Zklad teoretickej a experimentlnej medicny Peter Celec stav

Základ teoretickej a experimentálnej medicíny Peter Celec Ústav molekulárnej biomedicíny, LF UK www. imbm. sk petercelec@gmail. com

Basics of theoretical and experimental medicine Peter Celec Institute of Molecular Biomedicine, LF UK www. imbm. sk petercelec@gmail. com

Who? MUDr. RNDr. Roman Gardlík, Ph. D. h-index: 12 RNDr. Barbora Vlková, Ph. D. h-index: 8 Mgr. Barbora Konečná, Ph. D. h-index: 2 Mgr. Veronika Borbélyová, Ph. D. h-index: 2 MUDr. Mgr. Július Hodosy, Ph. D. , MPH. h-index: 14 3

Why? n Biomedical research n n Future career n n n biology and medicine Master theses Ph. D IMBM, BMC n Bidirectional 4

What? n n n Principles of common diseases Etiology Pathogenesis Symptoms & signs Treatment approaches Models 5

Syllabus Ø Introduction Ø Ø Cardiovascular diseases Ø Ø Diabetes mellitus, gout, hemochromatosis Endocrine diseases Ø Ø Stroke, multiple sclerosis, epilepsy, migraine, autism, depression, schizophrenia, neurodegeneration Metabolic diseases Ø Ø Carcinogenesis, Paraneoplastic syndrome, Neuropsychiatric disorders Ø Ø Anemia, inflammation, immunosuppression, autoimmune diseases, allergy, leukemia, lymphoma Cancer diseases Ø Ø Renal failure, glomerulonephritis, preeclampsia, urinary tract infection, amenorrhea Blood and immune disorders Ø Ø Ulcers, diarrhea, constipation, icterus, pancreatitis, portal hypertension, liver failure Nephrology and disorders of the genitourinary tract Ø Ø Asthma, COPD, emphysema, pulmonary edema, acid base balance Gastrointestinal diseases Ø Ø Heart failure, hypertension, atherosclerosis, coronary artery disease, shock Respiratory diseases Ø Ø Syllabus, motivation, examination Disorders of the thyroid, adrenal and pituitary gland, hypogonadism, hypergonadism Musculoskeletal diseases Ø Osteoporosis, carpal tunnel syndrome, rheumatoid arthritis, osteoarthrosis, psoriasis 6

Information sources n Lectures n n Textbooks n n n Wikipedia Pathophysiology, internal medicine Review articles n n www. imbm. sk Pubmed CVTI n www. cvtisr. sk 7

Examination n Oral exam n n Seminar paper n n n Questions according to the syllabus 1. 12. One disease reviewed in detail Tasks to solve n Questions every week 8

Basic terms n n n n Physiology vs. Pathophysiology Pathology vs. Pathophysiology Etiology vs Pathogenesis Symptoms vs Signs Syndrome Health vs Disease Latin terms 9

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Latin I. n n n n n -brady – bradypnoe, bradykardia -tachy – tachypnoe, tachykardia -hypo – hypopnoe, hypoglycemia -hyper – hyperpnoe, hyperglycemia -poly – polydipsia, polyphagia -oligo – oliguria, oligofrénia -a/an – apnoe, anuria -pseudo – pseudocyst -endo – endoscopy -ekto – ectopic 11

Latin II. n n n n n -osis – degeneration - arthrosis -itis – inflammation - hepatitis -oma – tumor - myoma -algia – pain - artralgia -stenosis – narrowing - pylorostenosis -pathia – disease - hepatopatia -lithiasis – stone - nephrolithiasis -rrhagia – bleeding - metrorrhagia -emia – blood - glycemia, natriemia, kaliemia -uria – urine - glykosuria, natriuria 12

Selected symptoms & signs n n n n Cyanosis Dyspnoe Icterus Struma Edema Palpitations Syncope Ascites 13

Syndrome n Anemic syndrome n n n Paleness Fatique Dyspnea 14

Cardiovascular system I

Circulation 16

Conducting system 17

Cardiac output n n n Preload Contractility Afterload Frequency Synchronisation 18

Mechanisms of heart n Frank-Starling mechanism n Inotropy – lusitropy 19

Cardiovascular diseases n n n Hypertension Atherosclerosis Coronary artery disease n n Angina pectoris Acute myocardial infarction Heart failure Stroke 20

Neurohumoral regulation n n Autonomous nervous system RAAS system Endothelin Natriuretic peptides NO 21

Autonomous nervous system 22

RAAS system 23

Endothelin 24

Natriuretic hormones 25

NO 26

Heart failure n Insufficient perfusion of tissues Normal filling n Forward failure n n n Ejection fraction Backward failure n Edema 27

Heart failure n Systolic n n n Low ejection fraction Contraction failure Diastolic n n Normal ejection fraction Filling failure 28

NYHA classification n Class II n n Some limitation of physical activity. Dyspnoe with ordinary exertion. Class III n n No limitations of physical activity. Dyspnoe with heavy physical exertion. Definite limitation of physical activity. Dyspnoe with minimal exertion. Class IV n Severe limitation of physical activity. Dyspnoe at rest. 29

Heart failure n Compensation n n Catecholamines Frank-Starling Hypertrophy Decompensation 30

Heart failure n Epidemiology n n 20/1000 – adult population 150/1000 – over 75 years 5 -year mortality 50% Therapy n n n ACE-inhibitors Beta-blockers Diuretics 31

Symptoms of heart failure Think FACES. . . • • • Fatigue Activities limited Chest congestion Edema or ankle swelling Shortness of breath 32

Decompensation Increased pulmonary venous pressure Insterstitial edema Alveolar edema 33

Acute pulmonary edema 34

Hypertrophy n Overload n Pressure n n n Afterload Concentric hypertrophy Volume n n Preload Excentric hypertrophy 35

Valvular defects n Mitral/Tricuspidal n n n Stenosis Insufficiency Aortal/Pulmonary n n Stenosis Insufficiency 36

Valvular defects 37

Healthy heart Dilation 38

Healthy heart Concentric hypertrophy 39

Healthy heart Excentric hypertrophy 40

Blood pressure n n n Hypertension 140/90 mm Hg, but. . . Many confounding factors Hypertrophy, encephalopathy, stroke, hypertensive nephropathy, retinopathy. . . Primary – essential Secondary n n Renal Renovascular Endocrine Neural, iatrogenic, gestational. . . 41

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Afterload & blood pressure n BP = CO x SVR n n n Cardiac output Systemic vascular resistance If CO is low, BP is maintained by SVR n SVR = afterload 43

Complications of hypertension n n Atherosclerosis Stroke AMI Nephropathy Blindness 44

Cardiovascular models n Hypertesion n n Atherosclerosis n n High fat diet, apo. E ko mice AMI n n L-NAME, SHR, Dahl salt-sensitive rats Coronary surgery Heart failure n Isoprenalin 45

Questions n n n Which genetic factors are associated with hypertension? Heritability? What is the evolutionary origin of the RAAS system? What is the effect of ACE inhibitors on mortality in hypertension and heart failure? Which promoters are myocardium-specific? Why does apo. E knock-out leads to atherosclerosis? 46