Z áklad teoretickej a experimentálnej medicíny

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

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

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

4. Why? • Biomedical research • biology and medicine • Future career • Master theses • PhD • IMBM, BMC • Bidirectional 4

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

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

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

8. Examination • Oral exam • Questions according to the syllabus • Seminar paper • 1.12. • One disease reviewed in detail • Tasks to solve • Questions every week 8

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

10. 10

11. Latin I. • -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

12. Latin II. • -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

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

14. Syndrome • Anemic syndrome • Paleness • Fatique • Dyspnea 14

15. Cardiovascular system I

16. Circulation 16

17. Conducting system 17

18. Cardiac output • Preload • Contractility • Afterload • Frequency • Synchronisation 18

19. Mechanisms of heart • Frank-Starling mechanism • Inotropy – lusitropy 19

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

21. Neurohumoral regulation • Autonomous nervous system • RAAS system • Endothelin • Natriuretic peptides • NO 21

22. Autonomous nervous system 22

23. RAAS system 23

24. Endothelin 24

25. Natriuretic hormones 25

26. NO 26

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

28. Heart failure • Systolic • Low ejection fraction • Contraction failure • Diastolic • Normal ejection fraction • Filling failure 28

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

30. Heart failure • Compensation • Catecholamines • Frank-Starling • Hypertrophy • Decompensation 30

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

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

33. Decompensation Increased pulmonary venous pressure Insterstitial edema Alveolar edema 33

34. Acute pulmonary edema 34

35. Hypertrophy • Overload • Pressure • Afterload • Concentric hypertrophy • Volume • Preload • Excentric hypertrophy 35

36. Valvular defects • Mitral/Tricuspidal • Stenosis • Insufficiency • Aortal/Pulmonary • Stenosis • Insufficiency 36

37. Valvular defects 37

38. Healthy heart Dilation 38

39. Healthy heart Concentric hypertrophy 39

40. Healthy heart Excentric hypertrophy 40

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

42. 42

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

44. Complications of hypertension • Atherosclerosis • Stroke • AMI • Nephropathy • Blindness 44

45. Cardiovascular models • Hypertesion • L-NAME, SHR, Dahlsalt-sensitiverats • Atherosclerosis • Highfatdiet, apoEkomice • AMI • Coronarysurgery • Heartfailure • Isoprenalin 45

46. Questions • 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 apoE knock-out leads to atherosclerosis? 46