellular transport of ATP.

Lecture 21: Pancreatic islets, release of insulin and its effects. (Dr Illingworth) Specialised metabolism in pancreatic b cells and the role of ATP in the regulation of insulin release. Oral hypoglycaemic agents. Insulin receptors. Immediate effects of insulin on glucose transport and enzyme activity, and its long-term effects on gene expression.

Lecture 22: Specialised metabolism of differentiated tissues. (Dr Illingworth) Metabolic differences between liver, muscle, adipose tissue and brain. Signalling and cooperation between tissues. Tissue differences in receptors and hormonal responses.

Lecture 23: Mobilisation of food reserves [1] - catecholamines & glucagon. (Dr Illingworth) Glycogen phosphorylase and mobilising lipase. Signal amplification by enzyme cascades. a and b-receptors, calcium movements, calmodulin, adenyl cyclase, protein kinases and cyclic AMP.

Clinical Session: Eating Disorders (Professor Hill) This will include a description of the main types of eating disorders, perspectives on their development, and an overview of their prevalence, characteristics and treatment. Details of resources for further information and assistance will also be provided.

Lecture 24: Mobilisation of food reserves [2] - ACTH & steroid hormones. (Dr Illingworth) Hypothalamic releasing factors, pituitary and adrenal cortex. Metabolic and physiological effects of corticosteroids and growth hormone on energy supply.

Lecture 25: Thyroid hormones, thermoregulation and basal metabolic rate. (Dr Illingworth) Roles of hypothalamus, pituitary and thyroid gland in regulating basal metabolic rate. Effects of thyroid hormones on gene expression and metabolism. Clinical and behavioural effects of abnormal thyroid function.

Lecture 26: Eating disorders, leptin, NPY and regulation of body weight. (Dr Illingworth) Feedback systems which normally coordinate food input with energy expenditure, and what happens when these go wrong.

Clinical Session: Diabetes (Dr Ajjan) The manifestations and recognition of diabetes - management and complications

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Small Group Teaching

Anatomy Classes: (22 groups of ~6 students). Each class will last for 2 hours, and will be given twice, half the students attending on each occasion.

Class 1: Anatomy of the peritoneal cavity

Class 2: Stomach and structures supplied by superior mesenteric artery

Class 3: Liver and structures supplied by inferior mesenteric artery

Class 4: Duodenum, pancreas and spleen

Computer assignment: Medical Imaging Cross-sectional anatomy, MRI, CT. This session aims to augment and consolidate the dissection sessions. Students will complete a paper workbook using images from the computer network.

Anatomy tutorials: Revision/consolidation tutorials will be provided after Class 2 and Class 4.

Radiology/Living anatomy sessions: the radiology session will use plain films, CT (computed tomography) and MRI (magnetic resonance) images to enable students to integrate the knowledge learned in dissection to radiological imaging. The session will be led by a Radiologist and will focus on anatomy of the GI tract.

Work Sessions: Each session lasts for 2 - 3 hours.These classes may include a short video in the Medical Lecture Theatre associated with the topics. These videos will be shown once only; all students should attend, regardless of the day they are assigned to the work session. There will be preparation and / or follow-up work associated with each topic, and completion of these assignments is an integral part of the course.

Most work sessions will be taught in groups of approximately 30 students, with 2 demonstrators per group. Work sessions 3 and 6 will have a taught and a self-directed component. The taught session will be in groups of around 12, with a biochemistry tutor.

Session 1 :Peptic ulcers and related topics This study examines the underlying scientific basis for the most common causes of peptic ulceration, and their treatment.

Session 2:Students' diets: Students will collect data on their own lifestyle and diets before the class commences. The practical compares individual nutrition with national guidelines, developing concepts of normal range and the great variety of "normal" behaviour.

Session 3:Lower GI tract This session revisits the physiological functions of the large bowel, in the context inflammatory bowel disease, diverticular disease and psychiatric problems. It also considers the immunology associated with some disorders of the digestive tract.

Session 4: Malabsorption & ion channels This session draws together common principles from the pathology and treatment of cholera, cystic fibrosis, lactose intolerance and gluten intolerance.

Session 5: Alcohol addiction and related topics This examines the biochemistry and pathology of alcohol dependency.

Session 6: Obesity This session deals with issues including measuring overweight and obesity, associated health problems, understanding energy balance and applying this to changing eating and increasing physical exercise. This work session is followed by a seminar given by people with research and clinical expertise in obesity. The focus will be on the prevalence and costs of obesity in the UK and the management of obesity within and outside the NHS.

Session 7: Human energy metabolism This class revisits some of the difficult scientific concepts from the lecture course, in the context of muscle activity and mitochondrial function.

Session 8: Liver and pancreas This session examines the exocrine functions of the liver and pancreas.

Session 9: Endocrine diseases This session examines the consequences of the over- or under-activity of endocrine glands.

Session 10: Diabetes A work session that examines the integration and coordination of energy metabolism, illustrated by case studies and worksheets on diabetes mellitus (type 1 and type 2).

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Self-directed learning

Self-directed learning

You are expected to spend around 10 hours a week on self-directed learning associated with this course. This should include:

• Additional reading and reviewing lecture notes
• Preparation for and completion of work sessions
• Completion of the histology workbook
• In course assessments
• Completion of drug profiles for the drugs covered in this ICU

Students are expected to complete the preparation tasks for the Work Sessions in advance, and to bring appropriate text books to these sessions. This preparation forms part of the in course assessment. For the tutor-led classes ALL the questions should be prepared in advance, since there will be only limited time for discussion during each session.

Total hours and student contact time

Total hours: 23 x 7 hour days = 161 hours (allowing for Bank Holidays), made up as follows: lectures: 25 x 1 hours; Clinical Sessions 8 x 1 hour; BMS practicals: 4 x 2 hours; cross sectional anatomy 2 hours; Work Sessions: 24 hours self-directed learning: 95 hours; total staff contact time: 67 hours.

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Resources

Reading List

Recommended texts that you should consider purchasing (or may already own):

• Berne & Levy Physiology 5th Edn., Mosby 2005
• Kumar & Clark Clinical Medicine Saunders 2005 Note that this text is available on-line
• Sadler Langman's Medical Embryology 7th edn., Saunders 1998
• Smith, Marks & Lieberman Marks' Basic Medical Biochemistry: A Clinical Approach Williams & Wilkins, Baltimore 2005
• Young, Lowe, Stevens & Heath Wheater's Functional Histology 5th edn. Churchill Livingstone; 2006

Other textbooks, available from the library, which you may find useful for particular aspects of the course

• Anderson et al. Mosby's Medical, Nursing & Allied Health Dictionary 6th edn., Mosby Year Book Inc; 2002.
• Geissler, C. & Powers, H. Human Nutrition,11th Edn. Edinburgh: Elsevier, 2005
• Golan, Tashjian, Armstrong & Armstrong Principles of Pharmacology 2nd Edn Lippincott, Williams & Wilkins 2008
• Johnson Gastrointestinal Physiology 6th edn. 2001
• Lodish et al. Molecular Cell Biology 5th edn., W.H. Freeman; 2004
• Lydyard, Whelan & Fanger Instant Notes in Immunology 2nd edn, BIOS Scientific Publishers 2004
• Nelson & Cox Lehninger Principles of Biochemistry 4th edn. Worth; 2005
• Nightingale JMD (Ed) Intestinal failure Greenwich Medical Media 2001
• Parham, P The Immune System 2nd edn. Garland Publishing 2005
• Payne-James, Grimble, & Silk ( Eds.) Artificial Nutrition Support in Clinical Practice 2nd edition, Oxford University Press 2000.
• Rang, Dale, Ritter & Moore Pharmacology 5th edn. Churchill Livingstone; 2003
• Strachan & Read Human Molecular Genetics 3rd edn., BIOS Scientific Publishers; 2004.

The "Nutrition in Medicine" interactive CDs published by the University of North Carolina are also available via the counter collection in the Health Sciences Library. These titles currently include:

• Nutritional Anemias v3.0 (2000)
• Nutrition and Stress
• Nutrition and Cancer (1999)
• Diet, Obesity and Cardiovascular Disease
• Diabetes and Weight Management v3.0 (2000)
• Maternal and Infant Nutrition
• Nutrition and Growth v3.5 (2000)
• Nutrition for the Second Half of Life
• Supplements and Fortified Foods awaiting cataloguing
• Sports Nutrition

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Websites

In addition to new materials produced specifically for this module, this unit exploits high-quality teaching resources available via the Internet. These sites include:

• American Diabetes Association
• American Gastroenterological Association
• British Society of Gastroenterology
• CORE
• Medscape
• National Institute for Diabetes, Digestive and Kidney Diseases
• Online Mendelian Inheritance in Man
• Bandolier
• Animations based on Immunobiology textbook
• Labelled Cross Sections
• Embryology materials
• histology slides for self testing from Boston University
• histology slides for self testing from University of Wisconsin
• Association for the Study of Obesity
• A pharmacology database which covers basic clinical conditions and their treatment, together with self test material
• Instant Anatomy - a website to aid the learning of human anatomy
• University of Western Australia histology site - images and quizzes
• MSRC site has a wide range of links to useful internet resources

These sites provide a wide range of material which will be of value to you for self-directed learning, both for this course, and in the future.You are not expected to visit them all, or exhaustively review their contents

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Links with other ICUs

• Control and Movement
  pituitary function
  calcium metabolism
  
  
• Individuals and Populations
  Eating disorders
  obesity
  alcohol dependence
  chronic illness
  
  
• Patient Evaluation
  clinical aspects of GI, endocrine and metabolic disease
  
  
• Biomedical Sciences
  enzymes
  cell signalling
  membrane structure and function

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Evaluation of the Course

The following techniques will be used to monitor the course:

• student feedback sessions with the course manager
• student feedback questionnaires
• student feedback discussion groups
• course management team meetings including student representation

Evaluation will be based on:

• student and staff feedback
• peer review of teaching
• student performance in formative and summative assessments
• External Examiner comment

External Examiners will be asked to comment on course documentation during the on-going development process

Responses to student feedback

As a result of feedback received and the Quality Management Review, the following Action Plan for 2008/9 has been agreed to ensure that changes and improvements to the delivery of teaching are maintained. Feedback on last year’s course was generally very positive; alterations to course materials and organisation made in response to feedback are detailed below.

• The histology workbook will be revised
• Two anatomy revision tutorials will be introduced, to help ensure that students have the correct information, and have an opportunity to deal with difficult topics.
• Lectures will be reorganised so that Dr McConnell’s lecture is placed first.
• The lectures which received poor feedback will be reviewed, and feedback monitored.

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