What is pathology?

Morbid anatomy

Some of the greatest advances in our understanding of disease emerged from internal examination of the body after death. Autopsies (necropsies or postmortem examinations) have been performed since about 300 bc and have 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 . A notable landmark was the publication in 1761 of De Sedibus et Causis Morborum per Anatomem Indagatis by Giovanni Morgagni (1682–1771). During the 18th and 19th centuries in Europe, medical science was further advanced by Matthew Baillie (1761–1823), Carl von Rokitansky (1804–1878) and Ludwig Aschoff (1866–1942). They meticulously performed and documented many thousands of autopsies and, crucially, correlated their findings with the clinical signs and symptoms of the patients and with the natural history of numerous diseases.

Microscopic and cellular pathology

Pathology, and indeed medicine as a whole, was revolutionised by the application of microscopy to the study of diseased tissues from about 1800. Previously, it was commonly believed that tissue alterations in disease resulted from a process of spontaneous generation ; that is, by metamorphosis independent of any external cause or other influence. Today, this notion seems ridiculous, but 200 years ago nothing was known of bacteria, viruses, ionising radiation, carcinogenic chemicals, and so on. Louis Pasteur's (1822–1895) demonstration that microorganisms in the environment could contaminate and impair the quality of wine was a major advance in our perception of the environment and our knowledge that pathogens within it, invisible to the naked eye, cause disease.

Rudolf Virchow (1821–1902), a German physician and pathologist and an ardent advocate of the microscope, recognised that cells were the smallest viable constituent units of the body. Building on the work of Theodor Schwann (1810–1882) he formulated a new and lasting set of ideas about disease — cellular pathology . The light microscope enabled diseased tissues to be viewed at a cellular level. His observations, extended further by electron microscopy, have had a profound and enduring influence. But Virchow's cell pathology theory is neither complete nor immutable; advances in biochemistry have revolutionised our understanding of many diseases at a molecular level.

Molecular pathology

The impact of molecular pathology is exemplified by advances in our knowledge of the biochemical basis of congenital disorders and cancer. Techniques with relatively simple principles (less easy in practice) reveal the change of a single nucleotide in genomic DNA resulting in the synthesis of the defective gene product that is the fundamental lesion in a particular disease ( Ch. 3 ).

Cellular and molecular alterations in disease

Modern scientific methods have resulted in a clearer understanding of the ways in which diseases result from disturbed normal cellular and molecular mechanisms ( Table 1.2 ).

Clinical pathology

Clinical medicine involves a longitudinal approach to a patient's illness — the patient's history, the examination and investigation, the diagnosis, the treatment and follow-up. Clinical pathology is more concerned with a cross-sectional analysis at the level of the disease itself, studied in depth — the cause and mechanisms of the disease, and the effects of the disease upon the various organs and systems of the body. These two perspectives are complementary and inseparable: clinical medicine cannot be practised effectively without understanding pathology; pathology is meaningless if it lacks clinical significance.

Approximately 70% of clinical diagnoses rely on pathology investigations. In the USA, c . 90% of the objective data in electronic patient records are derived from pathology laboratories.

Pathology in clinical practice includes:

• histopathology : the investigation and diagnosis of disease from the examination of tissues

• cytopathology : the investigation and diagnosis of disease from the examination of isolated cells

• haematology : the study of disorders of the cellular and coagulable components of blood

• microbiology : the study of infectious diseases and the organisms responsible for them

• immunology : the study of the specific defence mechanisms of the body

• chemical pathology : the study and diagnosis of disease from the chemical changes in tissues and fluids

• genetics : the study of abnormal chromosomes and genes

• toxicology : the study of the effects of known or suspected poisons

• forensic pathology : the use of pathology for legal purposes (e.g. investigation of death in suspicious circumstances).

These subdivisions are more important professionally (because each requires its own team of trained specialists) than educationally at the undergraduate level. Pathology must be taught and learnt in an integrated manner, for the body and diseases make no distinction between these professional subdivisions. This book, therefore adopts a multidisciplinary approach to pathology. In the systematic section (Part 3), the normal structure and function of each organ is summarised, the pathological basis for clinical signs and symptoms is described, and the clinical implications of each disease are emphasised.

Gross pathology

Before microscopy was applied to medical problems ( c . 1800), observations were limited to those made with the naked eye, and thus was accumulated much of our knowledge of the morbid anatomy of disease. Gross or macroscopic pathology is the modern nomenclature for this approach to the study of disease and, especially in the autopsy, is still important. The gross pathology of some diseases is so characteristic that, when interpreted by an experienced pathologist, a fairly confident diagnosis can be given before further investigation by, for example, light microscopy.

Light microscopy

Advances in optics have yielded much new information about the structure of tissues and cells in health and disease. Before solid tissues are 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 usually cut from tissue hardened by embedding in wax or, less often, transparent plastic. For urgent or intraoperative diagnosis, sections are cut from tissue hardened by rapid freezing. Tissue sections are stained to help distinguish between different components (e.g. nuclei, cytoplasm, collagen).

The microscope can also be used to examine cells from cysts, body cavities, sucked from solid lesions or scraped from body surfaces. This is cytology and it is used widely in, for example, cancer screening.

Histochemistry

Histochemistry is the study of the chemistry of tissues, usually by microscopy of tissue sections after they have been treated with specific reagents so that the biochemical features of individual cells can be visualised.