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Edited by J C E Underwood
Preface
This new textbook, intended primarily for medical students, presents pathology in the
context of modern medicine and cellular biology.
We have adopted the long-established practice of dealing with general pathology (the
principles of disease processes) before covering systematic pathology (specific diseases
affecting individual body systems or organs). Each chapter in the systematic section begins
with a brief account of the relevant normal structure and function of the organ or system,
emphasising those aspects which are pertinent to a proper understanding of its pathology.
After each major heading within a chapter, where it is considered appropriate, there is a
summary panel listing key facts; these have two purposes: first, to provide the reader with a
foundation of basic knowledge on which the subsequent details can be placed; second, to
assist revision by scanning the text. Where relevant, there are brief comments on treatment
and its relationship to the pathological features of a disease. Each chapter ends with a list of
references to review articles or specialist texts for further reading.
Although pathology extends into the realm of molecular abnormalities, much of it has
a visible expression. Illustrations are, therefore, essential. This book contains numerous colour
illustrations of diseased tissues at a gross or microscopic level. The morbid images of disease
also, in a modern textbook of pathology, should include radiographs, computerised
tomography (CT) scans, and magnetic resonance images (MRI); these have been used when
relevant. Clear drawings are used to depict important mechanisms or principles.
The book ends with a glossary of words used frequently in pathology, but which, by
usage, have a meaning slightly different from that to be found in most dictionaries or in the
public domain.
All chapters have been carefully reviewed by expert independent advisers and
invariably edited in line with their recommendations. However, no new textbook could claim
to be perfect. I hope that subsequent editions will benefit from comments received from
medical students and their teachers.
Sheffield JCEU
1992
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Chapter 1: Introduction to pathology
Pathology is the scientific study of disease. In clinical practice and medical education,
pathology also has a wider meaning: pathology constitutes a large body of scientific
knowledge, ideas and investigative methods essential for the understanding and practice of
modern medicine.
History of pathology
The evolution of concepts about the causes and nature of human disease reflects the
prevailing ideas about the explanation for all worldly events and the techniques available for
their investigation. Thus, the early dominance of animism, in the philosophies of Plato and
Pythagoras, resulted in the attribution of disease to the adverse influences of immaterial or
supernatural forces; it was therefore assumed that nothing could be learnt from the objective
examination of the corpses of those who succumbed. Even when the clinical significance of
many abnormal physical signs was established early in the long history of medicine, the
natture of the underlying disease was thought to be due to an excess or deficiency of the
various humours - phlegm, black bile, and so on. These concepts are now firmly and
irrevocably consigned to medical antiquity.
The first opportunity for the scientific study of disease came from the interanl
examination of the body after death. Autopsies (necropsies or post-mortem examinations) have
been performed scientifically from about 1500 AD and have revealed much information that
has helped to clarify the nature of many diseases. As these examinations were confined
initially to the gross (rather than microscopic) examination of the organs, this period is
regarded as the era of morbid anatomy. During the 19th century in Germany, major
contributions were made by Rokitansky and Aschoff, who meticulously performed and
documented many thousand of autopsies and correlated their findings with the clinical signs
and symptoms of the patients and with the natural history of a wide variety of diseases.
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Rudolf Virchow (1821-1902), a German pathologist and ardent advocate of the
microscope, recognised that the cell was the smallest viable constituent unit of the body and
contrived a new and lasting set of ideas about disease - cellular pathology. The light
microscope enabled him to see changes in diseased tissues at a cellular level and his
observations have had a profound influence. That does not mean to say that Virchow's cell
pathology theory is immutable. Indeed, current advances in biochemistry are revolutionising
our understanding of many diseases at a molecular level; we now have biochemical
explanations for many of the cellular and clinical manifestations of disease.
The impact of molecular pathology is exemplified by the advances being made in our
knowledge of the biochemical basis of congenital disorders and cancer. Techniques with
relatively simple principles (less easy in practice) can reveal the change of a single nucleotide
in genomic DNA resulting in the synthesis of the defective gene product that may be the
fundamental lesion in a particular disease.
Pathology is the foundation of medical science and practice. Without pathology, the
practice of medicine would be reduced to myths and folklore. Pathology is, therefore, an
integral part of modern medicine.
Clinical pathology
Experimental pathology
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Subdivisions of pathology
- microbiology: the study of infectious diseases and the organisms responsible for them
- chemical pathology: the study and diagnosis of disease from the chemical changes
in tissues and fluids
These subdivisions are more important professionally (because each requires its own
team of specialists) than educationally. The subject must be taught and learnt in an integrated
manner, for the body and its diseases make no distinction between these conventional
subdivisions.
Techniques of pathology
Our knowledge of the nature and causation of disease hase been disclosed by the
continuing application of technology to its study. Before microscopy was applied to medical
problems (c 1800), observations were confined to those made with the unaided eye, and thus
was accumulated much of our knowledge of the morbid anatomy of disease.
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Light microscopy
If solid tissues are to be examined by light microscopy, the sample must first be thinly
sectioned to permit the transmission of light and to minimise the superimposition of tissue
components. These sections are routinely cut from tissue hardened by permeation with and
embedding in wax or, less often, transparent plastic. For some purposes (eg, histochemistry,
very urgen diagnosis) sections have to be cut from tissue that has been hardened rapidly by
freezing. The sections are stained to help distinguish between different components of the
tissue (eg, nuclei, cytoplasm, collagen).
Histochemistry
Electron microscopy
Electron microscopy has extended the range of pathology to the study of disorders at
an organelle level, and to the demonstration of viruses in tissue samples from some diseases.
Biochemical techniques
Biochemical techniques applied to the body's tissues and fluids in health and disease
are now one of the dominant influences on our growing knowledge of pathological processes.
The clinical role of biochemistry is exemplified by the importance of monitoring fluid and
electrolyte homeostasis in many disorders. Serum enzyme assays are used to assess the
integrity and vitality of various tissues; for example, raised levels of cardiac enzymes in the
blood indicate damage to cardiac myocytes.
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Haematological techniques
Haematological techniques are used in the diagnosis and study of blood disorders.
These techniques range from relatively simple cell counting, which can be performed
electronically, to assays of blood coagulation factors.
Cell cultures
Cell cultures are widely used in research and diagnosis. They are an attractive medium
for research because of the ease with which the cellular environment can be modified adn the
responses to it monitored. Diagnostically, cell cultures are used to prepare chromosome
spreads for cytogenetic analysis.
Medical microbiology
Molecular pathology
Many advances are now coming from the relatively new science of molecular
pathology, defects in the chemical structure of molecules arising from errors in the genome,
the sequence of bases that directs amino acid synthesis. Using in situ hybridisation it is
possible to render the presence of specific genes or their messenger RNA visible in tissue
sections or cell preparations. Molecular pathology is manifested in various conditions, for
example: abnormal haemoglobin molecules, such as in sickle cell disease (Ch 22); abnormal
collagen molecules in osteogenesis imperfecta (Ch 5); and alterations in the genome
governing the control of cell and tissue growth, now believed to play an important part in the
development of tumours (Ch 9).
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General pathology
These processes are covered in Part 1 of this textbook and many specific diseases
mentioned by way of illustration. It is essential that the principles of general pathology are
understood before an attempt is made to study systematic pathology. General pathology is the
foundation of knowledge that has to be laid down before one can begin to study the
systematic pathology of specific diseases.
Systemic pathology
Learning pathology
There are two apparent difficulties that face the new student of pathology: language
and process. Pathology, like most branches of science and medicine, has its own vocabulary
of special terms: these need to be learnt and understood not just because they are the language
of pathology; they are also a major part of the language of clinical medicine. The student
must not confuse the learning of the language with the learning of the mechanisms of disease
and their effects on individual organs and patients. For example, the term 'hyperplasia' means
an increase in the size of an organ due to the proliferation of its constituent cells; this
definition must be learnt before the student attempts to learn about the process of hyperplasia.
In this book, each important term will be clearly defined in the main text or the glossary or
both.
A logical and orderly way of thinking about disease and their characteristics must be
cultivated; for each entity the student should be able to run through the list of chief
characteristics that apply to any disease:
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- incidence
- aetiology
- pathogenesis
- pathological and clinical features
- complications and sequelae
- prognosis (see Ch 2).
Our knowledge about many diseases is still incomplete, but at least such a list will
serve to prompt the memory and enable students to organise their knowledge.
Pathology is learnt through a variety of media; in addition to this textbook the student
will no doubt have a fairly comprehensive course of relatively didactic lectures perhaps
supplemented by tutorials, problem-solving-orientated practical classes involving the fross and
microscopic examination of diseased tissues, demonstrations, and post-mortem teaching. If a
student's curriculum lacks one or more of these features it should not be considered in any
way deficient because there is no prescribed way of teaching the subject and each medical
school will have evolved its own scheme based on local factors. Nevertheless, students of
pathology should be encouraged to avail themselves of every opportunity to learn about
diseases through a variety of media. Even the bedside, operating theatre and outpatient clinic
provide ample opportunities for further experience of pathology; hearing a diastole cardiac
murmur through a stethoscope should prompt the listening student to consider the pathological
features of the narrowed mitral valve orifice (mitral stenosis) responsible for the murmur, and
the effects of this stenosis on the lungs and the rest of the cardiovascular system.
Clinicopathological integration
Although medicine, surgery, pathology and other disciplines are frequently taught as
separate subjects in the curriculum, students must develop an integrated understanding of
disease. Diseases are compartmentalised in this way only so that all aspects can be taught in
sufficient depth to provide a full and working understanding. In practice, no such boundaries
exist.
- problem-oriented
- disease-oriented.
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The problem-orientated approach
The problem-orientated approach is still the first step in the clinical diagnosis of
disease. In many illnesses, symptoms alone suffice for diagnosis. In other illnesses, the
diagnosis has to be supported by clinical signs (eg, abnormal heart sounds). In some instances,
the diagnosis can be made conclusively only by special investigations (eg, laboratory analysis
of blood or tissue samples, imaging techniques).
The disease-orientated approach has also proved to be the most successful manner in
which to impart pathological knowledge. It would be possible to compose a textbook of
pathology in which the chapters were entitled, for example, 'Cough', 'Weight loss', 'Headaches'
and 'Pain' (these being problems), but the reader would be unlikely to come away with a clear
understanding of the diseases. This is because one disease may cause a variety of problems -
for example, cough, weight loss, headaches and pain - and may therefore crop up in several
chapters. Consequently, this textbook, like most textbooks of pathology (and, indeed, of
medicine) adopts a disease-orientated approach.
Making diagnoses
Having carried out this process in an individual patient, proof or strong suspicion of
a particular disease eventually emerges as the diagnosis. If the diagnosis is still uncertain, a
pragmatic approach to the problemmm can be adopted by observing the effects of a specific
treatment or some other intervention.
Although experienced clinicians can diagnose many patients' diseases quite rapidly
(and possibly reliably), the student will find that it is helpful to adopt a formal strategy based
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on a series of logical steps leading to the gradual exclusion of various possibilities and the
emergence of a single diagnosis. For example:
- First decide which organ or body system is likely to be affected by the disease.
- From the signs and symptoms, decide which general category of disease
(inflammation, tumours, etc) is likely to be present.
- Then, using other factors (age, gender, previous medical history, etc), compute a
diagnosis or a small number of possibilities for investigation.
- Investigations should be performed only if the outcome of each one can be expected
to resolve the diagnosis, or influence management if the diagnosis is already known.
This strategy can be refined and presented in the form of decision trees or diagnostic
algorithm, but these details are outside the scope of this book.
Diagnostic pathology
Biopsies are samples of tissue removed from a patient for diagnostic purposes.
Resection specimens (eg, gastrectomies, thyroidectomies) are the whole or part of an organ
removed for a previously diagnosed condition. In addition to their diagnostic utility, much is
being learned about the pathology of many diseases from the study of these tissue samples.
- incisional biopsy: tissue removed by surgical incision (eg, wedge biopsy of liver).
Cytology
Cytology involves the examination and interpretation of dispersed cells rather than
solid tissues, usually for the diagnosis of cancer and pre-cancerous lesions. These cells can
be obtained by a variety of methods according to the organ being investigated:
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- exfolifative cytology: cells shed from, or scraped or brushed off, an epithelial surface
(eg, bronchus, cervix)
- fluid cytology: cells withdrawn with the fluid in which they are suspended (eg,
peritoneal and pleural effusions, urine)
- washings: cells flushed out of an organ using an irrigating fluid (eg, bronchial
washings from the lung)
- fine-needle aspiration cytology: cells sucked out of a solid tissue (eg, breast lump)
using a thin needle attached to a syringe.
Blood
Blood is easy to sample by venepuncture; arterial blood is necessary only when gas
analyses (eg, O2, CO2) are to be performed. Many observations and measurements can be
made on blood smaples; for example:
- blood cells: the morphology and concentration in the blood are important in the
investigation and diagnosis of anaemias, leukaemias, infections, and immune status
- serum: commonly used (because it does not coagulate) for biochemical assays of
electrolytes, enzymes, proteins, etc.
Effusions of fluid into body cavities (eg, peritoneal, pleural) may be due to a variety
of causes. Measuring the protein concentration in the fluid may be helpful in distinguishing
between different mechanisms by which the fluid might have accumulated. Of greater value,
however, is cytological examination for neoplastic cells.
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Effusions and exudates (eg, pus and pathological discharges) may also be provoked
by infections. Microbiological examination of the material is vitally important in such cases
so that the casative organism can be identified and the most appropriate treatment prescribed.
Autopsies
Autopsy (necropsy and post-mortem examination are synonymous) means to 'see for
onself'. In other words, rather than relying on clinical signs and symptoms and the results of
diagnostic investigations during life, here is an opportunity for direct inspection and analysis
of the organs.
Autopsies are not restricted to the study of just those diseases that have proved fatal;
during the course of an autopsy, particularly in the elderly, it is not unusual to find evidence
of other diseases that have not contributed to death but which are nevertheless important to
note for epidemiological and other purposes.
From cadavers, we are able to obtain much information about the extent of a disease
and the way in which it has fatal consequences. Post-mortem autolysis, however, means that
there are limitations to how much detailed knowledge can be obtained; the proteolytic
enzymes naturally resident in tissues leak out of the lysosomes in which they are normally
sequestrated and slowly digest the cells. In some cases electron microscopy is helpful, though
this depends on the degree of autolysis. Post-mortem biochemistry is often useful, particularly
in toxicology or the detection of severe abnormalities of, for example, electrolytes and blood
lipids.
There has been a regrettable decline in the autopsy rate in most hospitals during the
latter half of the 20th century. Formerly, it was not unusual to find that the autopsy rate (as
a percentage of deaths) was 60% or higher; now, in many hospitals in the developed world,
it is 25% or lower. There are several reasons for this decline.
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Many clinicians directly responsible for patient care (eg, physicians and surgeons)
seem increasingly disinterested in the autopsy. They may feel that, having investigated the
patient during life, using all modern methods, there is nothing more to be learned from an
autopsy. They may feel absolutely confident about their diagnosis. However, several recent
studies in the UK and USA have shown that up to 30% of major clinical diagnoses are not
confirmed at autopsy. The autopsy makes, therefore, a major contribution to clinical audit by
verifying or refuting diagnoses made during life and by revealing hitherto unsuspected
disease.
For the medical undergraduates and postgraduates, the autopsy is an important medium
for the learning of pathology. It is an unrivalled opportunity to correlate clinical signs with
their underlying pathological explanation.
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