The development of pathological physiology as an independent science dates back to the second half of the 19th century, when significant advances were made in the field of biology, chemistry and physiology, which made it possible to begin a systematic study of the mechanisms of the occurrence of pathological processes and diseases. The emergence of pathological physiology as an independent discipline was greatly facilitated by the use of physiological experimental methods for the study of pathological processes.
The work of I. P. Pavlov (1852-1936) and his school had a particularly great influence on the development of pathophysiology. Many questions of the pathophysiology of blood circulation, digestion and especially higher nervous activity were developed by I. P. Pavlov and his students (A. D. Speransky, K. M. Bykov, L. A. Orbeli, etc.). I. P. Pavlov developed in pathophysiology the principles of integrity, nervism and verification in practice of the results obtained. The influence of the French physiologist Claude Bernard was also great, whose famous experiment - a “sugar injection” into the bottom of the fourth ventricle of the brain was the first experimental model of a human disease - diabetes mellitus.
In Russia, the development of pathological physiology (experimental pathology) is associated with the name of the great Russian physiologist. I. M. Sechenov and especially his student V. V. Pashutin, the founder of the first (independent department of general and experimental pathology at Kazan University (1814), as well as at the Military medical academy in St. Petersburg (1879). However, long before the organization of independent departments of pathological physiology, the main elements of the study of diseases (general pathology) were taught by clinicians or physiologists in the corresponding departments. During this period, pathology as a science containing a number of theoretical information about diseases was an introductory part to clinical disciplines, which is why it most often belonged to a single department of pathology, therapy and clinic. The first teachers of the elements of general pathology in hospital and medical schools in the 18th century were such outstanding clinicians as A. M. Shumlyansky (1748-1795), who occupied the department of therapy, obstetrics and pathological anatomy at the Moscow Hospital School, M. M. Terekhovsky (1740-1796), teacher of pharmacology, pathology and practical medicine at the Kronstadt Naval Hospital. At Moscow University, general pathology was taught by S. G. Zabelin (1735-1802), M. I. Barsuk-Moiseev (1768-1811). It is noteworthy that M.I. Barsuk-Moiseev was the first doctor of medicine at Moscow University; in 1794 he defended his dissertation on the topic “On Breathing.”
In the first half of the 19th century, a particularly large contribution to the teaching of general pathology was made by I. E. Dyadkovsky (1784-1841) and his student K. V. Lebedev (1802-1884), who taught a course in general pathology at Moscow University. K.V. Lebedev wrote a textbook on “General Anthropology” (1835), which was the first guide to general pathology in Russian. K.V. Lebedev, like his teacher I.E. Dyadkovsky, took a materialistic position in the analysis of the causes and essence of the disease. He emphasized fundamental difference human diseases (anthropology) from diseases of other living beings (zoopathology). But already during this period, Russian scientists clearly understood the importance of experimental research methods for studying the mechanisms of disease development. Thus, Professor of Moscow University A. M. Filomafitsky (1807-1849), head of the department of physiology and general pathology, for the first time in Russia carried out a number of purely pathophysiological experiments - removal of kidneys from animals, ligation of ureters, etc. He extensively developed the issues of blood transfusion, together with N.I. Pirogov, he studied the effect of narcotic drugs (chloroform, ether) on the animal body.
General pathology emerged as an independent discipline in 1863, but it was most often taught by pathologists. Thus, in Moscow, since 1863, a course in general pathology was taught by the famous pathologist A. I. Polunin (1820-1888). As a morphologist, he promoted experimental methods in pathology. In Kharkov the department of general pathology was headed by I. N. Obolensky, in Kyiv by N. A. Khrzhonshchevsky, in Kazan from 1867 to 1872 by M. F. Subbotin. Identification of general pathology in independent discipline had great value For further development this important branch of medicine as an experimental science. For Russian pathology the second half of the 19th century The century is characterized by a transition from the morphological direction to the positions of experimental pathology, i.e. pathological physiology.
The increasingly widespread use of experimental research methods in pathology and the accumulation of experimentally obtained factual material have led to the need to separate the teaching of general pathology from morphology (pathological anatomy) and the creation of departments of experimental pathology (pathological physiology). The first department of general and experimental pathology in Russia was organized at Kazan University in 1874 by V. V. Pashutin, who transformed general pathology from a speculative science into an experimental one. As a student of I.M. Sechenov and S.P. Botkin, he developed the ideas of nervism in pathophysiology. V.V. Pashutin wrote the first original guide to pathological physiology, which has not lost its significance to this day. V.V. Pashutin's scientific interests were focused on the main problem of pathology - metabolic disorders. His work in the field of complete and partial fasting is especially valuable. He developed an original method for studying gas exchange and was the first to create a calorimeter to directly determine heat loss by the body of animals and humans. V.V. Pashutin for the first time in Russia began to study the activity of glands internal secretion(sex glands). The name of V.V. Pashutin is also notable for the fact that he is the creator of the first scientific school of pathophysiologists in Russia. His students developed the direction started by V.V. Pashutin in the study of the pathophysiology of metabolism. A number of his students later headed departments of general pathology at Russian universities: A. M. Albidkiy (Military Medical Academy in St. Petersburg), A. V. Reprev (Tomsk, Kharkov), N. G. Ushinsky (Warsaw, Odessa), etc. .
Simultaneously with the St. Petersburg one, the Moscow scientific school of pathophysiologists was created, coming from A. I. Polunin and his student A. B. Fokht (1848-1930). A characteristic feature of this direction was close contact with the clinic. A. B. Fokht has carried out outstanding research on cardiac pathology, edema, dropsy, inflammation of the pericardial sac, functional and anatomical changes in the heart during coronary artery embolism, circulatory disorders and cardiac activity during embolism pulmonary artery. Major representatives The Moscow school of pathophysiologists also headed the departments of general pathology and pathological physiology at various universities: in Kyiv (V. Lindeman), Moscow (G. P. Sakharov, A. I. Talyantsev), Minsk (F. A. Andreev), etc.
A major role in the development of general pathology as an experimental science was played by V. V. Podvysotsky (1857-1913), who headed the department of general pathology in Kyiv from 1887. Such famous scientists as I. G. Savchenko, L. A. Tarasevich, D. K. Zabolotny, A. A. Bogomolets and others came from his school. V. V. Podvysotsky’s scientific interests were concentrated in the field of studying regeneration and the pathogenesis of neoplasms , immunity. He wrote the textbook “General and Experimental Pathology,” translated into all European and a number of Asian languages. At the end of the 19th and beginning of the 20th centuries, the textbook served as the main guide for the study of experimental pathology in Russia and abroad.
A special place in the history of pathophysiology is occupied by I. I. Mechnikov, whose work on inflammation, immunity, atrophy and self-poisoning of the body is classic. I. I. Mechnikov created a comparative pathological direction in the study of pathological processes. Phagocytic theory inflammation, the study of immunity and the infectious process are the basis of many studies carried out in these areas at the present time.
Pathological physiology as a scientific discipline received especially broad prospects for development after the Great October Revolution. socialist revolution. From the very beginning during the reform medical education pathological physiology began to be given great importance as a discipline that plays an exceptional role in shaping the worldview of a Soviet doctor. In 1924, on the initiative of A. A. Bogomolets and S. S. Khalatov, the name “Department of Pathological Physiology” was officially adopted on an all-Union scale for the former departments of general pathology. Departments and research laboratories of pathological physiology were headed by prominent experimental scientists. The work of these departments received a strictly experimental direction. A number of large original schools of Soviet pathophysiologists arose: N. N. Anichkova (Leningrad), A. A. Bogomolets (Saratov, Moscow, Kiev), V. V. Voronina (Odessa, Tbilisi), N. N. Sirotinina (Kazan, Kiev ), I. R. Petrova (Leningrad), etc.
N. N. Anichkov (1885-1964) from 1919 to 1938 headed the department of pathological physiology of the Military Medical Academy. In 1946 he was elected the first president of the Academy medical sciences. N. N. Anichkov with a large team of employees developed issues of diseases of cardio-vascular system, physiology and pathology of the reticuloendothelial system, pathogenesis of autoinfections, etc. The theory of infiltration origin of atherosclerosis is associated with the name of N. N. Anichkov. Such prominent pathophysiologists as I.R. Petrov, P.N. Veselkin, P.P. Goncharov and others came out of this school.
A large, fruitful school was created in Odessa and Tbilisi by the famous Russian scientist V.V. Voronin (1870-1960). His works were devoted to pathophysiology, microbiology and epidemiology, zoology, morphology and some problems of physics and mathematics. Basic scientific interests V.V. Voronin and his students were concentrated around the general pathology of inflammation, blood circulation, peripheral nervous system. In 1947-1948 V.V. Voronin published a two-volume textbook on pathological physiology, where the laws of mechanics, physics and mathematics were used to solve problems of the pathogenesis of diseases.
A. A. Bogomolets (1881-1946) had a great influence on the development of domestic pathophysiology. Bogomolets worked in Saratov, Moscow and Kiev and is the founder of the largest school of Soviet pathophysiologists. The central problem developed by the school of A. A. Bogomolets was the problem of reactivity A lot of work was devoted to studying the reactions connective tissue for various pathological processes, issues of blood transfusion, endocrine pathology, cytotoxic stimulation of functions. Under the editorship of A. A. Bogomolets, the first multi-volume manual on pathological physiology was created (1940-1946). From the school of A. A. Bogomolets such outstanding scientific pathophysiologists as N. N. Sirotinin, N. A. Fedorov, P. D. Gorizontov and others came out.
The most active continuer of the study of the problem of reactivity in pathology and physiology is currently N. N. Sirotinin and his school. The great merit of N. N. Sirotinin and his school is the development of questions about comparative pathology reactivity, allergies, immunity and infectious process. N. N. Sirotinin has been systematically studying issues since 1929 oxygen starvation and adaptation to hypoxia. Under the general editorship of N. N. Sirotinin in Lately a 4-volume manual on pathological physiology was created (1966).
I. R. Petrov (1893-1970) all his creative life dedicated to work at the Department of Pathophysiology of the Military Medical Academy. Together with his many students, he intensively and successfully developed the problems of oxygen starvation, pathogenesis traumatic shock, blood loss, blood transfusion, hypothermia and resuscitation, pathological regulation of blood circulation, etc.
A major role in the development of ideas about the importance of the nervous system in pathology was played by the research of A.D. Speransky (1888-1961), for example, his widely known work on nervous trophism, epilepsy, trace aftereffects in pathology, etc. Student of A.D. Speransky A. M. Chernukh fruitfully develops the problems of recovery and experimental therapy.
Pathological anatomy is an integral part of pathology - a science that studies the patterns of occurrence and development of diseases, individual pathological processes and conditions.
In the history of the development of pathological anatomy, four main periods are distinguished: anatomical (from antiquity to early XIX century), microscopic (from the first third of the 19th century to the 50s of the 20th century), ultramicroscopic (after the 50s of the 19th century); the modern, fourth period of development of pathological anatomy can be characterized as the period of pathological anatomy of a living person.
Possibility of studying pathological changes in organs human body appeared in the XV-XVII centuries thanks to the emergence and development of scientific anatomy. The most significant role in the creation of a method of anatomical research, description of the structure of all the most important organs and their relative positions was played in the middle of the 16th century by the works of A. Vesalius, G. Fallopius, R. Colombo and B. Eustachius.
Anatomical studies of the second half of the 16th - early 17th centuries not only strengthened the position of anatomy, but also contributed to the emergence of interest in anatomy among doctors. The philosopher F. Bacon and the anatomist W. Harvey had a significant influence on the development of anatomy during this period.
In 1676, T. Bonet made the first attempt, using significant material (3000 autopsies), to show the existence of a connection between the morphological changes discovered and the clinical manifestations of the disease.
In the 17th century, the richest anatomical museums appeared in Europe (Leiden), in which pathological and anatomical preparations were widely represented.
The most important event in the history of pathological anatomy, which determined its separation into an independent science, was the publication in 1761 of the main work of J.B. Morgani “On the location and causes of diseases identified by the anatomist.”
At the turn of the 18th and 19th centuries in France, J. Corvisart, R. La-ennec, G. Dupuytren, K. Lobstein, J. Buyot, J. Cruvelier widely introduced pathological anatomy into clinical practice; M.K.Bisha pointed out further path its development - the study of damage at the tissue level. M.K.Bish's student F.Brousse created a doctrine that rejected the existence of diseases that do not have a material substrate. J. Cruvelier released in 1829-1835. The world's first color atlas on pathological anatomy.
In the middle of the 19th century, the greatest influence on the development of this branch of medicine was exerted by the works of K. Rokitansky, in which he not only presented changes in organs at various stages of disease development, but also clarified the description of pathological changes in many diseases. In 1844, K. Rokitansky founded the Department of Pathological Anatomy at the University of Vienna and created the world's largest pathological anatomical museum. The name of K. Rokitansky is associated with the final separation of pathological anatomy into an independent scientific discipline and medical specialty.
The turning point The development of this discipline was the creation in 1855 by R. Virchow of the theory of cellular pathology.
In Russia, the first attempts to organize autopsy work date back to XVIII century. They are associated mainly with the activities of prominent health care organizers - I. Fisher and P. Z. Kondoidi. These attempts did not produce tangible results due to the low level of development of Russian medicine and the state of medical education, although already at that time separate autopsies were carried out for control, diagnostic and research purposes.
The emergence of pathological anatomy as a scientific discipline began only in the first quarter of the 19th century and coincided with the improvement of the teaching of normal anatomy at universities. One of the first anatomists to draw students' attention to pathological changes organs during the autopsy, was E.O. Mukhin.
For the first time, the question of the need to include pathological anatomy among the compulsory subjects of teaching at Faculty of Medicine Moscow University was appointed in 1805 by M.Ya. Mudrov in a letter to the university trustee M.N. Muravyov. At the suggestion of Yu.H. Loder, the teaching of pathological anatomy in the form of a course at the department of normal anatomy was reflected in the university charter of 1835. In accordance with this charter, the teaching of an independent course of pathological anatomy was started in 1837 by prof. L.S. Sevruk at the Department of Normal Anatomy. Professors G.I. Sokolsky and A.I. Over began to use the latest pathological and anatomical information in teaching therapeutic disciplines, and F.I. Inozemtsev and A.I. Pol - when giving lectures on surgery courses.
In 1841, in connection with the creation of a new medical faculty in Kyiv, N.I. Pirogov raised the question of the need to open a department for teaching pathology at the University of St. Vladimir. In accordance with the charter of this university (1842), the opening of the department of pathological anatomy and pathological physiology was provided for, which began to function in 1845: it was headed by N.I. Pirogov’s student N.I. Kozlov.
On December 7, 1845, the “Additional Decree on the Medical Faculty of the Imperial Moscow University” was adopted, which provided for the creation of the department of pathological anatomy and pathological physiology. In 1846, Yu. Dietrich, an adjunct of the faculty therapeutic clinic, headed by A.I. Over, was appointed professor of this department. After the death of J. Dietrich, four adjuncts from the therapeutic clinics of Moscow University took part in the competition to fill the vacant position - Samson von Gimmelstern, N.S. Toporov, A.I. Polunin and K.Ya. Mlodzievsky. In May 1849, A.I. Polunin, an adjunct at the hospital therapeutic clinic of I.V. Varvinsky, was elected professor of the department of pathological anatomy and pathological physiology.
Modern medicine is characterized by a constant search for the most objective material criteria for diagnosis and knowledge of the essence of the disease. Among these criteria, morphological acquires exceptional importance as the most reliable.
Modern pathological anatomy widely uses the achievements of other medical and biological disciplines, summarizing the actual data of biochemical, morphological, genetic, pathophysiological and other studies in order to establish patterns relating to the work of a particular organ or system in various diseases.
Thanks to the problems that pathological anatomy is currently solving, it occupies a special place among medical disciplines. On the one hand, pathological anatomy is a theory of medicine, which, by revealing the material substrate of the disease, directly serves clinical practice, on the other hand, it is clinical morphology for diagnosis, which provides the material substrate for the theory of medicine - general and specific human pathology.
Under general pathology understand the most general ones, i.e. characteristic of all diseases, patterns of their occurrence, development and outcomes. Having its roots in the particular manifestations of various diseases and based on these particulars, general pathology simultaneously synthesizes them and gives an idea of the typical processes characteristic of a particular disease.
As a result of the progress of biomedical disciplines (physiology, biochemistry, genetics, immunology) and the rapprochement with them of classical morphology, it became obvious that there was a single material substrate for the manifestations of life activity, including the entire range of levels of organization - from molecular to organismic, and no, even insignificant functional disorders cannot arise and disappear without being reflected in the corresponding structural changes at the molecular or ultrastructural level. Thus, the further progress of general pathology cannot be made dependent on the development of any one discipline or group of them, since general pathology today represents the concentrated experience of all branches of medicine, assessed from a broad biological perspective.
Each of the modern medical and biomedical disciplines makes its contribution to the construction of the theory of medicine. Biochemistry, endocrinology and pharmacology reveal the subtle mechanisms of vital processes at the molecular level; in pathological studies, the laws of general pathology receive a morphological interpretation; pathological physiology gives their functional characteristics; microbiology and virology are the most important sources development of etiological and immunological aspects of general pathology; genetics reveals the secrets of the individuality of the body's reactions and the principles of their intracellular regulation; clinical medicine completes the formulation of the laws of general human pathology on the basis of his own rich experience and the final assessment of the experimental data obtained from the point of view of psychological, social and other factors. So, general pathology implies an approach to the assessment of observed phenomena, which is characterized by their broad medical and biological analysis.
The modern stage of development of medicine is characterized by the fact that disciplines that were previously predominantly or even exclusively experimental (genetics, immunology, biochemistry, endocrinology, pathological physiology, etc.) are becoming equally clinical.
Thus, modern general pathology includes: - generalization of evidence obtained using research methods used in various biomedical disciplines;
Study of typical pathological processes;
Development of problems of etiology, pathogenesis, morphogenesis of human diseases;
Development of philosophical and methodological aspects of biology and medicine (problems of expediency, the relationship between structure and function, part and whole, internal and external, social and biological, determinism, integrity of the organism, nervism, etc.) based on understanding the entire set of facts obtained in various areas medicine; - formation of the theory of medicine in general and the doctrine of disease in particular.
The rapid development of clinical physiology, clinical morphology, clinical immunology, clinical biochemistry and pharmacology, medical genetics, fundamentally new methods of X-ray examination, endoscopy, echography, etc. has enormously enriched our knowledge of the actual details and general patterns of the development of human diseases. The increasingly widespread use of non-invasive research methods (computed tomography, ultrasound diagnostics, endoscopic methods, etc.) makes it possible to visually determine the localization, size and even to a certain extent the nature of the pathological process, which essentially opens the way for the development of intravital pathological anatomy - clinical morphology, which is dedicated to course of private pathological anatomy.
The scope of application of morphological analysis in the clinic is constantly expanding due to the ever-increasing surgical activity and advances in medical technology, as well as due to the improvement of the methodological capabilities of morphology. Improvement medical instruments led to the fact that there are practically no areas of the human body that would be inaccessible to a doctor. At the same time, endoscopy is of particular importance for improving clinical morphology, allowing the clinician to engage in a morphological study of the disease at the macroscopic (organ) level. Endoscopic studies serve the purposes of biopsy, with the help of which the pathologist obtains material for morphological research and becomes a full participant in resolving diagnostic, therapeutic or surgical tactics and prognosis of the disease. Using biopsy material, the pathologist also solves many theoretical issues of pathology. Therefore, the biopsy becomes the main object of research when solving practical and theoretical issues of pathological anatomy.
The methodological capabilities of modern morphology satisfy the pathologist's aspirations for ever-increasing accuracy of morphological analysis of disturbed vital processes and an increasingly complete and accurate functional assessment structural changes. Modern methodological possibilities of morphology are enormous. They make it possible to study pathological processes and diseases at the level of the organism, system, organ, tissue, cell, cellular organelle and macromolecule. These are macroscopic and light-optical (microscopic), electron microscopic, cyto- and histochemical, immunohistochemical and autoradiographic methods. There is a tendency to integrate a number of traditional methods morphological research, as a result of which electron microscopic histochemistry, electron microscopic immunocytochemistry, and electron microscopic autoradiography emerged, which significantly expanded the capabilities of the pathologist in diagnosing and understanding the essence of diseases.
Along with a qualitative assessment of the observed processes and phenomena, it became possible to make a quantitative assessment using the latest methods of morphological analysis. Morphostry gave researchers the opportunity to use electronic technology and mathematics to judge the reliability of the results and the validity of the interpretation of the identified patterns.
Using modern research methods, a pathologist can detect not only morphological changes characteristic of a detailed picture of a particular disease, but also initial changes in diseases clinical manifestations which are still missing due to the consistency of compensatory-adaptive processes [Sarkisov D.S., 1988]. Consequently, the initial changes (preclinical period of the disease) are ahead of their early clinical manifestations ( clinical period illnesses). Therefore, the main guideline in diagnosis initial stages The development of the disease is caused by morphological changes in cells and tissues.
Pathological anatomy, having modern technical and methodological capabilities, is designed to solve problems of both clinical diagnostic and research nature.
The importance of the experimental direction is growing, when both the clinician and the pathologist are looking for answers to complex questions of the etiology and pathogenesis of diseases. The experiment is used primarily to model pathological processes and diseases, with its help new treatment methods are developed and tested. However, morphological data obtained in an experimental disease model must be correlated with similar data from the same disease in humans.
Despite the fact that in recent years in all countries the number of autopsies has been steadily decreasing, pathological examination remains one of the main methods of scientific knowledge of the disease. With its help, an examination of the correctness of diagnosis and treatment is carried out, and the causes of death are established. In this regard, an autopsy as the final stage of diagnosis is necessary not only for the clinician and pathologist, but also for the medical statistician and health care organizer. This method is the basis for scientific research, teaching fundamental and applied medical disciplines, and a school for doctors of any specialty. Analysis of autopsy results plays an important role in solving a number of major scientific and practical problems, for example, the problem of variability, or pathomorphosis, of diseases. The importance of this problem is constantly increasing, since more and more often the clinician and pathologist are faced with the question: where does the pathomorphosis end and where does the pathology of therapy begin?
Pathological anatomy in the 20th century was influenced by the experimental-physiological direction. In contrast to the organolocalistic direction that dominated in the West, in Russia a nosological and functional direction has developed, considering the diseased organism as a whole.
The initiators of this direction were representatives of the Moscow school of pathologists - A. I. Abrikosov (1875-1955), M. A. Skvortsov (1876-1963), V. T. Talalaev (1886-1947), I. V. Davydovsky and others. The same school of pathologists began in 1927 to systematically compare clinical and pathological diagnoses and discuss them together with attending physicians at clinical and anatomical conferences. Subsequently, the conferences were legalized for all hospitals in the USSR; they increased the role of prosectory in diagnosis and stimulated the scientific development of hospital material, strengthening the clinical and anatomical direction.
Pathoanatomical schools, represented by N. N. Anichkov (1885-1964), S. S. Weil and others, carried out a systematic study cardiovascular pathology, reticuloendothelial system, infectious diseases on sectional material and by creating experimental models. Studying pathological changes during infectious diseases devoted to the works of I.V. Davydovsky. V. T. Talalaev studied the histogenesis of rheumatic granuloma (Aschoff-Talalaev granuloma) and created the first clinical and anatomical classification of rheumatism. M.A. Skvortsov and D.D. Lokhov (1892-1958) laid the foundations for the pathological anatomy of childhood diseases.
A. V. Rusakov (1885-1953) et al. worked in the field of bone pathology. A. I. Abrikosov, V. G. Shtefko, A. I. Strukov, A. N. Chistovich and others made a significant contribution to the development of the pathological anatomy of tuberculosis. N. A. Kraevsky, together with the clinician X. X. Vlados, proposed a classification of leukemia. New chapters of pathology were developed - pathological anatomy of combat trauma and radiation sickness, and valuable research was carried out on regional pathology.
Abroad, L. Aschoff (Germany), based on the research of I. I. Mechnikov and V. K. Vysokovich, created the doctrine of the reticuloendothelial system, and was the first to describe an infectious granuloma in rheumatism, which received his name.
The central problem of general pathology, renamed pathological physiology in the USSR (1925), was the problem of reactivity. The ideas of I. I. Mechnikov were most developed in the school of A. A. Bogomolets (1881-1946), who created the doctrine of the role of connective tissue in the reactivity of the body, cytotoxins, aging and life extension. The latter has developed into a separate scientific discipline - gerontology and geriatrics (see).
The methods of angiostomy and organostomy created in the USSR by E. S. London (1868 - 1939) made it possible to study metabolism without disruption neurohumoral regulation I laid the foundation for angiochemistry. The school of A.V. Reprev (1853-1930) investigated the role of endocrine and humoral factors in pathology. S. S. Khalatov (1884-1951), N. N. Anichkov and their students created the doctrine of the pathology of cholesterol metabolism. The school of A.D. Speransky (1888-1961) put forward a theory about the role of neurodystrophic processes in pathology. Representatives of the school of I. P. Pavlov (M. K. Petrova, P. S. Kupalov, A. O. Dolin, etc.) created a new section of pathophysiology - the pathophysiology of higher nervous activity, the doctrine of experimental neuroses. The problems of oxygen starvation, inflammation, fever, shock, and pathophysiology of the cardiovascular system were intensively developed. The pathogenic effects of factors have been studied external environment(electrical injuries, ionizing radiation, low and high atmospheric pressure, etc.).
The term "pathology", made up of two Greek words, means "the science of disease." The discipline, which is currently designated by this term in most countries, has a number of other names: pathological anatomy, pathomorphology, morbid anatomy, anatomical pathology, histopathology, surgical pathology, etc. In domestic medicine, it is customary to call this discipline “pathological anatomy”. Pathological anatomy is a scientific and applied discipline that studies pathological processes and diseases using scientific, mainly microscopic examination changes that occur in cells and tissues.
A pathological process is understood as any disorder of structure and function, and a disease is a combination of one or more pathological processes leading to a disorder normal condition and vital functions of the body.
In the history of the development of pathological anatomy, four periods are distinguished: anatomical (from antiquity to the beginning of the 19th century), microscopic (from the first third of the 19th century to the 50s of the 20th century), ultramicroscopic (after the 50s of the 19th century. ); the modern fourth period of development of pathological anatomy can be characterized as the period of pathological anatomy of a living person.
The opportunity to study pathological changes in the organs of the human body appeared in the 15th-17th centuries. thanks to the emergence and development of scientific anatomy. The most significant role in creating a method of anatomical research, describing the structure of all the most important organs and their relative positions was played in the middle of the 16th century. works by A. Vesalius, G. Fallopius, R. Colombo and B. Eustachius.
Anatomical studies of the second half of the 16th and early 17th centuries. not only strengthened the position of anatomy, but also contributed to the emergence of interest in it among doctors. The philosopher F. Bacon and the anatomist W. Harvey had a significant influence on the development of anatomy during this period.
In 1676, T. Bonet made the first attempt, using significant material (3000 autopsies), to show the existence of a connection between the detected morphological changes and the clinical manifestations of the disease.
In the 17th century The richest anatomical museums appeared in Europe (Leiden), in which pathological anatomical preparations were widely represented.
The most important event in the history of pathological anatomy, which determined its separation into an independent science, was the publication in 1761 of the main work of J.B. Morgani “On the location and causes of diseases identified by the anatomist.”
At the turn of the 18th and 19th centuries. in France, J. Corvisart, R. Laennec, G. Dupuytren, K. Lobstein, J. Boillot, J. Cruvelier widely introduced pathological anatomy into clinical practice, and M. K. Bichat indicated the further path of its development - the study of damage at the tissue level . M.K.Bish's student F.Brousse created a doctrine that rejected the existence of diseases that do not have a material substrate. J. Cruvelier released in 1829-1835. The world's first color atlas on pathological anatomy.
In the middle of the 19th century. The greatest influence on the development of this branch of medicine was exerted by the works of K. Rokitansky, in which he not only presented changes in organs at various stages of the development of diseases, but also clarified the description of pathological changes in many diseases. In 1844, K. Rokitansky founded the Department of Pathological Anatomy at the University of Vienna and created the world's largest pathological anatomical museum. The name of K. Rokitansky is associated with the final separation of pathological anatomy into an independent scientific discipline and medical specialty. The turning point in the development of this discipline was the creation in 1855 by R. Virchow of the theory of cellular pathology.
In Russia, the first attempts to organize autopsy work date back to the 18th century. They are associated with the activities of prominent health care organizers - I. Fisher and P. Z. Kondoidi. These attempts did not produce tangible results due to the low level of development of Russian medicine and the state of medical education, although even at that time autopsies were carried out for control, diagnostic and research purposes.
The formation of pathological anatomy as a scientific discipline began only in the first quarter of the 19th century. and coincided with improvements in the teaching of normal anatomy in universities.
One of the first anatomists to draw students' attention to pathological changes in organs during dissection was E.O. Mukhin.
For the first time, the question of the need to include pathological anatomy among the compulsory teaching subjects at the medical faculty of Moscow University was raised in 1805 by M.Ya. Mudrov in a letter to the university trustee M.N. Muravyov. At the suggestion of Yu.H. Loder, the teaching of pathological anatomy in the form of a course at the department of normal anatomy was reflected in the university charter of 1835. In accordance with this charter, the teaching of an independent course of pathological anatomy was started in 1837 by prof. L.S. Sevruk at the Department of Normal Anatomy. Professors G.I. Sokolsky and A.I. Over began to use the latest pathoanatomical information in teaching therapeutic disciplines, and F.I. Inozemtsev and A.I. Pol - when lecturing on surgery courses.
In 1841, in connection with the creation of a new medical faculty in Kyiv, N.I. Pirogov raised the question of the need to open a department for teaching pathology at the University of St. Vladimir. In accordance with the charter of this university (1842), it was provided for the opening of the department of pathological anatomy and pathological physiology, which began to function in 1845. It was headed by N.I. Kozlov, a student of N.I. Pirogov.
On December 7, 1845, the “Additional Decree on the Medical Faculty of the Imperial Moscow University” was adopted, which provided for the creation of the department of pathological anatomy and pathological physiology. In 1846, Yu. Dietrich, an adjunct of the faculty therapeutic clinic, headed by A.I. Over, was appointed professor of this department. After the death of J. Dietrich, four adjuncts of therapeutic clinics of Moscow University took part in the competition to fill the vacant position - Samson von Gimmelyptern, N.S. Toporov, A.I. Polunin and K.Ya. Mlodzievsky. In May 1849, A.I. Polunin, an adjunct at the hospital therapeutic clinic of I.V. Varvinsky, was elected professor of the department of pathological anatomy and pathological physiology.
For modern medicine characterized by a constant search for the most objective material criteria for diagnosis and knowledge of the essence of the disease. Among these criteria, morphological acquires exceptional importance as the most reliable.
Modern pathological anatomy widely uses the achievements of other medical and biological disciplines, summarizing the actual data of biochemical, morphological, genetic, pathophysiological and other studies in order to establish the patterns of operation of a particular organ and system in various diseases.
Thanks to the problems that pathological anatomy is currently solving, it occupies special place among medical disciplines. On the one hand, pathological anatomy is a theory of medicine, which, by revealing the material substrate of the disease, directly serves clinical practice; on the other hand, it is clinical morphology for diagnosis, which provides the material substrate for the theory of medicine - general and specific human pathology (V.V. Serov, 1982).
By general pathology we mean the most general ones, i.e. the patterns of their occurrence, development and outcomes characteristic of all diseases. Having its roots in the particular manifestations of various diseases and based on these particulars, general pathology simultaneously synthesizes them and gives an idea of the typical processes characteristic of a particular disease. The further progress of general pathology cannot be made dependent on the development of any one discipline or group of them, since general pathology represents the concentrated experience of all branches of medicine, assessed from a broad biological perspective.
Each of the modern medical and biomedical disciplines makes its contribution to the construction of the theory of medicine. Biochemistry, endocrinology and pharmacology reveal the subtle mechanisms of vital processes at the molecular level; in pathological studies, the laws of general pathology receive a morphological interpretation; pathological physiology gives their functional characteristics; microbiology and virology are the most important sources for the development of etiological and immunological aspects of general pathology; genetics reveals the secrets of the individuality of the body's reactions and the principles of their intracellular regulation; clinical medicine completes the formulation of the laws of general human pathology on the basis of its own rich experience and the final assessment of the experimental data obtained from the point of view of psychological, social and other factors.
The modern stage of development of medicine is characterized by the fact that disciplines that were previously predominantly or even exclusively experimental (genetics, immunology, biochemistry, endocrinology, pathological physiology, etc.) are becoming equally clinical.
The rapid development of clinical physiology, clinical morphology, clinical immunology, clinical biochemistry and pharmacology, medical genetics, fundamentally new methods of X-ray examination, endoscopy, echography, etc. has extremely enriched knowledge about the actual details and general patterns of the development of human diseases. The increasingly widespread use of non-invasive research methods (computed tomography, ultrasound diagnostics, endoscopic methods, etc.) makes it possible to visually determine the localization, size and even to a certain extent the nature of the pathological process, which essentially opens the way for the development of intravital pathological anatomy - clinical morphology, which is dedicated to course of private pathological anatomy.
The scope of application of morphological analysis in the clinic is constantly expanding due to the ever-increasing surgical activity and advances in medical technology, as well as due to the improvement of the methodological capabilities of morphology. The improvement of medical instruments has led to the fact that there are practically no areas of the human body that are inaccessible to a doctor. At the same time, endoscopy is of particular importance for improving clinical morphology, allowing the clinician to engage in a morphological study of the disease at the macroscopic (organ) level. Endoscopic examinations also serve the purpose of biopsy, with the help of which the pathologist obtains material for morphological examination and becomes a full participant in resolving issues of diagnosis, therapeutic or surgical tactics and prognosis of the disease. Using biopsy material, the pathologist also solves many theoretical issues of pathology. Therefore, the biopsy becomes the main object of research when solving practical and theoretical issues of pathological anatomy.
The methodological capabilities of modern morphology satisfy the pathologist’s aspirations for ever-increasing accuracy of morphological analysis of disturbed vital processes and increasingly complete and accurate functional assessment structural changes. Modern methodological possibilities of morphology are enormous. They allow the study of pathological processes and diseases at the level of the organism, organ system, organ, tissue, cell, cellular organelle and macromolecule. These are macroscopic and light-optical (microscopic), electron-microscopic, cyto- and histochemical, immunohistochemical and autoradiographic methods. There is a tendency to integrate a number of traditional methods of morphological research, as a result of which electron microscopic histochemistry, electron microscopic immunocytochemistry, and electron microscopic autoradiography emerged, which significantly expanded the capabilities of the pathologist in diagnosing and understanding the essence of diseases.
Along with a qualitative assessment of the observed processes and phenomena, when using the latest methods of morphological analysis, there is the possibility of a quantitative assessment. Morphometry gave researchers the opportunity to use electronic technology and mathematics to judge the reliability of the results and the validity of the interpretation of the identified patterns.
Using modern research methods, a pathologist can detect not only morphological changes characteristic of a detailed picture of a particular disease, but also initial changes in diseases, the clinical manifestations of which are still absent due to the consistency of compensatory-adaptive processes (Sarkisov D.S., 1988). Consequently, the initial changes (preclinical period of the disease) are ahead of their early clinical manifestations (clinical period of the disease). Therefore, the main guideline in diagnosing the initial stages of the disease is the morphological changes in cells and tissues.
Pathological anatomy, having modern technical and methodological capabilities, is designed to solve problems of both clinical diagnostic and research nature.
Despite the fact that in recent years the number of autopsies has been steadily decreasing in all countries, pathological examination remains one of the main methods of scientific knowledge of the disease. With its help, an examination of the correctness of diagnosis and treatment is carried out, and the causes of death are established. In this regard, an autopsy as the final stage of diagnosis is necessary not only for the clinician and pathologist, but also for the medical statistician and health care organizer. This method is the basis for scientific research, teaching fundamental and applied medical disciplines, and a school for doctors of any specialty. Analysis of autopsy results plays an important role in solving a number of major scientific and practical problems, for example, the problem of variability, or pathomorphosis, of diseases.
Objects studied by a pathologist can be divided into three groups: 1) cadaveric material, 2) substrates obtained from patients during their lifetime (organs, tissues and their parts, cells and their parts, secretion products, fluids) and 3) experimental material.
Corpse material. Traditionally, the organs and tissues of deceased corpses are the subject of study during pathological autopsies (autopsies, sections) of persons who died from diseases. Cases of death that did not occur from disease, but as a result of crimes, disasters, accidents or unclear causes, are examined by forensic doctors.
Cadaveric material is studied at the anatomical and histological levels. X-ray, microbiological and biochemical methods are less commonly used. The medical history and all available information are delivered to the pathology department along with the deceased. medical documentation. Before the autopsy, the pathologist is obliged to study all this, and then invite the attending physicians to the autopsy. Clinicians must verify those findings that confirm or refute their ideas about the processes and changes that occurred in the body during the patient’s lifetime. The pathologist records the results of the autopsy in the autopsy report, and indicates the cause of death of the patient in the death certificate, which is then issued to the relatives of the deceased.
Opening. The main purpose of an autopsy is to establish the final diagnosis and causes of death of the patient. The correctness or incorrectness of the clinical diagnosis and the effectiveness of treatment are also assessed. There are criteria for assessing discrepancies between clinical and pathological diagnoses, as well as a classification of the causes of discrepancies. Another goal of autopsy is the mutual enrichment of the scientific and practical experience of clinicians and pathologists. The significance of the sectional work of a pathologist is not only in monitoring the quality of diagnostic and treatment activities of clinicians (this control is complex and is carried out not only by pathologists), but also in the accumulation of statistical and scientific-practical data on diseases and pathological processes.
If sectional work is organized highly professionally and adequately equipped methodologically, then its implementation in full is very expensive. This was one of the reasons for the significant reduction in the number of hospital autopsies in a number of industries. developed countries. A trend towards a reduction in the number of autopsies has also emerged in Russia.
Material taken during the patient's lifetime. A much larger volume of a pathologist’s work is occupied by microscopic study of material obtained for diagnostic purposes during the patient’s lifetime. Most often, such material comes from operating clinicians: surgeons, gynecologists, urologists, otorhinolaryngologists, ophthalmologists, etc. The diagnostic role of the pathologist here is great, and his conclusion often determines the formulation of the clinical diagnosis.
Histological examination. This study involves the operating room and biopsy materials. The pathologist is required to provide histological confirmation (clarification) of the diagnosis. In both cases, immediate fixation of the removed tissue is important. Even not very long-term keeping of removed pieces or substrates in air, water or saline solution can lead to irreversible, artificially induced changes in the material, which will complicate or exclude the correct histological diagnosis.
Pieces of no more than 1 cm in diameter are cut out of the fixed material using a sharp razor, then they are placed in special cassettes and placed in machines for histological processing.
Histological sections 5-10 microns thick are glued onto glass slides, deparaffinized, stained in one way or another, and then placed in optically transparent media under a coverslip.
For urgent biopsies, often performed during extensive surgical interventions In order to quickly obtain a histological diagnosis, the tissue is frozen and cut on a cryostat or freezing microtome. Frozen sections are usually thicker than paraffin sections, but they are useful for preliminary diagnosis. A cryostat and freezing microtome are used to preserve alcohol-soluble and some other tissue components that are important for diagnosis (for example, fat).
For routine diagnosis, universal histological staining of sections with hematoxylin and eosin is widely used. Tinctorial, i.e. The coloring properties of hematoxylin are realized in a slightly alkaline medium, and structures colored blue or dark blue with this dye are usually called basophilic. These include cell nuclei, lime salt deposits and bacterial colonies. Some types of mucus can produce mild basophilia. Eosin, on the contrary, at a pH less than 7 colors the so-called oxyphilic components pink-red or red. These include the cytoplasm of cells, fibers, red blood cells, protein masses and most types of mucus. Van Gieson picrofuchsin staining is very often used, electively, i.e. selectively, staining the collagen fibers of the connective tissue red, while other structures become yellow or greenish-yellow. There are also a variety of histological stains to identify specific tissue components or pathological substrates.
Cytological examination. It is carried out on smears made from the contents of hollow or tubular organs, as well as on impression preparations, punctures and aspirates (aspiration punctates, sucked out with a syringe). Smears are often made from material from swabs from the walls of organs, which makes it possible to capture cells that are in the process of natural or pathological desquamation (desquamation, exfoliation), for example, from the cervix. A more active intervention is scraping from the walls of organs. If the scraping material is abundant, it is processed using histological techniques. In particular, this is done with diagnostic endometrial scrapings. With scanty scrapings, the material is sent for cytological processing. Often, preparations are made from sputum, mucus, tissue trains and sediments in liquids. Precipitates can be obtained after centrifugation of suspensions.
Cytological material is usually fixed directly on a glass slide, often during staining. The most popular stains are: azure-eosin (its tincgorial properties are close to hematoxylin and eosin) or Bismarck-Brown according to Papanicolaou.
Immunohistochemical study. For some pathological conditions, especially tumors, it can be difficult and even impossible to determine the type of tissue or its origin (histogenesis) using histo- or cytological stains. Meanwhile, such verification is important for diagnosis and prognosis. Therefore, various additional methodological approaches are used. One of them is the immunohistochemical method. In this method, solutions with antibodies to the desired antigens are applied to histo- or cytological preparations: tumor, viral, microbial, autoantigens, etc. Antigens are not visible with conventional histological stains of tissues. Antibodies in serums carry a label: either a fluorochrome, i.e. a dye that glows in a dark field (in other words, gives fluorescence), or a dyeing enzyme. If the desired antigen is present in the tissues or cells being studied, then the resulting antigen-antibody complex plus a marker will accurately indicate its location, quantity, and will help study some of its properties.
Immunofluorescence is most often used when studying sections prepared in a cryostat or on a freezing microtome, as well as when studying cytological preparations. Sera with antibodies, so-called antisera, are used, most often conjugated with such a reliable fluorochrome as fluorescein isothiocyanate. Most Popular indirect method, allowing the detection of antigens using a double reaction with antibodies.
The immunoperoxidase method is even more common. The antibodies of the dye serum do not carry a fluorochrome, but an enzyme - horseradish peroxidase, or less often another enzyme, for example, alkaline phosphatase. There are several variants of this method. The two most commonly used are the peroxidase-antiperoxidase method (PAP method) and the avidin-biotin complex method (ABC method).
With the PAP method, the chain of intermediate antibodies that bind the enzyme to the antigen is slightly longer than with the indirect immunofluorescence method. Enzymatic, i.e. The peroxidase antibody binds to the primary antibody already present on the antigen through another bridging antibody.
With the avidin-biotin method primary antibody, located on the antigen and labeled with biotin, binds to the PAP complex through an intermediate antibody labeled with avidin. Both proteins, avidin and biotin, dramatically increase the quality of the reaction, so the ABC method is considered more sensitive.
For immunohistochemical reactions, 2 types of antibodies are used: poly- and monoclonal. The former are obtained from antisera from immunized rabbits. Monoclonal antibodies are obtained in tissue culture or from ascitic fluid obtained from abdominal cavity laboratory animals. Monoclonal antibodies are absolutely specific for the antigen and do not cause cross-reactivity.
The popularity of the immunoperoxidase method is mainly due to its simplicity and accessibility. There are many commercial kits of sera to various tissue- or tumor-specific antigens, called markers. The benefits of using immunoperoxidase reactions are explained by their high sensitivity (compared to immunofluorescence, the PAP method is 1000 times more sensitive, and the ABC method is 10,000 times more sensitive), relative stability, and the possibility of using some reactions on dewaxed sections that have undergone both fixation and passage through alcohols.
Methods of molecular biology. In well-equipped pathology departments and research institutes, molecular biology methods are used for intravital diagnostics: flow cytometry and in situ hybridization techniques, i.e. in place, on a histological section. The first method is necessary for quantitative analysis of DNA content in tumor cells. For this purpose, the piece of unfixed tissue under study is subjected to disaggregation with the help of enzymes, i.e. separation and crushing into individual cells. Then, in a special installation, a stream of a suspension of isolated cells 1 cell thick, surrounded by an enveloping liquid, passes through a reading laser beam.
Using in situ hybridization, the combination of genetic material (DNA fragments, genes) is achieved in vitro on the basis of complementarity, i.e. mutual correspondence, for example, of purine or pyrimidine bases in nucleic acids. This method is used mainly in three areas of pathology: to identify microbes or viruses found in tissues or fluids by genome; to study the genome during its congenital disorders; in the diagnosis of tumors, in particular, for the recognition of viral oncogenes. There are many modifications of the method.
Polymerase is very popular chain reaction(PCR), which is carried out directly on histological sections. First, the DNA being tested is denatured, i.e. separating its two spiral threads and obtaining one of them in an isolated state. Then another foreign strand (usually RNA) labeled with a fluorochrome or PAP complex is layered. The molecular structure of this thread, i.e. the sequence of its bases is known. If there is complementarity with the test thread, then the staining reaction on the histological specimen is positive, and the structure of this thread becomes known.
Chromosome research. In many modern pathology departments and research institutes, chromosomal analysis is carried out, which makes it possible to determine deviations in the genetic apparatus (genome) of cells that are congenital or acquired.
This analysis is of particular importance when recognizing and studying tumors, various variants of which are accompanied by very specific marker rearrangements or chromosome aberrations. To do this, the tissue taken intravitally is cultured, i.e. grown on artificial media. This method of cultivation makes it possible, by reseeding and selecting cells, to obtain a culture of cells of the same tissue type and even one clone, i.e. line derived from a single stem cell.
The main stages of chromosomal analysis using the example of studying blood lymphocytes are as follows. Phytohemagglutinin is added to the culture of heparinized blood (heparin is an anticoagulant), stimulating T-lymphocytes to transform into blasts (less mature forms capable of mitosis and division). After 2-3 days of incubation, colchicine is added to the culture to delay mitosis at the metaphase stage in dividing lymphocytes. It is in the megaphase that the chromosomes seem to spread out, which is convenient for study. The cells are then transferred to a glass slide, fixed and stained, most often using the Giemsa method. As a result, light (uncolored) and dark (colored) bands are detected in each pair of chromosomes, which is why the method is called chromosome backing. The arrangement of bands in a normal karyotype (set of chromosomes) is highly specific for each pair of chromosomes, and banding diagrams (maps) are normally well known.
Chromosomal analysis is an economically expensive method and is therefore rarely used.
Electron microscopy. During diagnostic studies Electron microscopy is often used on material taken during the patient’s lifetime: transmission (in a transmitted beam, similar to light-optical microscopy) and scanning (removing the surface relief). The first is used more often, especially for studying the details of cell structure in ultrathin sections of tissue, identifying microbes, viruses, deposits of immune complexes, etc. Ultrastructural research is very expensive, but is often used for diagnostic and scientific purposes.
Experimental material. When examining tissue taken during the life or after the death of a sick person, the pathologist observes changes at the time the tissue is removed. What happened before and could have happened after remains unknown. Experiment with sufficient quantity laboratory animals (white mice, white rats, guinea pigs, rabbits, dogs, monkeys, etc.) allows you to model and study diseases and pathological processes at any stage of their development.
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