Introduction to concepts of pathology. Characteristics and classification of diseases. Introduction to general pathology Markéta Hermanová Pathology nGeneral pathology: Scientific study of disease n causes (etiology) n mechanisms of development (pathogenesis) n structural changes in diseases (morphology) n clinical consequences of changes n nPathology in clinical practice (diagnostic pathology) -diagnosis of the disease based on the examination of surgically removed tissue specimens (histopathology, examination of biopsies) and cytological specimens (cytolopathology): 98 % -autopsies (necropsies – postmortem examinations): 2 %* - n *in Czech Republic majority of autopsies performed in forensic medicine/pathology dpt, n only minority of autopsies performed in dpt of pathology/anatomical pathology n n n n Who is a pathologist? nPhysicians specialized in the diagnosis and characterization of disease based on examination of tissues (biopsies) and cytological specimens (pleural and pericardial fluid, ascites (from peritoneal cavity), urine, cervical smears, blood, …..) n nSpecial focus on histopathological diagnosis of oncological diseases n nClinico-pathological cooperation n Tissue biopsy: how to obtain the tissue for histopathological examination? nCurretage nFluid aspiration nFine needle aspiration nCore needle biopsy nDermal punch nEndoscopy nStereotactic biopsy nSurgical excision and resection Resection specimen - rectum Formalin-fixed tissue 3-4.jpg 3-3.jpg Evaluation of surgical resection specimens: brain resection specimen Temporal pole resection specimen Amygdalohippocampal complex 10% neutral buffered formalin, 24 hours, formalin fixed paraffin embedded tissues, paraffin sections Remaining unfixed tissue slices snap frozen in liquid nitrogen – molecular biology and genetics Gross inspection, measuring, cutting representative tissue slices, perpendicular to the cortical surface 3-1.jpg 3-2.jpg Techniques of pathology nGross pathology nLight microscopy nEnzyme histochemistry nImmunohistochemistry and immunofluorescence nElectron microscopy nMolecular pathology and genetics n n+ biochemical, haematological and microbiological techniques, cell cultures (in clinical pathology) n Focal cortical dysplasia: maldevelopment of cortex histopathological examination 5258-08-IIa-100x 8389-08-02 sel 4979-08-NF NF-01 Common staining methods: hematoxylin-eosin Immunohistochemistry: detecting antigens (e.g. proteins) in a tissue section using antibodies with subsequent visualisation of this binding (Ag/Ab) Autopsy (= necropsy, postmortem examination) nDetermining the cause of death n nAudit of the accuracy of clinical diagnosis n nEducation of undergraduates and postgraduates n nResearch into the causes and mechanisms of he disease n nGathering accurate statistics about disease incidence Death nModes of death differ according to the ultimate cause n nCauses of death: n - natural (due to disease) n - unnatural (due to accident, homicide etc.) n Common modes of death Common cause of death Mode of death Common cause Clinical manifestation Cardiac arrest and dysrhythmia Ischaemic heart disease Pulmonary embolism Sudden and often unexpected death. Shock Haemorrhage Toxaemia due to infection Profound hypotension and tachycardia Hypotension, tachycardia and pyrexia Respiratory failure Emphysema, pneumonia, asthma Cyanosis, tachypnoea Stroke Raised intracranial pressure Cerebral infarction Localised neurological defect, coma Renal failure Chronic renal failure Low renal output, high blood urea and creatinine Liver failure Acute hepatitis, decompensated cirrhosis, paracetamol poisoning Jaundice, coma, bleeding Learning pathology nGeneral pathology -The mechanisms and characteristics of the principal types of disease proces (e.g. inflammation, tumours, degenerations,…) - nSystemic pathology -The descriptions of specific diseases affecting individual organs or organ systems (e.g. GIT, respiratory tract, brain, muscles…) - Who is your teacher? nProf. MUDr. Markéta Hermanová, Ph.D. nmarketa.hermanova@fnusa.cz n+420543183218 n nMUDr. Víta Žampachová nvita.zampachova@fnusa.cz n+420543183231 n n n Recommended literature for the exam …and especially content of lectures! …the questions for the exam will strictly follow the lectures.. Characteristics of the disease nAetiology (cause: genetic, multifactorial, environmental) n nPathogenesis (mechanism: inflammation, degeneration, carcinogenesis, immune reaction) n nPathological and clinical manifestation n (morphological, functional, clinical) n nComplications and sequelae n nPrognosis (or outcome) n nEpidemiology (or incidence, population distribution) Nomenclature of the disease nPrimary and secondary -primary: without evident antecedent cause (=essential, idiopathic, cryptogenic) -secondary: complication or manifestation of some underlying disease -primary and secondary also used to distinguish between initial and subsequent stages of a disease n nAcute, subacute and chronic -describing the dynamics of the disease - nBenign and malignant -describing their likely outcome -benign tumors vs malignant tumors -benign hypertension vs malignant hypertension Prefixes Prefix Meaning Example Ana- Absence Anaplasia Dys- Disordered Dysplasia Hyper- Excess over normal Hyperthyreoidism Hypo- Defficiency below normal Hypothyreoidism Meta- Change from one state to another Metaplasia Neo- New Neoplasia Suffixes suffix meaning example -itis Inflammatory process Appendicitis -oma Tumour Carcinoma, adenoma -osis State or condition, not necessarily pathological Osteoarthrosis -oid Bearing the resemlance Rheumatoid -penia Lack of Thrombocytopenia -cytosis Increased number of cells Leukocytosis -ectasis Dilatation Bronchiectasis -plasia Disorder of growth Hyperplasia -opathy Abnormal state lacking specific characteristics Lymphadenopathy General classification of diseases Mode of acquisition Pathogenetic classification Subclassification Example Congenital Genetic Inheritid Cystic fibrosis Spontaneous Down´s syndrome Nongenetic Environmental Rubella-assoc. malformation Accidental Cerebral palsy due to hypoxia at birth Aquired Inflammation Acute Accute apendicitis Chronic Tuberculosis Growth disorders Neoplastic Lung cancer Nonneoplastic Benign prostatic hyperplasia Injury Kinetic energy Bone fracture Chemicals, etc. Aspirin induced gastric ulcer Haemodynamic Shock Haemorrhagic shock Occlusive lesions Ischaemic heart disease Disordered immunity Immunodeficiency AIDS Autoimmune diseases, allergy Grave´s thyreoiditis Metabolic Diabetes mellitus Degenerative Osteoarthritis Causes of disease nGenetic -Inherited or prenatally acquired defects of genes - nMultifactorial -Interaction between genetic and environmental factors - nEnviromental -No genetic component to risk of disease n n Genetic factors Environmental factors Cystic fibrosis Traumatic head injury Diabetes Breast cancer General pathology Mechanisms of cell death nNecrosis n nApoptosis n Necrosis nDeath of the tissue (in a living organism) n nInduces inflammation and repair n nCauses include ischaemia, metabolic, trauma n Infarction = ischaemic necrosis. Ischaemia = lack of blood perfusin followed by hypoxia Morphological types of necrosis nCoagulative -In solid internal organs, with protein predominance (heart, kidneys, liver) -Caused by ischaemia (lack of blood supply) - nColliquative -in brain (generally in organs with lipid predominance), usually caused in ischaemia - nCaseous -In tuberculosis and some fungal infections n n n Morphological types of necrosis nGangrene -Necrosis with putrefaction (caused by some bacteria (clostridia) - nFat necrosis -Direct trauma of adipose tissue -Enzymatic lysis of fat dut to release of lipase (in acute pancreatitis) n coagulative necrosis – myocardial infarction IM NECROSIS - healing n→ inflammatory reaction = inflammatory infiltrate n (neutrophils, histiocytes….. lymphocytes) + afterwards nonspecific granulation tissue (fibroblasts, angiogenesis) → → maturation of the fibrous tissue → n n→ scar (within 6 weeks) + possible secondary alterations (dystrophic calcification, e.g.) n n→ pseudocyst (colliquation of a necrotic tissue) n Apoptosis nProgrammed cell death nEnergy-dependent proces for elimination/deletion of unwanted cells nBoth physiological andd pathological nInvolved in morphogenesis nReduced apoptosis in neoplasias/tumors nIncreased apoptosis results in excessive cell loss (e.g. in atrophy) nNo inflammatory response to apoptosis APOPTOSIS in physiological situations nembryogenesis (morphogenetic, histogenetic, phylogenetic) n n hormone-dependent involution n endometrial cell breakdown during the menstrual cycle n prostatic involution after castration n n defence mechanisms during immune response n death of neutrophils in an acute inflammatory response n elimination of self-reactive T-lymphocytes during their maturation in the thymus, e.g. n n elimination of damaged cells n n during aging n n n n n APOPTOSIS in pathological conditions n pathological inhibiton of apoptosis n tumors n follicular lymphoma n mammary, prostatic, e.g. , carcinomas with mutation in p53 gene) n nautoimmune diseases nSLE n n infections n herpes simplex virus n poxviruses n TBC n APOPTOSIS in pathological conditions n pathological induction of apoptosis n AIDS n n neurodegenerative diseases n m. Alzheimer, m. Parkinson, ALS n n myelodysplastic syndrome n aplastic anemia n n ischemic injury n acute myocardial infarction n n Atrophy nDecrease in size of a normally evolved organ n nReduction of cell size (simple atrophy) or cell number (numeric atrophy) or both n nMay be mediated by apoptosis n nMay be physiological (e.g. post-menopausal atrophy of uterus) n nPathological atrophy due to decreased function, loss of innervation, reduced blood or oxygen supply, nutritional impairment or hormonal insufficiency,…. ATROPHY nEtiology: n û physiologic involution (thymus) û lack of nutrition ->> cachexia û pressure atrophy (compressed tissue) û loss of function (immobilisation of a limb) û loss of blood supply û loss of innervation û loss of endocrine stimulation û hormone-induced atrophy (in the skin after topically applied corticosteroids) û idiopathic û û n Hypoplasia, aplasia nFailure of the development of an organ nFailure of morphogenesis n Thanks for your attention……..