DEFINITIONDEFINITION::

-- Pathology is the scientific study of Pathology is the scientific study of disease. disease.

-- The ultimate goal of pathology is the The ultimate goal of pathology is the identification of the causes of disease, identification of the causes of disease, a fundamental objective that leads the a fundamental objective that leads the way to disease treatment and way to disease treatment and prevention.prevention.

Clinical PathologyClinical PathologyClinical medicine is based on a longitudinal Clinical medicine is based on a longitudinal approach to a patient’s illness - the patient’s history, approach to a patient’s illness - the patient’s history, the examination and investigation, the diagnosis and the examination and investigation, the diagnosis and the treatment. Clinical pathology is more concerned the treatment. Clinical pathology is more concerned with a cross-sectional analysis at the level of the with a cross-sectional analysis at the level of the disease itself, studied in depth - the cause and disease itself, studied in depth - the cause and mechanism of the disease, and the effects of the mechanism of the disease, and the effects of the disease upon the various organs and systems of the disease upon the various organs and systems of the body. These two perspectives are complementary body. These two perspectives are complementary and inseparable: clinical medicine cannot be and inseparable: clinical medicine cannot be practised without an understanding of pathology; practised without an understanding of pathology; pathology is meaningless if it is without clinical pathology is meaningless if it is without clinical implications.implications.

Experimental PathologyExperimental PathologyExperimental pathology is the Experimental pathology is the observation of the effects of observation of the effects of manipulations on experimental manipulations on experimental systems such as animal models of systems such as animal models of disease or cell cultures.disease or cell cultures.

Subdivisions of PathologySubdivisions of PathologyPathology is a vast subject with many Pathology is a vast subject with many ramifications (branches). In practice, ramifications (branches). In practice, however, it can be split into major however, it can be split into major subdivisions:subdivisions:

** Histopathology: the investigation and Histopathology: the investigation and diagnosis of disease from the diagnosis of disease from the examination of tissues.examination of tissues.

** Cytopathology: the investigation and Cytopathology: the investigation and diagnosis of disease from the diagnosis of disease from the examination of isolated cells.examination of isolated cells.

** Haematology: the study of disorders of the cellular Haematology: the study of disorders of the cellular and coagulable components of blood.and coagulable components of blood.

** Microbiology: the study of infectious diseases and Microbiology: the study of infectious diseases and the organisms responsible for them.the organisms responsible for them.

** Immunology: The study of the specific defense Immunology: The study of the specific defense mechanisms of the body.mechanisms of the body.

** Chemical pathology: the study and diagnosis of Chemical pathology: the study and diagnosis of disease from the chemical changes in tissues and disease from the chemical changes in tissues and fluids.fluids.

** Genetics: the study of abnormal chromosomes and Genetics: the study of abnormal chromosomes and genes.genes.

** Toxicology: the study of the effects of known or Toxicology: the study of the effects of known or suspected poisons.suspected poisons.

** Forensic pathology: the application of pathology to Forensic pathology: the application of pathology to legal purpose (e.g. investigation of death in legal purpose (e.g. investigation of death in suspicious circumstances).suspicious circumstances).

TECHNIQUES OF PATHOLOGYTECHNIQUES OF PATHOLOGYLight microscopyLight microscopy

Advances in the optical quality of lenses have Advances in the optical quality of lenses have resulted in a wealth of new information about the resulted in a wealth of new information about the structure of tissues and cells in health and disease structure of tissues and cells in health and disease that can be obtained from their examination by light that can be obtained from their examination by light microscopy.microscopy.If solid tissues are to be examined by light If solid tissues are to be examined by light microscopy, the sample must first be thinly microscopy, the sample must first be thinly sectioned to permit the transmission of light and to sectioned to permit the transmission of light and to minimize the superimposition of tissue components. minimize the superimposition of tissue components. These sections are routinely cut from tissue These sections are routinely cut from tissue hardened by permeation with and embedding in wax, hardened by permeation with and embedding in wax, or less often, transparent plastic. For some or less often, transparent plastic. For some purposes (e.g. histochemistry, very urgent purposes (e.g. histochemistry, very urgent diagnosis) sections have to be cut from tissue that diagnosis) sections have to be cut from tissue that has been hardened rapidly by freezing (frozen has been hardened rapidly by freezing (frozen section). The sections are stained to help section). The sections are stained to help distinguish between different components of the distinguish between different components of the tissue (e.g. nuclei, cytoplasm, collagen).tissue (e.g. nuclei, cytoplasm, collagen).

Immunohistochemistry and immunofluorescenceImmunohistochemistry and immunofluorescence

Immunohistochemistry and immunofluorescence Immunohistochemistry and immunofluorescence employ antibodies (immunoglobulins with antigen employ antibodies (immunoglobulins with antigen specificity) to visualize substances in tissue specificity) to visualize substances in tissue sections or cell preparations; these techniques use sections or cell preparations; these techniques use antibodies linked chemically to enzymes or antibodies linked chemically to enzymes or fluorescence dyes respectively. fluorescence dyes respectively. Immunofluorescence requires a microscope Immunofluorescence requires a microscope specially modified for ultraviolet illumination and specially modified for ultraviolet illumination and the preparations are often not permanent (they the preparations are often not permanent (they fade). For these reasons, immunohistochemistry fade). For these reasons, immunohistochemistry has become more popular; in this technique, the has become more popular; in this technique, the end product is a deposit of opaque or colored end product is a deposit of opaque or colored material that can be seen with a conventional light material that can be seen with a conventional light microscope and does not deteriorate.microscope and does not deteriorate.

Electron MicroscopyElectron MicroscopyElectron microscopy has extended the Electron microscopy has extended the range of pathology to the study of range of pathology to the study of disorders at the organelles level, and to disorders at the organelles level, and to the demonstration of viruses in tissue the demonstration of viruses in tissue samples from some diseases.samples from some diseases.

Biochemical TechniquesBiochemical TechniquesBiochemical techniques applied to the Biochemical techniques applied to the body’s tissues and fluids in health and body’s tissues and fluids in health and disease are now one of the dominant disease are now one of the dominant influences on our growing knowledge of influences on our growing knowledge of pathological processes. The clinical role of pathological processes. The clinical role of biochemistry is exemplified by the biochemistry is exemplified by the importance of monitoring fluid and importance of monitoring fluid and electrolyte homeostasis in many disorders. electrolyte homeostasis in many disorders. Serum enzyme assays are used to assess Serum enzyme assays are used to assess the integrity and vitality of various tissues; the integrity and vitality of various tissues; for example, raised levels of cardiac for example, raised levels of cardiac enzymes in the blood indicate damage to enzymes in the blood indicate damage to cardiac myocytes.cardiac myocytes.

Haematological TechniquesHaematological TechniquesHaematological techniques are used in Haematological techniques are used in the diagnosis and study of blood the diagnosis and study of blood disorders. These techniques range disorders. These techniques range from relatively simple cell counting, from relatively simple cell counting, which can be performed electronically, which can be performed electronically, to assays of blood coagulation factors.to assays of blood coagulation factors.

Cell CulturesCell CulturesCell cultures are widely used in Cell cultures are widely used in research and diagnosis. They are an research and diagnosis. They are an attractive medium for research because attractive medium for research because of the ease with which the cellular of the ease with which the cellular environment can be modified and the environment can be modified and the responses to it monitored (observed). responses to it monitored (observed). Diagnostically, cell cultures are used to Diagnostically, cell cultures are used to prepare chromosome spreads for prepare chromosome spreads for cytogenetic analysis.cytogenetic analysis.

Medical MicrobiologyMedical MicrobiologyMedical microbiology is the study of Medical microbiology is the study of diseases caused by organisms such as diseases caused by organisms such as bacteria, fungi, viruses and parasites. bacteria, fungi, viruses and parasites. Techniques used include direct microscopy Techniques used include direct microscopy of appropriately stained material (e.g. pus), of appropriately stained material (e.g. pus), culture to isolate and grow the organism and culture to isolate and grow the organism and methods to identify correctly the cause of the methods to identify correctly the cause of the infection. In the case of bacterial infections, infection. In the case of bacterial infections, the most appropriate antibiotic can be the most appropriate antibiotic can be selected by determining the sensitivity of the selected by determining the sensitivity of the organism to a variety of agents.organism to a variety of agents.

Molecular PathologyMolecular PathologyMany advances are now coming from Many advances are now coming from the relatively new science of molecular the relatively new science of molecular pathology, defects in the chemical pathology, defects in the chemical structure of molecules arising from structure of molecules arising from errors in the genome, the sequence of errors in the genome, the sequence of bases that directs amino acid bases that directs amino acid synthesis.synthesis.

GENERAL AND SYSTEMATIC PATHOLOGYGENERAL AND SYSTEMATIC PATHOLOGY

Pathology is best taught and learnt in two Pathology is best taught and learnt in two stages:stages:

** General pathology: the mechanisms and General pathology: the mechanisms and characteristics of the principal types of characteristics of the principal types of disease process (e.g. congenital versus disease process (e.g. congenital versus acquired diseases, inflammation, tumours, acquired diseases, inflammation, tumours, degeneration).degeneration).

** Systematic pathology: the descriptions of Systematic pathology: the descriptions of specific diseases as they affect individual specific diseases as they affect individual organs or organ systems (e.g. appendicitis, organs or organ systems (e.g. appendicitis, lung cancer, atheroma).lung cancer, atheroma).

LEARNING PATHOLOGYLEARNING PATHOLOGY There are two apparent difficulties that face the new There are two apparent difficulties that face the new

student of pathology: language and process. student of pathology: language and process. Pathology, like most branches of science and Pathology, like most branches of science and medicine, has its own vocabulary of special terms: medicine, has its own vocabulary of special terms: these need to be learnt and understood not just these need to be learnt and understood not just because they are the language of pathology but because they are the language of pathology but because they are also a major part of the language because they are also a major part of the language of clinical medicine. The student must not confuse of clinical medicine. The student must not confuse the learning of the language with the learning of the the learning of the language with the learning of the mechanisms of disease and their effects on mechanisms of disease and their effects on individual organs and patients. For example, the individual organs and patients. For example, the term “hyperplasia” means an increase in the size of term “hyperplasia” means an increase in the size of an organ due to the proliferation of its constituent an organ due to the proliferation of its constituent cells; this definition must be learnt before the cells; this definition must be learnt before the student attempts to learn about the process of student attempts to learn about the process of hyperplasia.hyperplasia.

A logical and orderly way of thinking about A logical and orderly way of thinking about diseases and their characteristics must be diseases and their characteristics must be cultivated; for each entity the student should cultivated; for each entity the student should be able to run through the list of chief be able to run through the list of chief characteristics that apply to any disease:characteristics that apply to any disease:

** Incidence.Incidence.

** Aetiology.Aetiology.

** Pathogenesis.Pathogenesis.

** Pathological and clinical features.Pathological and clinical features.

** Complication and sequelae.Complication and sequelae.

** Prognosis.Prognosis.

MAKING DIAGNOSESMAKING DIAGNOSESDiagnosis is the act of naming a disease in an Diagnosis is the act of naming a disease in an individual patient. The diagnosis is important individual patient. The diagnosis is important because it enables the patient to benefit from because it enables the patient to benefit from treatment that is known, or is at least likely, to be treatment that is known, or is at least likely, to be effective from observing its effects on other patients effective from observing its effects on other patients with the same disease.with the same disease.The process of making diagnosis involves:The process of making diagnosis involves:

** Taking a clinical history to document symptoms.Taking a clinical history to document symptoms.** Examining the patient for clinical signs.Examining the patient for clinical signs.** If necessary, performing investigations guided by If necessary, performing investigations guided by

the provisional diagnosis based on signs and the provisional diagnosis based on signs and symptoms.symptoms.

Although experienced clinicians can diagnose many Although experienced clinicians can diagnose many patient’s diseases quite rapidly (and possibly patient’s diseases quite rapidly (and possibly reliably), the student will find that it is helpful to adopt reliably), the student will find that it is helpful to adopt a formal strategy based on a series of logical steps a formal strategy based on a series of logical steps leading to the graduate exclusion of various leading to the graduate exclusion of various possibilities and the emergence of a single diagnosis. possibilities and the emergence of a single diagnosis. For example:For example:

** First decide which organ or body system is likely to First decide which organ or body system is likely to be affected by the disease.be affected by the disease.

** From the signs and symptoms, decide which general From the signs and symptoms, decide which general category of disease (inflammation, tumours, etc) is category of disease (inflammation, tumours, etc) is likely to be present.likely to be present.

** Then, using other factors (age, gender (sex), previous Then, using other factors (age, gender (sex), previous medical history, etc). compute a diagnosis or a small medical history, etc). compute a diagnosis or a small number of possibilities for investigation.number of possibilities for investigation.

** Investigations should be performed only if the Investigations should be performed only if the outcome of each one can be expected to resolve the outcome of each one can be expected to resolve the diagnosis, or influence management if the diagnosis diagnosis, or influence management if the diagnosis is already known.is already known.

Diagnostic PathologyDiagnostic PathologyIn living patients, we investigate and In living patients, we investigate and diagnose their illness by applying diagnose their illness by applying pathological methods to the pathological methods to the examination of tissue biopsies and examination of tissue biopsies and body fluids.body fluids.

Biopsies and organ resectionsBiopsies and organ resectionsBiopsies are samples of tissue removed from Biopsies are samples of tissue removed from a patient for diagnostic purposes. Resection a patient for diagnostic purposes. Resection specimens (e.g. gastrectomies, specimens (e.g. gastrectomies, thyroidectomies) are the whole or part of an thyroidectomies) are the whole or part of an organ removed for a previously diagnosed organ removed for a previously diagnosed condition: In addition to their diagnostic condition: In addition to their diagnostic utility, much is being learned about the utility, much is being learned about the pathology of many diseases from the study pathology of many diseases from the study of these tissue samples.of these tissue samples.

Biopsies can be obtained by a variety of Biopsies can be obtained by a variety of methods:methods:

** Needle biopsy: from solid tissues using Needle biopsy: from solid tissues using a thick-bored cutting needle.a thick-bored cutting needle.

** Endoscopic biopsy: visually-guided Endoscopic biopsy: visually-guided biopsy of an internal body surface (e.g. biopsy of an internal body surface (e.g. alimentary or respiratory tracts.alimentary or respiratory tracts.

** Incisional biopsy: tissue removed by Incisional biopsy: tissue removed by surgical incision (e.g. wedge biopsy of surgical incision (e.g. wedge biopsy of liver).liver).

CytologyCytologyCytology involves the examination and interpretation of Cytology involves the examination and interpretation of dispersed cells rather than solid tissues, usually for the dispersed cells rather than solid tissues, usually for the diagnosis of cancer and pre-cancerous lesions. These diagnosis of cancer and pre-cancerous lesions. These cells can be obtained by a variety of methods according cells can be obtained by a variety of methods according to the organ being investigated:to the organ being investigated:

** Exfoliative cytology: cells shed from, or scraped or Exfoliative cytology: cells shed from, or scraped or brushed off, an epithelial surface (e.g. bronchus, cervix).brushed off, an epithelial surface (e.g. bronchus, cervix).

** Fluid cytology: cells withdrawn with the fluid in which Fluid cytology: cells withdrawn with the fluid in which they are suspended (e.g. peritoneal and pleural effusion, they are suspended (e.g. peritoneal and pleural effusion, urine).urine).

** Washing: cells flushed out of an organ using an irrigating Washing: cells flushed out of an organ using an irrigating fluid (e.g. bronchial washings from the lung).fluid (e.g. bronchial washings from the lung).

** Fine needle aspiration cytology: cells sucked out of a Fine needle aspiration cytology: cells sucked out of a solid tissue (e.g. breast lump) using a thin needle solid tissue (e.g. breast lump) using a thin needle attached to a syringe.attached to a syringe.

BloodBloodBlood is easy to sample by venepuncture; arterial Blood is easy to sample by venepuncture; arterial blood is necessary only when gas analyses (e.g. O2, blood is necessary only when gas analyses (e.g. O2, CO2) are to be performed. Many observations and CO2) are to be performed. Many observations and measurements can be made on blood samples; for measurements can be made on blood samples; for example:example:

** Blood cells: the morphology and concentration in Blood cells: the morphology and concentration in the blood are important in the investigation and the blood are important in the investigation and diagnosis of anaemias, leukaemias, infections and diagnosis of anaemias, leukaemias, infections and immune status.immune status.

** Plasma: for the investigation of abnormalities of Plasma: for the investigation of abnormalities of blood coagulation.blood coagulation.

** Serum: commonly used (because it does not Serum: commonly used (because it does not coagulate) for biochemical assays of electrolysis, coagulate) for biochemical assays of electrolysis, enzymes, proteins, etc.enzymes, proteins, etc.

Excretion and secretionsExcretion and secretionsUrine and faeces are commonly investigated by Urine and faeces are commonly investigated by microbiological methods in cases of suspected microbiological methods in cases of suspected infection of the urinary tract and gastrointestinal infection of the urinary tract and gastrointestinal tract respectively. In some non-infectious tract respectively. In some non-infectious conditions, biochemical analyses (of urine and conditions, biochemical analyses (of urine and faeces) are helpful.faeces) are helpful.Sputum is an important source of diagnostic Sputum is an important source of diagnostic material in respiratory tract disease. Malignant cells material in respiratory tract disease. Malignant cells may be shed from the surface of a bronchial tumour may be shed from the surface of a bronchial tumour and expectorated in the sputum where they can be and expectorated in the sputum where they can be found by cytological examination. In lower found by cytological examination. In lower respiratory tract infections (bronchitis and respiratory tract infections (bronchitis and pneumonia), the causative organisms can often be pneumonia), the causative organisms can often be found in the sputum by microbiological methods.found in the sputum by microbiological methods.

Effusions and ExudatesEffusions and ExudatesEffusions of fluid into body cavities (e.g., peritoneal, Effusions of fluid into body cavities (e.g., peritoneal, pleural) may be due to a variety of causes. pleural) may be due to a variety of causes. Measuring the Measuring the proteinprotein concentration in the fluid may concentration in the fluid may be helpful in distinguishing between different be helpful in distinguishing between different mechanisms by which the fluid might have mechanisms by which the fluid might have accumulated. Of greater value, however, is accumulated. Of greater value, however, is cytological examination of the body fluids for cytological examination of the body fluids for neoplastic cells.neoplastic cells.Effusions and exudates (e.g., pus and pathological Effusions and exudates (e.g., pus and pathological discharges) may also be provoked by infections. discharges) may also be provoked by infections. Microbiological examination of the material is vitally Microbiological examination of the material is vitally important in such cases so that the causative important in such cases so that the causative organisms can be identified and the most organisms can be identified and the most appropriate treatment prescribed.appropriate treatment prescribed.

AUTOPSIESAUTOPSIESAutopsy (necropsy and post-mortem Autopsy (necropsy and post-mortem examination are synonymous) means examination are synonymous) means to “see for oneself”. In other words, to “see for oneself”. In other words, rather than relying on clinical signs and rather than relying on clinical signs and symptoms and the results of diagnostic symptoms and the results of diagnostic investigations during life, here is an investigations during life, here is an opportunity for direct inspection and opportunity for direct inspection and analysis of the organs.analysis of the organs.

Autopsies are useful for:Autopsies are useful for:** Determining the cause of death.Determining the cause of death.** Audit (assess or check) the accuracy of Audit (assess or check) the accuracy of

clinical diagnosis.clinical diagnosis.** Education of undergraduates and Education of undergraduates and

postgraduates.postgraduates.** Research into the causes and Research into the causes and

mechanisms of disease.mechanisms of disease.** Gathering accurate statistics about Gathering accurate statistics about

disease incidence.disease incidence.