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ЗмістTraining discipline structure
Module 1 “General pathologic processes and tumor growth morphology” Notional modules 4
Tasks of pathologic morphology
Accessory aids to student’s self-work
Basic matters for self-work
Practical class 1-2
Causes of metabolism products abnormal uptake
Endocrine and nervous regulation of trophism disorders.
Metabolism products abnormal uptake classification
Morphology of proteins abnormal uptake (proteinosis)
At hyaline-drop proteinosis
Morphology of lipids pathological uptake (lipidosis)
Neutral fat local uptake
General decrease of adipose tissue
This textbook was written in conformance with new training program in pathological morphology for higher educational establishments of Ukraine which was worked out based on European credit-transfer system principles.
The authors didn’t set an object to develop comprehensive textbook. The aim of the book is clearly and easily assist student to acquire habits of synthetic generalization of pathologic processes demonstration and their interpretation in cause-effect correlations.
Textbook is structured by modules. Its first part covers one module– general pathologic processes and tumors growth. Notional modules include theoretical knowledge base, self-control system and artwork of pathologic processes macroscopic and microscopic manifestations, guiding student to reach specific objects in creative way.
Training plan description in “Pathological morphology” discipline during general pathologic processes and tumors growth morphology study
processes and tumors growth
Notional module 1
Introduction. Morphology of cells and tissues injury
Lecturers – 4 hours
Practical classes – 8 hours
Student’s self-work – 7 hours
Form of student’s individual self-work – thesis or library-research papers
Theme 1. Subject and tasks of pathologic morphology. Methods of pathologic morphology investigations. Main stages of pathologic morphology development.
Basic matters for self-training:
Pathologic morphology is a science studying structural (material) fundamentals of diseases to comprehend material foundations of medical science as well as profound study of disease clinical picture with latter utilization of acquired knowledge in the practical work of physician.
- to study cell pathology;
- to study general pathologic processes, aggregation of which determine morphologic manifestation of these of those diseases;
- to study etiology, pathogenesis and morphology of diseases at different stages of their development (morphogenesis) structural basis of recovery, complications and consequences;
- to study morphology and mechanisms of organism adaptation and compensation processes in response to pathogenic factors and environment conditions influence;
- to study pathomorphism of diseases, originating in connection with living conditions of the person, which are changing, as well as the result of various therapeutic actions (pathology of therapy);
- to study postmortem examination service organization.
Pathologic morphology as fundamental and clinical field of medicine. Clinical-anatomic orientation of national pathologic morphology. Principle structure and function unity.
Disease morphologic and clinical manifestation comparison at every stage of disease onset.
Clinical-anatomy analysis, synthetic generalization of diagnostic signs of diseases and their interpretation in cause-effect correlations.
Methods of pathologic morphology investigations are autopsy, biopsy, surgery material study, experimental modeling.
Modern methods of biopsy material study. Biopsy: types, meaning for diseases early recognition and treatment, benign and malignant tumors identification, surgery feasibility and scope determination, and patient’s living prognosis.
Various studies of diseases’ structural fundamentals: organism, system, tissue, cell, cubcellular, molecular.
Post mortem aim, specific matters of early and planned autopsy of died patient. Autopsy importance to clarify causes and mechanisms of patients’ death, analysis of the quality of diseases diagnostic in patients’ lifetime and quality of patients’ treatment.
Characteristics of pathologic morphology development. Contribution of D.Morganyi, K.Rokytanskyy, R.Vyrkhov in international pathologic morphology development.
Stages of national pathologic morphology formation.
Pathologic anatomy being fundamental medical-biology science is at the meeting point of medical theory and practice. Main assignment of pathology anatomy service is lifetime and posthumous diagnostic of diseases, study of etiology, pathogenesis and tanatogenesis of the most widespread diseases, control of clinical diagnostic quality and therapeutic process effectiveness as well as physicians’ professional advanced training.
Basic methods of diseases posthumous and lifetime diagnostic
Basic methods of diseases posthumous diagnostic are macroscopic (autopsy) and microscopic (necropsy), lifetime diagnostic are microscopic (biopsy, cytology) and experiment. Accessory methods are as follows: biological (bacteriologic, virologic, serologic, hematological, tissue culture method), chemical (histochemical, immunohystochemical, atomic absorptiometry, quantitative analysis, qualitative analysis, biochemical), physical (hystoautoradiography, roentgenography, roentenostructural analysis, ultrasonic diagnostics).
Autopsy (from Greek – to see somebody, to see in own eyes). Function :
- scientific-cognitive process development. During autopsy not only last terminal stage of disease is fixed, but also morpho-fuctional changes dynamics is clarified.
For example, stages of cardiac (nutmeg, portal, small nodular) liver cirrhosis or secondary tuberculosis. Based on acquired knowledge new classifications of diseases are developed and old ones are updated;
- control of treatment-prophylactic facility work quality. It determines non-conformity or conformity of clinical and postmortem diagnosis, cause of death. Due to study of latter the efforts of medical personnel can be concentrated to eliminate them further on. For example, it was revealed that pulmonary edema is often registered in cardio section as direct cause of death. By the way of analysis the cause of incorrect diagnosis can be found. It could be poor qualification of physician, insufficient reanimation measures or ungrounded utilization of medicines, etc. Autopsy is used to analyze new diagnostic procedures, medicines, surgery methods of treatment effectiveness determination;
- contagious diseases detection and prophylaxis, especially those subject to quarantine;
- students and practicing physicians training. Not in vain on the gamble of Sorbonne (Paris) prosectorium in XIV century it was written: "Here is the place where mors trains to live". It’s analysis of diagnostic, treatment faults should be mandatory for every physician. M. Pyrogov mentioned "Medical mis-actions is a science of special importance ". Definition of medical error was given by I.Davydovskyi "This is honest mistake of physician and, in case this mistake happened, there is no other way to improve except by own mistakes investigation”. Besides above said, there is no better science than to see changes of organs and systems gross observed. That’s owing to autopsy excellent anatomic atlases of Leonardo da Vinci, Rembrandt, M.Pyrogov appeared;
- finding new diseases, their aetiology and path morphogenesis, for example, presentation of familial hypertrophic cardiomyopthy, a number of hereditary and congenital diseases, prion diseases, B type chronic gastritis, etc.
Necropsy (from Greek пекгоз - dead and орзіз - to look) are done to confirm or deny revealed gross manifestation of pathologic processes on cellular and subcellular levels.
Biopsy (from Greek Ьіоз - life and орзіз – to look) is microscopic examination of alive human beings’ tissues. Biopsy could be urgent (tissues examination during surgery), as well as planned to clarify diagnosis or under preventive examinations. To carry out urgent examination the method of frozen sections or replicas is used. Last one is used for cytological examinations. Main purpose of biopsies is to make out accurate intravital diagnosis. Material for biopsy is tissues extracted in surgical way and for cytology – secrets (urine, sputum, blenna, mammary secretions, etc.), replicas from tissues and swabs as well as cells acquired by aspiration from mammary glands, liver, lymph glands, lungs, pancreatic glans, etc. Utilizing auxiliary research methods pathomorphological changes on subcellular and molecular levels are determined. Thus, with electron microscopic methods histogenesis of a number of tumors is revealed, with immunehistochemical methods – hormones, receptors, immunoglobulins, antigenic proteins, ferments, karyogens and with histochemical methods – various classes of proteins, fats, carbohydrates, metals and ferments.
Experiment is quite rarely used in pathoanatomy. However it is known that some illnesses existence can be proved utilizing research model. En example could be guinea-pigs infection with urine of kidneys ill with tuberculosis.
Nowadays іп situ hybridization is used more and more widely. The essence of hybridization technology is based on the fact that nucleic acid bases are complementary to each other in one chain. Utilization of marked test makes it possible to find complementary nucleic acids in the cells. Latter could be a portion of native dezoxyribonucleic acid (DNA) cell, a portion of ribonucleic acid, bearing information from certain genes or a portion of virus genome. In such a way, it could be found morphologically in a cell where target is localized or if target is absent. Utilizing above named method it is possible to determine presence of papilloma virus, cytomegalovirus, virus of herpes.
Practical activity of pathologist on modern stage
On the modern stage of medicine development considerable changes in illnesses clinical pictures, morphology and consequences, namely pathomorphism, are seen caused by wide introduction of new hormonal medicines, antibiotics, drug-mediators into physicians’ practice as well as by environment contamination with xenia-biotics. It is also caused by new reanimation measures, artificial blood circulation, mechanical ventilation and organs transplantation introduction into medical practice. More often doctor sees combination of several severe illnesses. He/she also is faced with “therapy pathology” problem, meaning disease states caused by medical interventions.
Above named changes in medical practice complicated anatomist to define various processes pathogenesis, especially – genesis. To solve these problems the practice of mutual with hospital physicians discussion found morphologic facts is widely introduced at the moment. Besides that subspecialty of pathologists are widely spread. Thus anatomists working in Oncology Dispensaries, Tuberculosis Dispensaries, Cardiac Dispensaries, Infection hospitals, etc. become narrowly focused specialists. Quite often their work in these establishments narrows down to small range of diseases interpretation. This relates to scientific-research institutes and laboratories in which these specialists carry out ancillary work ordered, formally describe found morphological changes and give these descriptions to the others to analyze and interpret. It often occurs in laboratories where experiments are carried out, for example, to study new medicines effect. In these circumstances anatomist becomes morphologist, specialist with narrow range of cogitation, restricted by his/her methods data and clinical field of medical establishment he works at.
As practice shows the most part of his/her working hours anatomist spends for life-time diagnostics of diseases. However, utilizing such forms of biopsy as puncture, aspiration, trepanobiopsy, etc. as well as cytology, chemical and physical methods, anatomist controls the course of curative process and disease dynamics in general. In our days his/her services are asked by surgeons, oncologists, gastroenterologists, renal pathologists, cardiologists. It’s just study of kidneys, liver, skin biopsy made it possible to extend imagination of glomerulopathies, viral hepatitis, rheumatic diseases pathogenesis, to define their clinicopathologic forms.
In our days anatomist is not limited with pathologic process affirmation only, more and more often he/she gives definition of its stages, prognosis. Whereas earlier it was enough to diagnose only presence of cancer or sarcoma, this diagnosis is not complete now. Anatomist is required to differentiate accurately histological accessory of tumor, tumor maturity stage as the character of medical intervention depends on that. It is this to cause wide introduction of histochemical, electron microscope, morphometric, immunological morphological investigation.
Clinical-laboratory data is more often used for biopsy interpretation as it would be incorrect to use widely ancillary methods but evaluate pathologic process only by morphology data. As it is known, sometimes biopsy is taken in non-standard location, so morphologic diagnosis can differ from clinical one. In such a case the results are discussed by clinicians who are interested and have equal rights participants of diagnosis process.
Theme 2 Elements of cell ultrastructural pathology. Cell-matrix interactions. Cellular and extracellular mechanisms of trophism regulation. Alteration: intracellular pathology
Theme topicality: Alteration or injury is the most wide spread reaction of living tissues as an answer to pathogenic action. Its various levels morphologic manifestations exists under each disease, and degree of injury intensity determines functional ability of organs and tissues. Knowledge of alteration structural manifestations gives capability to evaluate properly the dynamics of diseases course and to foresee their consequences.
The aim is to study alteration reasons, morphologic characteristic at ultrasonic level and its significance in the diseases development, clinical course and consequences.
^ 1) To know reasons, morphology and consequences of intracellular pathology.
2) To learn to identify alteration manifestations on intracellular level.
3) To be able to compare alteration manifestations on electron-diffraction patterns under various intracellular structures injury.
Cell is elementary living system, able to exchange with environment.
Modern concept of cellular organelles structure and functions. Nucleus: structural-functional characteristics. Plasmolemma: structure, features, injury consequences. Cytoskeleton and its components.
Cell pathology as integrative idea. Cell nucleus pathology. Mitosis pathology, chromosomal aberrations and chromosome diseases. Stereotyped injuries of ultructructures as an answer to various impacts. Cell membranes pathologic modifications and cells modifications under plasmolemma injury. Pathologic modifications of endoplasmic reticulum. Golgi complex pathologic modifications. Pathologic modifications of mitochondrion. Pathologic modifications of lysosomes. Pathologic modifications of peroxisomes. Pathologic modifications of cytoskeleton (microfilaments, microtubules). Cells movement and its role in pathology. Specific modifications of ultrastructures: receptors’ “diseases”, lysosomes, mitochondrial, peroxisomal “ diseases”.
Cell-matrix interactions. Cellular and extracellular regulation mechanisms.
Epithelial tissue, basal membrane, conjunctive tissue: morphologic characteristic, basic functions.
Cellular adhesion. Information process in the course of intercellular interaction (endocrine, paracrine and autocrine regulation). Cellular junctions pathology.
Mechanisms of signal transduction, signals transmission through intracellular receptors. Cytokines: classification, sources, functions.
І Accessory material for self-work
Pathologic process is natural organism response in reply to injury factor. Various in its origin the latter is able to act directly or indirectly (through humoral or reflex influence) on cells and tissues, they reply this influence with stereotyped reactions: alteration, blood supply disturbance, compensation and adaptation, inflammation, give tumors growth. In some cases these are superficial and reversible changes and in the other cases they are deep and irreversible. Any of them could be a constituent of general pathologic process. It is established that in most cases organism reacts injury with adaptive, defense and compensatory reactions. In case of their insufficiency diseases is developed quite often. For example, inflammation as defense-adaptive reaction occurs as a reply to alteration, cause by mechanical trauma, temperature, chemical agents, infection agents and other injury factors. Simultaneously alteration and blood supply disturbance are constituent elements of inflammation, which often is main manifestation of disease and disease often develops in case of their insufficiency.
Alteration (from Lat. alteratio – change) or injury are modifications of cells structure, intercellular substances, tissues and organs expressed in their disfunctions. The causes of alteration are various. Factors can influence cellular and tissue structures directly (trauma mechanical, thermal, electrical, barometric, toxins of endogenous and exogenous origin) as well as indirectly through humoral (thyrotoxicosis, allergy), or reflex (vasospasms causing hypoxia) influences. Character and degree of alteration depends on pathogenic factor strength and nature as well as on functional features of the organ and tissue. Injury mostly occurs in functionally active parenchymatous structures (heart, cerebrum, liver, kidneys) or on histion level. In some cases superficial and reversible changes of intracellular ultrastructures occur and in the other cases they are deep and irreversible and can end with specific cells, whole organs dying off or even whole organism death. Alteration includes dystrophy and necrosis which as a rule are consequent stages of injury and can develop on ultrastructure and cell levels.
Is manifested with injury of plasmolemma, nucleus, mitochondrio, granular and granular endoplasmic reticulum, Golgi apparatus, lysosomes, microfilaments, cytoplasm, etc.
Plasmolemma pathology causes active membrane transport disturbance, water-electrolytic metabolism imbalance, cells swelling and edema. In certain cases under plasma membrane injury some substances delve into cytoplasm and various types of cellular degenerations occurs. Complete injury of Plasmolemma causes cell necrosis.
Membrane injuries conditionally can be distributed into:
Transport, functional-metabolic, structural
Plasma membranes pathology variations:
Nucleus pathology variations:
Mitochondrion pathology variations:
Granular and agranular endoplasmic reticulum pathology variations:
Golgi apparatus pathology variations:
Lysosomes pathology variations:
Is manifested with their number increase under neoplastic growth, wounds incarnation, liver diseases, alcoholism, cholestasis, cardiomyopathies, etc..
Theme 3 Morphology of cells and tissues reversible and irreversible injury. Intracellular and extracellular accumulation (uptake) of proteins, hydrocarbons and lipids. (Parenchimatous and mesenchimal dystrophies)
Theme topicality: cells and tissues reversible and irreversible injury attributes to general pathologic processes. This injury is often observed under tissue or cellular metabolism disturbance, under cell metabolism substances accumulation or accumulation of endogenous or exogenous pathologic products and is manifested with structural-morphologic changes. These injuries occurs in cells or tissues under various diseases, so knowledge of this theme is necessary for correct understanding and satisfactory learn of the other subsections of general and special anatomical pathology.
Aim: to learn etiology, mechanisms of development, morphologic phenomenon and consequences of cells and tissues reversible and irreversible changes.
1. To know varieties of intracellular uptakes, their development mechanisms.
2. To learn the causes, patho- and morphogenesis, morphologic phenomenon, consequences of proteins, glycogens, lipids accumulation in cells and tissues.
3. To know essence of extracellular uptakes, to be able to diagnose hyaline changes in the cells and tissues.
Basic matters for self-work:
Intracellular accumulations (uptakes): definitions, development mechanisms. Varieties: cell metabolism normal products accumulation, accumulation of pathologic products (exogenous or endogenous).
Protein uptakes (proteinosis): causes, pathogenesis and morphogenesis, morphologic characteristics and methods of diagnosis, clinical symptoms and syndromes, consequences.
Glycogen uptakes (glycogenosis): causes, pathogenesis and morphogenesis, morphological characteristics and diagnosis methods, clinical manifestations, consequences. Acquired and congenital glycogen uptakes.
Lipids uptakes (lipidosis): causes, pathogenesis and morphogenesis, clinical-morphological characteristics, diagnosis methods, consequences. Steatosis. Fatty modifications of myocardium, liver, kidneys. Cholesterol and its esters. Acquired and congenital lipids metabolism disturbances, morphological characteristics.
Extracellular uptakes. Hyaline modifications (degenerations). Intracellular and extracellular hyaline: morphogenesis, morphological characteristics. Hyaline modifications under various pathologic conditions.
І Accessory material for selfwork
Cells and tissue reversible changes occurs in the result of tissue or cell metabolism disturbance and are accompanied with these substances (proteins, fats, hydrocarbons) which exists as norm intracellular or tissue uptakes and appearance of those pathological which do not exist in the norm. These changes are named metabolic products pathologic uptakes or dystrophies (from Lat. dys – disturbance, trophe – nutrition). Intracellular uptake of substances causes parenhymatous degenerations development. Parenhymatous degenerations occurs mostly in highly specialized cells of parenhymatous organs (kidneys, liver, heart, cerebrum, etc.). Acquired or congenital fermentopathies underlie parenhymatous degenerations development. These fermentopathies make a big group of storage diseases or thesaurismoses. Latter contain a big group of storage diseases or thesaurismoses.
1 Cell pathology. Cells are not able to utilize substances as energy or plastic material or release them. This is caused mostly by cells structure injury with various factors, sometimes by congenital or acquired ferments pathology, which participate in metabolism (fermentopathies).
2 Function disturbance of transport systems, providing both substances supply to tissues and cells and metabolism products excretion. It is often observed under cardiovascular collapse and pulmonary insufficiency.
Mechanisms of metabolism products abnormal uptake Infiltration is excessive penetration of metabolism products from blood into cells and intercellular substance with their subsequent uptake due to ferment system, providing their metabolism, insufficiency. Substances metabolism products abnormal uptake by way of infiltration is observed in liver, kidneys, aorta wall.
Decomposition (phanerosis) occurs under cell and intercellular substance ultrastructures destruction due to intoxication, hypoxia or other reasons. Ultrastructures membranes are made of proteins, fats and hydrocarbons, so under their destruction these substances are accumulated and stored in cells.
Distored synthesis is synthesis of those substances in cells and tissues which are not observed in them as a norm. As an example, it’s glycogen synthesis in nephron tubules epithelium under diabetes mellitus, alcohol hyaline synthesis in hepatocytes.
Transformation is the creation of one kind of metabolism products from intermediate disintegration products, which should be utilized for proteins, fats and hydrocarbons synthesis. For example, it’s fats and hydrocarbons components transformation into proteins under starvation, fats and hydrocarbons components transformation
into glycogen under diabetes mellitus.
Classification by the kind of metabolism disturbance prevail:
a) protein, b) fat, c) hydrocarbon, d) mineral
By pathologic process localization:
a) parenchymatous (modifications in the organs parenchymatous cells - cardiomyocytes, hepatocytes, ganglionic cells of cerebrum, etc.);
b) stromal-vascular (modifications in organs stroma);
c) mixed (changes in parenchyma and stroma).
Depending on genetic factors influence:
a) congenital, b) acquired.
By process spread:
a) general, b) local.
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