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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.