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?

3 Doc. MUDr. Mgr. Július Hodosy, PhD., MPH.

h-index: 16

RNDr. Barbora Vlková, PhD. h-index: 8

Mgr. Veronika Borbélyová, PhD. h-index: 3

Mgr. Barbora Konečná, PhD. h-index: 2

MUDr. RNDr. Roman Gardlík, PhD. h-index: 12

RNDr. Ľubmíra Tóthová, PhD. h-index: 11

Why?

n  Biomedical research n  biology and medicine

n  Future career n  Master theses n  PhD

n  IMBM, BMC n  Bidirectional

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What?

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

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Syllabus Ø  Introduction

Ø  Syllabus, motivation, examination Ø  Cardiovascular diseases

Ø  Heart failure, hypertension, atherosclerosis, coronary artery disease, shock Ø  Respiratory diseases

Ø  Asthma, COPD, emphysema, pulmonary edema, acid base balance Ø  Gastrointestinal diseases

Ø  Ulcers, diarrhea, constipation, icterus, pancreatitis, portal hypertension, liver failure Ø  Immune disorders

Ø  immunosuppression, autoimmune diseases, allergy Ø  Hematological disorders

Ø  Anemia, leukemia Ø  Nephrology and disorders of the urinary tract

Ø  Renal failure, glomerulonephritis, urinary tract infection Ø  Cancer diseases

Ø  Carcinogenesis, Paraneoplastic syndrome, solid tumors Ø  Neuropsychiatric disorders

Ø  Stroke, multiple sclerosis, epilepsy, migraine, autism, depression, schizophrenia, neurodegeneration Ø  Metabolic & endocrine diseases

Ø  Diabetes mellitus, gout, hemochromatosis, Disorders of the thyroid, adrenal and pituitary gland, hypogonadism, hypergonadism

Ø  Gynecological diseases Ø  Preeclampsia, endometriosis, PCOS, preterm birth, amenorrhea

Ø  Musculoskeletal diseases Ø  Osteoporosis, carpal tunnel syndrome, rheumatoid arthritis, osteoarthrosis, psoriasis

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Information sources

n  Lectures n  www.imbm.sk

n  Textbooks n  Wikipedia n  Pathophysiology, internal medicine

n  Review articles n  Pubmed

n  CVTI n  www.cvtisr.sk

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Examination

n  Oral exam n  Questions according to the syllabus

n  Seminar paper n  1.12. n  One topic reviewed in detail

n  Tasks to solve n  Questions every week

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Basic terms

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

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

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

Selected symptoms & signs

n  Cyanosis n  Dyspnoe n  Icterus n  Struma n  Edema n  Palpitations n  Syncope n  Ascites

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Syndrome

n  Anemic syndrome n  Paleness n  Fatique n  Dyspnea

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Cardiovascular system I

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Circulation

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Conducting system

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Cardiac output

n  Preload n  Contractility n  Afterload

n  Frequency n  Synchronisation

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Mechanisms of heart

n  Frank-Starling mechanism

n  Inotropy – lusitropy

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Cardiovascular diseases

n  Hypertension n  Atherosclerosis n  Coronary artery disease

n  Angina pectoris n  Acute myocardial infarction

n  Heart failure n  Stroke

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Neurohumoral regulation

n  Autonomous nervous system n  RAAS system n  Endothelin n  Natriuretic peptides n  NO

Autonomous nervous system

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RAAS system

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Endothelin

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Natriuretic hormones

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NO

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Heart failure

n  Insufficient perfusion of tissues n  Normal filling

n  Forward failure n  Ejection fraction

n  Backward failure n  Edema

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Heart failure

n  Systolic n  Low ejection fraction n  Contraction failure

n  Diastolic n  Normal ejection fraction n  Filling failure

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NYHA classification n  Class I

n  No limitations of physical activity. Dyspnoe with heavy physical exertion.

n  Class II n  Some limitation of physical activity. Dyspnoe with

ordinary exertion.

n  Class III n  Definite limitation of physical activity. Dyspnoe with

minimal exertion.

n  Class IV n  Severe limitation of physical activity. Dyspnoe at rest.

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Heart failure

n  Compensation n  Catecholamines n  Frank-Starling n  Hypertrophy

n  Decompensation

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Heart failure

n  Epidemiology n  20/1000 – adult population n  150/1000 – over 75 years

n  5-year mortality 50% n  Therapy

n  ACE-inhibitors n  Beta-blockers n  Diuretics

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Symptoms of heart failure

Think FACES...

•  Fatigue

•  Activities limited

•  Chest congestion

•  Edema or ankle swelling

•  Shortness of breath

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Decompensation

Increased pulmonary venous pressure

Insterstitial edema

Alveolar edema

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Acute pulmonary edema

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Hypertrophy

n  Overload

n  Pressure n  Afterload n  Concentric hypertrophy

n  Volume n  Preload n  Excentric hypertrophy

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Valvular defects

n  Mitral/Tricuspidal n  Stenosis n  Insufficiency

n  Aortal/Pulmonary n  Stenosis n  Insufficiency

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Valvular defects

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Healthy heart

Dilation

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Healthy heart

Concentric hypertrophy

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Healthy heart

Excentric hypertrophy

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Blood pressure

n  Hypertension n  130/80 mm Hg, but... n  Many confounding factors n  Hypertrophy, encephalopathy, stroke,

hypertensive nephropathy, retinopathy... n  Primary – essential n  Secondary

n  Renal n  Renovascular n  Endocrine n  Neural, iatrogenic, gestational...

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Afterload & blood pressure

n  BP = CO x SVR n  Cardiac output n  Systemic vascular resistance

n  If CO is low, BP is maintained by ↑ SVR n  ↑ SVR = ↑ afterload

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Complications of hypertension

n  Atherosclerosis n  Stroke n  AMI n  Nephropathy n  Blindness

Cardiovascular models

n  Hypertension n  L-NAME, SHR, Dahl salt-sensitive rats

n  Atherosclerosis n  High fat diet, apoE ko mice

n  AMI n  Coronary surgery

n  Heart failure n  Isoprenalin

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Questions

n  Which genetic factors are associated with hypertension? Heritability?

n  What is the evolutionary origin of the RAAS system?

n  What is the effect of ACE inhibitors on mortality in hypertension and heart failure?

n  Which promoters are myocardium-specific? n  Why does apoE knock-out leads to

atherosclerosis?

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