Pathological Anatomy - 1 Lecture # 1 Milyushina Ya.A.

Lecture # 1 Pathologic anatomy: its content & tasks. Service of pathologic anatomy, its role & place in system of Public Health Service. PLAN: 1. 2. 3. 4. 5. Definition of pathologic anatomy. Periods of development of pathologic anatomy. Brief history of pathological anatomy. Content of general and systemic pathological anatomy. Definition of disease. Characteristic of pathological process: 4 basic moments. Pathomorphosis. 6. Methods of pathological anatomy. 7. Service of pathologic anatomy, its role & place in system of Public Health Service. Pathology is literally the study (logos) of suffering (pathos). There are a lot of names of this discipline in different countries: pathologic anatomy, pathomorphology, morbid anatomy, anatomical pathology, histopathology, surgical pathology etc. We use term pathological anatomy. More specifically, it is a bridging discipline involving both basic science and clinical practice and is devoted to the study of the structural and functional changes in cells, tissues, and organs that underlie disease. By the use of molecular, microbiologic, immunologic, and morphologic techniques, pathology attempts to explain the whys and wherefores of the signs and symptoms manifested by patients while providing a sound foundation for rational clinical care and therapy. There are fore periods in development of pathologic anatomy: 1. Anatomical period (from ancient times till XIX c.) 2. Microscopical period (from 1st third of XIX c. till 50-es years of XX c.) 3. Ultramicroscopical period (after XIX c. till 50-es years of XX c.) 4. Modern period (pathology of alive man) Early systematic human dissections were carried out by the Ancient Greek physicians Herophilus of Chalcedon and Erasistratus of Chios in the early part of the third century BC. The Greek physician Hippocrates, the founder of scientific medicine, was the first to deal with the anatomy and the pathology of human spine. Galen developed an interest in anatomy from his studies of Herophilus and Erasistratus. The concept of studying disease through the methodical dissection and examination of diseased bodies, organs, and tissues may seem obvious today, but there are few if any recorded examples of true autopsies performed prior to the second millennium. Though the pathology of contagion was understood by Muslim physicians since the time of Avicenna (9801037) who described it in The Canon

Pathological Anatomy - 1 Lecture # 1 Milyushina Ya.A.

of Medicine (c. 1020), the first physician known to have made postmortem dissections was the Arabian physician Avenzoar (10911161) who proved that the skin disease scabies was caused by a parasite, followed by Ibn al-Nafis (b. 1213) who used dissection to discover pulmonary circulation in 1242. In the 15th century, anatomic dissection was repeatedly used by the Italian physician Antonio Benivieni (1443-1502) to determine cause of death. Antonio Benivieni is also credited with having introduced necropsy to the medical field. Perhaps the most famous early gross pathologist was Giovanni Morgagni (1682-1771). His magnum opus, De Sedibus et Causis Morborum per Anatomem Indagatis, published in 1761, describes the findings of over 600 partial and complete autopsies, organised anatomically and methodically correlated with the symptoms exhibited by the patients prior to their demise. Although the study of normal anatomy was already well advanced at this date, De Sedibus was one of the first treatises specifically devoted to the correlation of diseased anatomy with clinical illness. By the late 1800s, an exhaustive body of literature had been produced on the gross anatomical findings characteristic of known diseases. The extent of gross pathology research in this period can be epitomized by the work of Carl Rokitansky (1804-1878), who is said to have performed 20,000 autopsies, and supervised an additional 60,000, in his lifetime. Rudolf Virchow (1821-1902) is generally recognized to be the father of microscopic pathology. While the compound microscope had been invented approximately 150 years prior, Virchow was one of the first prominent physicians to emphasize the study of manifestations of disease which were visible only at the cellular level. A student of Virchow's, Julius Cohnheim (1839-1884) combined histology techniques with experimental manipulations to study inflammation, making him one of the earliest experimental pathologists. Cohnheim also pioneered the use of the frozen section procedure; a version of this technique is widely employed by modern pathologists to render diagnoses and provide other clinical information intraoperatively. Traditionally, the study of pathology is divided into general pathology and special or systemic pathology. The former is concerned with the basic reactions of cells and tissues to abnormal stimuli that underlie all diseases. The latter examines the specific responses of specialized organs and tissues to more or less well defined stimuli. Pathologic anatomy serves both to theory of medicine and to clinical practice. Theoretical meaning of pathologic anatomy is opening in studying of general rules of development of cell pathology, pathologic processes & diseases. General pathology is above all cell pathology & morphology of general pathological processes, & it is content of course of general pathological anatomy. Clinical meaning of pathologic anatomy is studying of structural bases of human diseases, specificity of certain disease, in creating of clinical anatomy. Studying of general and special pathologic anatomy is inseparably linked because general pathological processes in different combinations are substance of syndromes & human diseases. And studying of structural bases of syndromes & diseases is carried out in
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Pathological Anatomy - 1 Lecture # 1 Milyushina Ya.A.

interaction with studying of their clinical appearance. Disease is any deviation from or' interruption of the normal structure or function of any organ or system of the body that is manifested by a characteristic set of signs and symptoms. Structural & functional changes are always connected between each other. So the studying of pathologic anatomy is based of principle of unity& connection of structure & function. The four aspects of a disease process that form the core of pathology are its cause (etiology), the mechanisms of its development (pathogenesis), the structural alterations induced in the cells and organs of the body (morphologic changes), and the functional consequences of the morphologic changes (clinical significance). Etiology or Cause. In modern terms, there are the two major classes of etiologic factors: intrinsic or genetic and acquired (e.g., infectious, nutritional, chemical, physical). Knowledge or discovery of the primary cause remains the backbone on which a diagnosis can be made, a disease understood, or a treatment developed. The concept, however, of one etiologic agent to one disease developed from the study of infections or single-gene disordersis no longer sufficient. Genetic factors are clearly involved in some of the common environmentally induced maladies, such as atherosclerosis and cancer, and the environment may also have profound influences on certain genetic diseases. There are two groups of etiology: I. Genetical due to abnormalities of chromosomes, called mutations or defect in genes II. Acquired: which may be caused by: a) Physical agents. b) Chemical poisons. c) Nutritional deficiencies. d) Infections. e) Abnormal immunological reactions. f) Psychological factors. Pathogenesis. Pathogenesis refers to the sequence of events in the response of the cells or tissues to the etiologic agent, from the initial stimulus to the ultimate expression of the disease. The study of pathogenesis remains one of the main domains of pathology. Even when the initial infectious or molecular cause is known, it is many steps removed from the expression of the disease. For example, to understand cystic fibrosis is to know not only the defective gene and gene product but also the biochemical, immunologic, and morphologic events leading to the formation of cysts and fibrosis in the lung, pancreas, and other organs. Indeed, as we shall see throughout the book, the molecular revolution has already identified mutant genes underlying a great number of diseases and promises to map the entire human genome before too long. Nevertheless, the functions of the encoded proteins and how mutations induce disease are often still obscure. Thus, the study of pathogenesis has never been more exciting scientifically or more
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Pathological Anatomy - 1 Lecture # 1 Milyushina Ya.A.

relevant to the development of new therapies. Morphologic Changes. The morphologic changes refer to the structural alterations in cells or tissues that are either characteristic of the disease or diagnostic of the etiologic process. Functional Derangements and Clinical Significance. The nature of the morphologic changes and their distribution in different organs or tissues influence normal function and determine the clinical features (symptoms and signs), course, and prognosis of the disease. Task of pathologic anatomy is working out of studying about diagnosis. Pathologic anatomy takes attention to changeability of diseases (pathomorphosis) & to diseases, which appears because of doctors activity (iatrogeny). Pathomorphosis is wide notion, which reflects: 1. changes in structure of morbidity & lethality, connected with changes in human life conditions; 2. stable changes of clinico-morphological appearances of certain disease, nosology (nosomorphosis), arising with the use of medicine (theraupeutical pathomorphosis). Studying of structural bases of diseases is carried out on different levels: level of organism, systemic, on level of organ, tissue, cellular, subcellular, molecular. Studying of diseases on level of organism allows to consider it in interrelations of all organs & systems of organism. Systemic level is level of studying of certain system of organs or tissues united by common functions, for example system of connective tissue, digestive system etc.). Level of organs allows to reveal changes of organs & tissues. In one case it possible to see these changes macroscopically, in other case it need microscopical investigation. Tissue and cellular levels are levels of studying of changed tissues, cells and intercellular substance with light microscopical methods of investigations. Subcellular level allows observing the changes of ultrastructure of cells & intercellular substance with electron microscope. Molecular level of studying is possible with the use of complex of electron microscopy, cytochemistry, radioautography, immunohistochemistry. Methods of pathological anatomy: Gross examination - the examination of diseased tissues with the naked eye. This is important especially for large tissue fragments, because the disease can often be visually identified. It is also at this step that the pathologist selects areas that will be processed for histopathology. The eye can sometimes be aided with a magnifying glass or a stereo microscope, especially when examining
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Pathological Anatomy - 1 Lecture # 1 Milyushina Ya.A.

parasitic organisms. Histopathology - the microscopic examination of stained tissue sections using histological techniques. The standard stains are haematoxylin and eosin, but many others exist. The use of haematoxylin and eosin-stained slides to provide specific diagnoses based on morphology is considered to be the core skill of anatomic pathology. The science of staining tissues sections is called histochemistry. Immunohistochemistry - the use of antibodies to detect the presence, abundance, and localization of specific proteins. This technique is critical to distinguishing between disorders with similar morphology, as well as characterizing the molecular properties of certain cancers. In situ hybridization - Specific DNA and RNA molecules can be identified on sections using this technique. When the probe is labeled with fluorescent dye, the technique is called FISH. Cytopathology - the examination of loose cells spread and stained on glass slides using cytology techniques. Electron microscopy - the examination of tissue with an electron microscope, which allows much greater magnification, enabling the visualization of organelles within the cells. Its use has been largely supplanted by immunohistochemistry, but it is still in common use for certain tasks, including the diagnosis of kidney disease and the identification of immotile cilia syndrome among many others. Tissue cytogenetics - the visualization of chromosomes to identify genetics defects such as chromosomal translocation. Flow immunophenotyping - the determination of the immunophenotype of cells using flow cytometry techniques. It is very useful to diagnose the different types of leukemia and lymphoma.

Goals & tasks of service of pathology anatomy Service of pathology anatomy is the system of measures, directed to improvement of medical and diagnostic work in subdivisions of medical service. Main tasks: 1. Conducting of clinico-anatomical analysis of results of dissection of a corpse conjointly with charging doctors. 2. Maintenance of authentic data of official statistics of causes of the death. 3. Taking part in antemorten diagnostic of diseases, especially in the area of oncology, by researching of biopsy samples, and by researching of ablated organs and tissues. 4. Revealing of acute contagious diseases in sectional, operational and biopsy materials.

Pathological Anatomy - 1 Lecture # 1 Milyushina Ya.A.

5. 6. 7. 8.

Rise of physicians qualification by conjointly discussion of results of dissections and pathologic investigations, and by consultative assistance in the questions of pathology. Providing of clinico-anatomical conferences and participations in medical control commissions. Performing of the supervision of medico-diagnostic work with the aim of decrease of mistakes in diagnostic and treatment (by comparison of clinic and pathological diagnoses). Researches of actual problems of human pathology.

Organization of the work of the dissecting department Department of pathology (dissecting department) is organized in the structure of multiprofile hospitals depending on number of autopsies, investigations of biopsy samples, investigations of operative materials by staff norms. Main activity of prosectorium is directed to perfection of medical and diagnostic assistance to population by improvement of antemorten diagnostic of diseases, more precise definition of causes of death, supplying of authentic data of official statistics of causes of the death, rising of physicians qualification and performing of analysis of mistake in diagnostic and treatment. Furthermore Pathologic Bureau is a base for training for pathologists. For decision of above mentioned tasks the stuff of Pathology department performs macro- and microscopic investigations, if there is necessity it supplies taking of cadaver materials for bacteriologic, virological and chemical investigations, and performs investigations of operational and bioptic material. So, all objects for pathologic investigation may be divided into 3 groups: 1. Cadaveric material 2. Materials, which were taken from alive patients (organs, tissues, biological fluids etc.) 3. Experimental material Autopsy plays unique role in the disclosing of structural substance of diseases and dynamics of their development. An autopsy, also known as a post-mortem examination, necropsy (particularly as to animals), autopsia cadaverum, or obduction, is a medical procedure that consists of a thorough examination of a corpse to determine the cause and manner of death and to evaluate any disease or injury that may be present. The prefix 'auto-' means 'self', and so autopsy means 'to see for oneself'; it is used more broadly of personal examination of an object, as well as its specific usage for the post-mortem examination of a human corpse. General anatomical pathologists are trained in performing autopsies, which are used to determine the disease factors contributing to a person's death. Autopsies are important in the ongoing medical education of clinicians, and in
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Pathological Anatomy - 1 Lecture # 1 Milyushina Ya.A.

efforts to improve and verify the quality of medical care. Autopsy is permitted to perform in any time after biological death, but not later than 10.00 of next morning after death. The case history with direction of chief medical officer for autopsy must be present for pathologist before autopsy. The case history with filled pathologoanatomical diagnosis and epicrisis must be passed in medical archives of hospital not later than 5 days after autopsy. The autopsy maybe canceled by chief medical officer in exclusive cases (if there is application of relatives) by agreement with chief of Pathology department. The cancel of autopsy is forbid in next cases: 1. Death in hospital during 1st day. Suspicion on violent death. 2. Cases, which require forensic medical examination 3. Cases of infectional diseases and suspicion on HIV infection 4. All cases of unclear diagnosis 5. Cases of maternal death or death from gynecological diseases. Maternal death is death due to pregnancy irrespective of the period of pregnancy or after 42 days after delivery from the cause concerned with it, but not from any accidental cause 6. Cases of death of newborn or death in perinatal period 7. Cases of death in hospital after diagnostic procedures or after treatment Diagnosis, which pathologist forms just after autopsy is presumptive (preliminary). Final diagnosis is formed after histological examination of internal organs.