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Module Guide 2005/6 MRes Biomolecular Sciences Basic Mechanisms of Disease MODULE CODE: MODULE LEADERS: SEMESTER: PGY 801 Dr Brian Angus, Dr John Anderson 1 University Department of Pathology, Royal Victoria Infirmary. Module Guide 2005/6 CONTENTS 1. Welcome 2. Introduction and aims 3. Learning outcomes 4. Course presenters 5. Time and place 6. University network support 7. Seminar and practical-demonstration synopsis 8. Practical-demonstrations 9. Assessment 10. Recommended text APPENDIX - LECTURE SUMMARIES Module Guide 2005/6 1. WELCOME Welcome to the module on basic mechanisms of disease. The science of disease is also known as Pathology. We hope you enjoy the course, which is necessarily intense. We appreciate the diverse origins of our students in terms of previous education and experience. It is expected that students undertaking this module will have previously studied biology to GCSE “A” level standard at least. (or related disciplines such as physiology, anatomy or biochemistry to undergraduate degree standard). Your presenters are Pathologists in the Royal Victoria Infirmary. All have a major commitment to microscopic diagnosis of disease as a day-to-day activity and your seminars will reflect this. Please feel free to contribute to seminars and ask questions at all times, and to communicate by e-mail or in person to clarify matters arising from the seminars. Many of you will continue your careers in the Biomedical Sciences and we hope this course serves you well in that endeavour. Let us know what you think at the end of the course. 2. INTRODUCTION AND AIMS Many of the topics covered in other modules relate closely to a wide spectrum of human diseases. This module is intended to provide a basic understanding of each of the classes of human disease covering such aspects as aetiology, actual effects on tissues and result on the individual affected, as well as some coverage on treatment and prevention. Also included in the course is a brief introduction to the ways in which disease is studied and diagnosis made, both before and after death. The course comprises 19 seminars and 7 practical-demonstrations. One practical demonstration is of a human autopsy (optional) whilst the remainder comprise detailed examinations of diseased human tissues. It is intended that these should augment understanding of disease mechanisms and effects as described in the seminars. 3. LEARNING OUTCOMES In order to acquire greatest benefit from the course, students will be expected to undertake a significant amount of supplementary reading. This is because for many students this is an entirely new topic for which very little coverage is given in undergraduate courses. By the end of the module students should have a basic understanding of: a) b) c) d) e) f) g) h) i) Causes of disease, throughout the world, in broad terms (eg vascular, infective) Methods of study and diagnosis of disease How cells are injured and tissues are repaired The processes of acute acute and chronic inflammation Neoplastic disease, both benign and malignant Common vascular diseases Disease caused by immunological mechanisms Examples of diseases of metabolism and homeostasis Trauma, a major cause of human morbidity and mortality Module Guide 2005/6 4.COURSE PRESENTERS Dr. Brian Angus Dr. Fraser Charlton Dr. John Anderson Dr. Nigel Cooper Dr. Chris Wright Dr. Katrina Wood Dr. Judith Bulmer Dr. Sarah Johnson Dr. Shafiq Gill Dr. Marium Khan Mrs. Kirsty Sanderson Module Leader Module leader (joint) [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] [email protected] Course Secretary 5. TIME AND PLACE The course runs on Mondays only over a period of fourteen weeks with two presentations each day commencing at 10.30 am (to be confirmed), with the exception of the autopsy (see timetable). The venue for the presentations will be detailed on the timetable. 6. UNIVERSITY NETWORK SUPPORT Information on the course is posted on Blackboard. Support material is available here at the discretion of individual presenters. You will find announcements on the opening page for the module in Blackboard, and it is suggested that you consult these regularly. Course support material is to be found in the “Course Documents” section in Blackboard. 7. SEMINAR AND PRACTICAL-DEMONSTRATION SYNOPSIS The course is divided into 7 sections: (Note that this is not a timetable, but a guide to content only) 1. INTRODUCTION (i) (ii) (iii) (iv) 2. Introduction to the course Diagnosis of disease and methods of study (Practical-Demonstration) The autopsy (Practical-Demonstration) Causes of disease: genetic and environmental CELL INJURY (i) (ii) (iii) (iv) Cell injury, senescence and death Host response to cell injury (acute inflammation) Host response to cell injury (chronic inflammation and repair) Cell death inflammation and repair (Practical-Demonstration) Module Guide 2005/6 3. NEOPLASIA 1 (i) (ii) (iii) (iv) 4. NEOPLASIA 2 (i) (ii) (iii) (iv) 5. 1a. Basic immunology Hypersensitivity and autoimmune disease Organ transplantation and immunodeficiency Practical-Demonstration METABOLIC AND ENDOCRINE DISEASE, TRAUMA, EVALUATION (i) (ii) (iii) (iv) 8. Atheroma Thrombosis, embolism, ischaemia and infarction Cardiac failure, shock, hypertension Practical-Demonstration IMMUNOLOGICAL DISEASE (i) (ii) (iii) (iv) 7. Carcinogenesis 1. Chemicals, radiation and viruses Carcinogenesis 2. Molecular mechanisms Tumour biology, precursor conditions and screening Practical-Demonstration CARDIOVASCULAR DISEASE (i) (ii) (iii) (iv) 6. Disorders of cell growth Classification of neoplasms Invasion, metastasis, prognostic factors Practical-Demonstration Metabolic disease Endocrine disease Physical injury and trauma Course evaluation PRACTICAL DEMONSTRATIONS Diagnosis of disease and methods of study In a histopathology department of a hospital you will be shown how tissues are processed for diagnosis, and special techniques employed. (this may have to be done this year as a seminar as the Pathology department is currently in a state of flux) 1b. The autopsy In a hospital mortuary, a post mortem will be carried out and findings demonstrated (optional). Module Guide 2005/6 2. Cell injury Various organs affected by inflammatory disease, both acute and chronic, will be studied. 3 & 4. Neoplastic Disease - benign and malignant Examples of common tumours will be presented and discussed. 5 Vascular disease Various tissues including blood vessels affected by disease and organs affected by vascular disease will be studied using preserved specimens of human tissue. 6. Immunopathology A selection of cases (patients with disease) will be presented in the form of illustrated posters. 9. ASSESSMENT In course One essay (3000 words) on specified topics 40% NB As a rough guide, essays should include a minimum of 10-20 references. Deadline Essay: to be set Examination One question to be answered (from choice of 3). 10. RECOMMENDED TEXTS AND PRE MODULE READING LIST The principle recommended text is: General and Systematic pathology 3rd Edition Edited by J C E Underwood Churchill Livingstone Part 1, Part 2 and Chapter 13. Also other parts as indicated by presenters Copies in the Medical School Library 60% Module Guide 2005/6 It is recommended that you refer in brief to the recommended reading material for each seminar before attending the seminar. In addition there may be handouts to download and material to view in Blackboard. Presenters may recommend reading from other books at their discretion. A suitable book for pre module reading is: Pathology: a core text of pathological processes with self assessment. Paul Bass, Norman Carr, Clair du Boulay. Second edition. Churchill Livingstone Module Guide 2005/6 APPENDIX - SEMINAR SUMMARIES 1. INTRODUCTION 1.1 Introduction to the course In this introductory presentation the structure of the course will be described and a brief description of each of the classes of disease covered by the course will be given. Recommended reading: Underwood Chapter 2 2. 1.2 Diagnosis of disease and methods of study (Practical-Demonstration) In a Histopathology Department of a hospital you will be shown how tissues are processed for diagnosis and the special techniques employed. Recommended reading: Underwood Chapter 4 1.3 The autopsy (Practical-Demonstration) In a hospital mortuary, a post-mortem will be carried out and findings demonstrated. You will be located in the viewing area of a mortuary behind a glass screen. The body and the dissection will be visible to you. This should be regarded as an optional part of the course. Recommended reading: Underwood Chapter 4 1.4 Causes of disease: genetic and environmental Most important diseases have an environmental aetiology, for example, infectious disease, but many also have a genetic component such as diabetes mellitus, or are entirely genetic in origin, for example, cystic fibrosis. The seminar will provide an overview of this subject. Recommended reading: Underwood Chapter 3 CELL INJURY 2.1 Cell injury and death Cells and tissues are exposed to many harmful stimuli and respond in a variety of ways, often stereotyped, that permit their continued survival. If survival is not possible, cell death may occur by necrosis or apoptosis. The cellular effects of sub-lethal tissue injury will be described. Necrosis and apoptosis will be compared, with emphasis on the functions and regulation of apoptosis. Recommended reading: Underwood Chapter 6 2.2 Response to Injury I - Acute inflammation Acute inflammation is the body’s response to cellular injury including bacterial infection and necrosis Vascular, fluid and cellular components of the acute inflammatory reaction will be described. Neutrophil polymorphs and monocytes are the major cellular mediators of acute inflammation; their recruitment and major functions will be reviewed. Formation of capillary vessel granulation tissue - the essential link between acute inflammation and the body’s repair processes will be introduced. Recommended reading: Underwood Chapter 10 Module Guide 2005/6 3. 4. 2.3 Response to Injury II - Chronic inflammation and repair When the acute inflammatory response is unable to eliminate an infection or resolve the effects of tissue damage, chronic inflammation often supervenes. In some cases, inflammation has chronic characteristics from the outset, particularly when activation of the immune system is involved in the process. The major cells of chronic inflammation are lymphocytes, which are highly versatile effector cells in inflammation, in addition to their immune functions. The mechanisms of chronic inflammation will be described, including granuloma formation. Repair processes and the resolution of inflammation will be discussed further. Recommended reading: Underwood Chapter 10 2.4 Practical-demonstration Clinical examples of cell and tissue injury, apoptosis and necrosis will be presented. Acute and chronic inflammation will be illustrated, with examples of resolution and healing by scar tissue formation. NEOPLASIA 1 3.1 Disorders of cell growth Following a general introduction about cancer and the commonest types of cancer in this country, the seminar will concentrate on different adaptations of cell growth that occur in response to a change in the cell’s environment. These are atrophy, hypertrophy, hyperplasia, metaplasia and dysplasia. Recommended reading: Underwood Pages 82-88 and 97-99 3.2 Classification of tumours Tumours can be classified by their behaviour and by their cell of origin. The differences between benign and malignant tumours are described and the classification of common tumours explained. Recommended reading: Underwood Pages 224-234 3.3 Invasion, metastasis and prognostic factors Malignant tumours are characterised by their ability to invade and metastasise. These processes are discussed. Prognostic factors in malignant tumours (type, grade and stage) are described and illustrated with a case history. Recommended reading: Underwood Pages 256-262 3.4 Neoplasia 1, Practical-demonstration Clinical examples illustrating the classification of tumours and their clinical behaviour will be demonstrated. NEOPLASIA 2 4.1 Carcinogenesis 1 - Chemicals, radiation and viruses It should be clear to you that genetic changes are responsible for development of neoplasms. These are caused by numerous mechanisms including chemicals such as those in cigarette smoke, ionising radiation, and viruses such as the human papilloma virus. Recommended reading: Underwood Pages 237-247 Module Guide 2005/6 5. 4.2 Carcinogenesis 2 - Molecular mechanisms All our cells contain genes which, when activated by a variety of possible mechanisms, contribute to the neoplastic behaviour of a cell. The mechanisms of activation and the mechanisms of action of oncogenes will be discussed. Some genes act to suppress neoplastic behaviour of the cell; an example is the retinoblastoma gene. When these genes are lost or inactivated, neoplasia can result. The principle of tumour suppressor genes will be discussed and examples of the numerous known tumour suppressor genes provided. Recommended reading: Underwood Pages 249-256 4.3 Tumour biology, precursor conditions and screening In the first part of this presentation the nature of neoplasms will be discussed. Tumour cells are biologically different to their normal counterparts. They often grow more rapidly, fail to respond to signals to undergo apoptosis, and have altered communication with neighbouring cells via alterations in adhesion molecules. Causation of invasive cancer, in many instances, is a multistep process. Some invasive cancers are preceded by a phase where they do not spread into tissues (in-situ disease). Detection at this stage by screening can allow early effective treatment. Recommended reading: Underwood Pages 224-234, 262, 236-237 4.4 Neoplasia 2, Practical-demonstration CARDIOVASCULAR DISEASE 5.1 Atheroma Atheroma and its consequences are the principal cause of morbidity and mortality in Western societies. Lipid rich fibrous plaques build up in the walls of arteries. These plaques can, in themselves, impair blood supply, for example to the heart muscle, when the coronary artery is affected, resulting in angina. Alternatively, atheromatous plaques can develop super-added thrombus and when this occurs in the coronary artery myocardial infarction can result. This is commonly known as a “heart attack”. Recommended reading: Underwood Pages 279-285 5.2 Thrombosis, embolism, ischaemia and infarction Thrombosis is the formation of a semi-solid mass within the vascular system from components of the blood. This is an important disease mechanism. For example, when thrombus forms over an atheromatous plaque in a coronary artery, myocardial infarction (a “heart attack”) will often result. An embolus is a mass of material in the vascular system which is able to become lodged within a vessel and block its lumen. Most of these are composed of thrombus. Important clinical consequences result, for example, when a thrombus forms in the cardiac chambers as a result of myocardial infarction, this may break off and travel in the vascular system, where it can block the blood supply to important organs, such as the brain, resulting in one form of “stroke”. Ischaemia is the condition where there is insufficient blood supply to a part to supply its needs. An example is angina (chest (heart) pain on exertion) where the heart muscle receives insufficient blood due to narrowing of the coronary arteries due to atheroma. Infarction is necrosis (tissue death) due to lack of blood. An example is myocardial infarction due to occlusion of a coronary artery due to thrombosis over an atheromatous plaque. Module Guide 2005/6 Recommended reading: Underwood Pages 149-160 and 301-305 5.3 Cardiac failure, shock, hypertension Heart failure is a major health problem. Inefficient pumping of blood by the heart leads to build up of fluid in the lungs and soft tissues of (e.g.) the legs. The patient cannot breath and is swollen with fluid in the tissues. Shock does not mean extreme and unpleasant surprise in the present context. We will discuss cardiovascular shock, which means sudden failure of the cardiovascular system to supply blood to the tissues. There are many causes. Several million people in the UK are under medication for systemic arterial hypertension (high blood pressure). Why is this? You will find out. Recommended reading: Hypertension: Underwood Pages 288-290 Shock: Underwood Pages 160-162 Cardiac failure: “ Pages 299-301 5.4 6. Vascular disease (Practical-Demonstration) Various tissues, including blood vessels, affected by disease and organs affected by vascular disease will be studied using preserved specimens of human tissue. These will be presented to you as specimens preserved in perspex containers. You will be expected to find and describe the abnormalities present and to decide upon the consequences for the patient. IMMUNOPATHOLOGY 6.1 Basic immunology In order to understand the various mechanisms in which the immune system can be directly involved in disease, an understanding of the humoral and cellular responses of the immune system is required. In this introductory seminar, the contribution of T cells, B cells and immunoglobulin will be described. Recommended reading: Underwood Chapter 9 6.2 Hypersensitivity and autoimmune disease Some types of disease are due to inappropriate or excessive reactivity of the immune system. These are known as hypersensitivity diseases. The most common example is that of allergic asthma in which the body mounts a response to inhaled immunogens which results in the release of factors by mast cells which result in constriction of the bronchi and the typical breathlessness of the asthmatic patient. In autoimmune diseases, the patient develops an immune response to self-antigens. The reason for this is not usually clear. An example is type 1 diabetes mellitus in which the beta cells of the pancreas are destroyed so that insulin is no longer produced. Recommended reading: Underwood Chapter 9 6.3 Organ transplantation and immunodeficiency When organs are transplanted from one human to another, the natural result is rejection of the organ by the immune system. However, this can be overcome by HLA matching and by suppression of the immune system. This is now an important area of medicine in western society. Module Guide 2005/6 Congenital immunodeficiency is rare and takes many forms and these diseases will be briefly discussed. Of greater importance in general terms are the acquired immunodeficiencies. This includes those generated by doctors treating patients with drugs which suppress the immune system in the context of organ transplantation or treatment of malignant disease and also HIV infection. Recommended reading: Underwood Chapter 9 6.4 7. Immunopathology (Practical-Demonstration) A selection of cases (patients with particular diseases) will be presented in the form of illustrated posters. Tutors will be on hand to discuss their cases with you and to ensure that you understand the basic disease processes illustrated. METABOLIC, ENDOCRINE, PHYSICAL INJURY 7.1 Disorders of metabolism This is a wide subject and only examples will be given. In particular, diabetes mellitus will be discussed. In this disorder, there is either a lack of insulin or a lack of response to insulin in the body, giving rise to a high blood sugar. The different types of diabetes and the effects upon the body will be described. Recommended reading: Underwood Chapter 7 7.2 Endocrine disease The endocrine system is a major body communication system. The various endocrine glands secrete hormones which travel in the blood and interact with receptors in other glands or tissues. For example, the pituitary gland secretes growth hormone which is necessary for growth at puberty. Over or underactivity of the various endocrine glands results in a number of common conditions. Diabetes is the most important of these but is discussed in the previous lecture. Recommended reading: Underwood Chapter 17 7.3 Pathology of trauma It is very easy to forget that the large amount of morbidity and mortality, particularly amongst the younger sections of our society, results from trauma. This of course is mainly as a result of road traffic accidents in the UK. This subject cannot be omitted in any course describing basic mechanisms of disease. The effects of trauma upon the human body, for example, the syndrome of shock following blood loss, will be described with numerous illustrative examples. 7.4 Course appraisal Your views on the course, positive and negative, will be invited firstly by discussion and then by anonymous questionnaire with opportunity for free text comment. This appraisal is to enable the module leader to improve the course for next year, and also represents one facet of audit of module quality.l.