General Etiology. Concepts of disease and pathological state. Etiology and pathogenesis. Intrinsic and extrinsic causes of disease.
Genetic and Molecular Pathology. Classification of the nuclear genome diseases: chromosomal, monogenic and complex traits (polygenic multifactorial). Imprinting, uniparental disomy and epigenetic effects. Mosaicism. Mitochondrial genome diseases. Molecular mechanisms responsible for the reduced biosynthesis and/or increased protein degradation. Alpha and beta thalassemia: genetic and phenotypic heterogeneity, genotype-phenotype correlations in thalassemia. Qualitative alterations in protein biosynthesis. Sickle-cell anaemia model and Hb Zurich. G6PD deficiency. Atherosclerosis as a model of a complex trait disease: pathogenesis, risk factors and prevention. Obesity: etiological classification and related diseases. Role of drugs in the etiology of obesity. Pathophysiology of obesity and of its complications. Systemic arterial hypertension: etiological classification and complications. Risk factors and pathophysiological mechanisms of hypertension. Pathophysiology of the lipoprotein metabolism. Molecular pathology of the LDL receptor, APO-B100, ARH and PCSK9. Monogenic and polygenic familial hypercholesterolemia. Diabetes: etiological classification and complications. Role of drugs in the etiology of diabetes. Pathophysiology of common polygenic and multifactorial forms of diabetes. Downregulation of insulin receptors and selective post-receptor insulin resistance. Monogenic forms of diabetes. Clinical classification of insulin resistance due to insulin receptor defects. Classification of receptor defects, codominance, dominant negative alleles and genotype-phenotype correlations in insulin resistance. Pathophysiology of metabolic syndrome. Examples of altered sensitivity to drugs. Introduction to gene therapy.
Diseases due to physical and chemical agents. Radiations, acute whole-body irradiation, electricity, magnetism. Heat: malignant hyperthermia, heatstroke, sunstroke, drug-induced hyperthermia, burns. Cold exposure and freezing. Diseases due to chemical causes.
Diseases due to biological agents. Parasites. Virulence and resistance factors. Diseases due to endotoxins and exotoxins. Infections due to pyogenic bacteria. Sporogenic bacteria. Salmonellae and pathogenesis of typhoid fever. Diseases due to Helicobacter pylori. Tuberculosis. Syphilis. Viruses, structural and genomic organization. Ways of infection. Smallpox. Varicella-zoster virus. Infectious mononucleosis. HSV I and HSVII. Poliomyelitis. Viral hepatitis, acute and chronic (cirrhosis and neoplastic evolution). HIV. Prion diseases: molecular mechanisms and examples of sporadic, familial, infectious and iatrogenic forms.
Inflammation. Causes of inflammation. Plasma- and tissue-derived mediators of inflammation. Cells in acute and chronic inflammation. Chemotaxis and phagocytosis. Differences between acute and chronic inflammations. Granulomatous and interstitial chronic inflammation. Outcome of inflammatory processes. Restoration processes and granulation tissue.
Pathophysiology of thermoregulation and fever. Thermoregulation. General response of host to heat and cold. Causes of fever. Pathological modifications of the body temperature. Hypothermia and hyperthermia. Morphology of the thermal curve.
Immunology. Antigens and antibodies. Organs and cells of the immune system. Subclasses of T- and B-lymphocytes. Major histocompatibility complex (MHC). The complement system. The immune response. The main antigen-antibody reactions. Immediate and delayed hypersensitivity diseases. Drug hypersensitivity: cross-reactions. Classifications of immunodeficiency disorders. AIDS and adenosine deaminase deficiency. Classification of autoimmune diseases. Infectious agents in autoimmune diseases.
Oncology. Hyperplasia, hypertrophy, metaplasia, dysplasia, anaplasia, neoplasia. Benign and malignant tumors. Histological classification and main morphological features of human benign and malignant tumors. Acute and chronic myeloid leukemia. Acute and chronic lymphoid leukemia. Lymphoma. Plasmacytoma. In situ carcinoma. Mechanisms and ways of metastasization. Chemical carcinogenesis. UV radiation carcinogenesis. Ionizing radiation carcinogenesis. Steps of carcinogenesis. Tumor initiation, promotion and progression. Initiating and promoting compounds, including drugs. Biological agents and cancer: role of bacteria, viruses, parasites and fungi. Viral carcinogenesis. Tumorigenic DNA and RNA viruses. Acute and chronic transforming viruses. Viral oncogenesis. Oncogenes, tumor suppressors and genes responsible for the maintenance of genome integrity and for DNA repair. Genetics of the familial and hereditary neoplasia: HNPCC, Xeroderma pigmentosum, ATM, BRCA, APC, MUTYH, retinoblastoma, Li-Fraumeni syndrome. Immunity and cancer: tumor escape and immune checkpoints.
Pathophysiology of blood, heme, hemostasis and shock. Pathophysiology of erythropoiesis. Blood count and white blood cell composition. Anemia: general features, classification, hereditary and acquired causes. Jaundice: etiological classification and pathophysiology. Hemostasis: etiological classification and pathophysiology. Definition and etiological classification of shock. Pathophysiology of shock.
