Cardiovascular System & Its Diseases Lecture #1

Cardiovascular System & Its DiseasesLecture #1Cardiovascular SystemDr. Derek Bowie,Department of Pharmacology & Therapeutics,Room 1317, McIntyre Bldg, McGill Universityderek.bowie@mcgill.ca

?Why do we bother teachingCardiovascular Pharmacology?

***** Related Disorders

Mainly Thro’ Our Own HabitsSocio-Economic Status Too!

Overview of Lecture SeriesBits ‘N’ Pieces1. Cardiovascular SystemBlood, Heart, Blood-VesselsKeeping It Under ControlHeart Rate, Blood PressureWhen Things Go WrongHypertension, Ischemia, Heart Failure, ArrhythmiasAetiology2. HypertensionDiagnosisTreatmentSympathoplegic Drugs, Diuretics, Vasodilators, Angiotensin AntagonistsAetiology3. Myocardial IschemiaDiagnosisTreatmentSymptomatic: Nitrites, Calcium Channel Blockers, β-BlockersProphylactic: Lipid lowering, Anti-coagulant, Anti-platelet drugsAetiology4. Heart Failure &Cardiac ArrhythmiasDiagnosisTreatmentHeart Failure: Nitrites, Calcium Channel Blockers, Diuretics,Angiotensin Antagonists, β-Blockers, β-Receptor Agonist, Cardiac GlycosidesArrhythmias: Channel Blockers (Groups I – IV), Miscellaneous

What To Read?Chapters 8 -19Chapters 2 - 3

What Will YouLearn Today?Don’t Put the Cart Before The HorsePhysiology Then Pharmacology1. Components of the CV System: Blood, Heart & Blood Vessels2. Regulation: Heart Rate, Blood Pressure (Autonomic NS) & Pharmacology3. Playing Doctor: Mystery Case !!!!!!!!!!!!!!!!

1. Components of the CV SystemSimple SystemOpen Circulatory System(single-celled organisms use their surface for nutrientand gaseous exchange)(common to molluscs and arthropods; blood bathes tissueswith flow being sluggish)There are different types of Circulatory Systems

1. Components of the CV SystemClosed Circulatory SystemVertebrate Cardiovascular System(in echinoderms and vertebrates; blood enclosed inspecialized vessels)(multi-chambered heart with complex valves; bloodtransported in vessels)

A Little Bit of HistoryFish:Single (2-chambers) circulatory system (gills to rest of body)Amphibians / Reptiles:Double (sometimes 3-chambers though)Birds / Mammals:Complete separation (4-chambers)4th Century BC:Herophilus distinguished arteries from veins (blood collectsin veins at death and empties from arteries; therefore,postulated arteries carried air)2nd Century AD:Galen assigned different functions to veins and arteries1242:Ibn Nafis first to describe blood circulation in body1628:William Harvey described circulatory system in influentialbook but failed to identify the capillaries

Heart Rate During Embryonic DevelopmentHeart is one of the first organs to appear during development

(i) Blood

Components Of BloodSome antihypertensives regulate blood volume

Cellular Components Of BloodRed blood cellsLeucocytesPlateletAnticoagulants are used to prevent further blood vessel occlusionMagnification x10,000

Dynamic Nature Of RBCsBlood ClottingSickle Cell anaemiaMagnification x 5,000

(ii) Heart

Cardiac CyclePwaveAtrial DepolarizationQRScomplex Ventricular depolarizationTwaveVentricular RepolarizationNB Atrial repolarization is masked by QRScomplex* In hypertension arterialpressure is elevated whichcompromises the ability of theventricles to pump effectively *AV valveclosureSemilunar valveclosure

(Semi-lunar valves)Determining Normal Heart BehaviorAdult HeartLinkFoetal HeartLinkNormal functioning heart consists of pairs of sounds. Each pair, lubdub, lub-dub begins with the 1st sound and ends with the 2nd. Themajor audible components are related to mitral, tricuspid and semilunar valve closure.(tricuspid)(bicuspid)Early Systolic MurmurEarly systolic murmurs begin withthe first sound and peak in the firstthird of systole. Early murmorshave the greatest intensity in theearly part of the cycle. Commoncauses are a small ventricularseptal defect (VSD), or theinnocent murmurs of childhood.This recording is an early systolicmurmur from a 20 year-old femalewith a small muscular VSD.LinkMidSystolic MurmurContinuous MurmurA midsystolic murmur beginsshortly after the first sound, peaks inthe middle of systole, and does notquite extend to the second sound. Itis also known as ejection murmur.The most characteristic feature ofthis murmur is its cessation beforethe second sound, thus leaving thislatter sound identifiable as a discreteentity. This type of murmur iscommonlyheardinnormalindividuals, particularly in the youngwho usually have increased bloodA pan diastolic murmur beginswith the second sound andextends throughout the diastolicperiod. Patent ductus arteriosus(PDA) is a classical example ofthis murmur. This condition isusually corrected in childhood. It isheard best at base left and hasboth a systolic and diastoliccomponent. It is known as acontinuous murmur.Linkvolumes flowing over normal valves.LinkCourtesy of: Virtual Stethoscope Web Sitehttp://sprojects.mmi.mcgill.ca/mvs/mvsteth.htm

(iii) Blood Vessels

Circulatory Routes

One-Way Valve In A Vein

Skeletal Muscle Aids Returning Blood To The Heart

Hemodynamic Properties Of Blood Vessels

Contractility is regulatedby drugs

Atherosclerosis Restricts Blood Flow In VesselsCan lead to claudication(leg pain due to poor circulation)

Regulating Heart Rate2 Things To Remember:Cardiac Pacemaker Activity & the Autonomic NS

What Is The Autonomic Nervous System?Autonomic NS(Involuntary)Somatic NS(Voluntary)

Sympathetic & Parasympathetic NS HaveOpposing Actions On The Heart

Typical Cholinergic & Noradrenergic Nerve Endings

Homeostatic Regulation Of Heart RateMarey’s Law: Inverse relationship between blood pressure & heart rate

Autonomic Nervous System Regulates Heart RateContainBaroreceptorsMedulla provides autonomicregulation of heart rateInnervation that contributesto the Carotid Sinus & Aortic Reflex

Regulating Blood Pressure

Controlling Blood Pressure At Multiple Regulatory Sites

Autonomic & Hormonal Control Of Cardiovascular FunctionAutonomic Loop is fast (seconds to minutes) whereasthe hormonal loop is slower (hours to days)

NAME MY DISEASE

Cardiovascular System & Its Diseases:Autonomic Nervous SystemCase StudyThe patient is 21 yrs old and has experienced frequent episodes ofblurred vision, dizziness, faintness and syncope for as long as she canremember.She is the only child; her mother has a history of two spontaneousabortions at 12 and 14 weeks of gestation and one stillborn child at 38weeks. The subject had a normal development during childhood;although she was considered apathetic and she avoided physicalexercise.Is this a disorder of the Sympathetic NS,Parasympathetic NS or Both?

Cardiovascular System & Its Diseases:Autonomic Nervous SystemCase StudyPlasma noradrenaline and adrenaline were undetectable but dopaminewas 7 times normal. Upon 60o head-up tilting, noradrenaline andadrenaline did not change (in normal subjects, they increase) butdopamine increased (usually it does not).What’s wrong with this patient?

Cardiovascular System & Its Diseases:Autonomic Nervous SystemCase StudyThis patient has a congenital deficiencyin dopamine β-hydroxylase;The enzyme which converts dopamineto noradrenaline.

What’s Next?

Disease StatesLecture #2.Hypertension most common, asymptomaticLecture #3.Myocardial Ischemia demand-supply imbalanceLecture #4.Heart Failure multifactorial Arrhythmias impulse abnormality

Cardiovascular System And Its DiseasesWhat Have We Learned?1. Components: Blood, Heart & Blood Vessels2. Regulation: Heart Rate & Blood Pressure3. Diseases: Hypertension, Angina, Heart Failure & Arrhythmias

Further Reading?Pages 56 - 64, 99 -115, 121-129Chapters 11 - 15

Cardiovascular System & Its Diseases: Autonomic Nervous System The patient is 21 yrs old and has experienced frequent episodes of blurred vision, dizziness, faintness and syncope for as long as she can