WEEK 1：Overview of the cardiovascular systemLearning Objective• explain the basic anatomy of the heart and its arrangement into 4 chambers.• describe the location and function of the heart valves.• list in sequence the direction of blood flow through the four chambers of the heart.• appreciate that blood flows in series through the systemic and pulmonary circulations.• explain what causes fluid to flow through a tube.• understand the relationship between blood flow, pressure and resistance• appreci ate the three factors that influence the resistance to flow through a tube.Why do we have a circulatory system?distribute nutrients/hormones O2remove wastes + CO2thermo regulationtransport antibodies and white blood cellspenile erectionHeart (pump)Aortic and Pulmonary Valves∙(semilunar valves)Allow flow from ventricles into arteries (aorta or pulmonary artery)∙but prevent backflow from arteries to ventriclesAtrioventricular Valves∙mitral (bicuspid) valve (between left atrium and ventricle)∙tricuspid valve (between right atrium and ventricle)Allow flow from atria into ventricles∙but prevent flow from ventricles back into atriaDifference in pressure causes flowFlow is always from region of high pressure toregion of lower pressureIt is the DIFFERENCE in pressure that is important,not the absolute pressure.Flow is proportional to the pressure difference(F P)Directly proportional if flow is laminar.What is the main anatomical difference between the femoral artery andthe popliteal artery?Which artery has the higher peripheral resistance (PR)?What do you think is the relationship between artery lengthandperipheral resistance (to blood flow)?Changing the radius alters the resistance to flowFlow through a vessel increases in proportion to the fourth power of the radius of the vessel (Poiseuille’s law).Viscosity = blood is thicker than water% volume of blood occupied by red blood cellsHaematocrit = 45% in men= 42% in womenMen have a slightly higher oxygen carrying capacity of their blood (more haemoglobin)Athletes sometimes artificially elevate their haematocrit (e.g. with synthetic erythropoietin/EPO or via blood doping). What effect will this have on viscosity and blood flow in arterioles supplying the leg?Why are athletes so tempted by ‘blood doping’?Blood viscosity is largely determined by haematocrit:Haematocrit is usually maintained relatively constant:- can be abnormally low in anaemia- abnormally high with severe dehydration or synthetic erythropoietin (EPO/blood doping)3 factors determine resistance to flow:∙the length of the tube:∙the radius of the tube:∙the viscosity of the fluid:BASIC FLOW EQUATION: F = delta PRQ1 Under control conditions, flow through a blood vessel is 100 ml/min under apressure gradient of 50 mm Hg. What would be the approximate flow through thevessel after increasing the vessel radius to four times normal, assuming the pressuregradient was maintained at 50 mm Hg?(a) 300 ml/min(b) 1600 ml/min(c) 1000 ml/min(d) 16,000 ml/min(e) 25,600 ml/minQ2 Which blood vessel has the highest vascular resistance (A, B, C, D or E)?Blood flow (ml/min) Pressure gradient (mmA 1000 100C 1400 20D 1600 80E 1800 40Q3 Blood flows in continuous loop through the systemic & pulmonary circulations (blood flow equal) MAP pulmonary ~15 mmHgMAP systemic ~95 mmHgWhy the same flow but different driving pr essures?WEEK 2 & 3 Excitation of the heartREFERENCES:Vander (Human Physiology, 13th edition) = see page references throughout lecture notesPracs/simulation = Practical 2: Human Cardiovascular Function’; simulations(MOODLE) = Heart conduction.Learning objective• descri be the conducting system of the heart and how electrical activity spreads from the sino-atrial node to the rest of the heart.• describe the main ionic movements during a ventricular action potential.• explain how sino-atrial node pacemaker cells spontaneously generate action potentials.• describe the 3 phases of the ECG, including how they relate to excitation of the heart and the cardiac action potentials • describe some common cardiac arrhythmias• explain why the sino-atrial node acts as the normal pacemaker of the heart.• explain how sino-atrial node pacemaking (i.e. heart rate) is regulated by the autonomic nervous system.Heart rate ↑ during exercise∙HR ↑ in linear fashion to increase O2 delivery to active muscle.∙Exercise training ↓ resting HR. Trained athletes: resting HR as low as 40 beats/min.∙Maximum HR not altered (↓ with age).∙Return of HR to normal post exercise is indicative of aerobic fitnessExcitation (action potential) is essential for cardiac contraction:Electrical conduction: cardiac myocytes connected via gap junctionsExcitation of the heart:Excitation originates in the sinoatrial node→internodal pathways in the atria→atrioventricular node(slowed conduction ~0.05 m/s)→Bundle of His (two branches)→Purkinje fibres (rapid conduction ~3 - 5 m/s)Slow conduction through the atrio-ventricular node, WHY?Cardiac action potentials cause the excitation of the heart:Voltage difference across the cell membrane =membrane potentialVentricular action potential= stable resting membranepotential, plateau phasePacemaker action potential = no stable resting potential(pacemaker potential), less negative maximum diastolicpotential (MDP)Ionic mechanisms underlying the ventricular action potentialVentricular resting membrane potential:EXTRACELLULAR FLUID INTRACELLULAR FLUID[Na+]e 145 mM [Na+]i 15 mM[Ca2+]e 2 mM [Ca2+]i 0.0001 mM[K+]e 5 mM [K+]i 150 mMVentricular action potential (depolarization)Depolarization= opens ‘fast’ voltage-sensitive Na+ channelsDepolarization & plateau= ‘slow’ voltage-sensitive Ca2+ channelsRepolarization = voltage-sensitive K+ channelsIonic mechanisms underlying the spontaneous sino-atrial node (pacemaker) action potential:The puffer fish contains tetrodotoxin (TTX) = selective inhibitor of fast Na+ channelsTTX does nothing to cardiac pacemaker action potentials!What is the pacemaker (or funny) current?Called the ‘f’ for funny or ‘h’ for hyperpolarization current.Inward flux of Na+.The slope of the pacemaker potential determines heart rate.Sino-atrial node (pacemaker) action potential:- Inward Na+ and Ca2+- Gradual decrease in outward K+The electrocardiogram (ECG):∙ A record of the heart’s electrical activity, recorded from the surface of the body.∙As excitation sweeps over the heart at any instant some parts of the heart will be positively charged while other parts are negatively charged.∙This causes currents to flow in the medium surrounding the heart.∙Because the body is a very good conductor these small currents can be detected at the body surface.∙The ECG is a recording of these small currents and reflects the depolarisation and repolarisation of different regions ofthe heart.The ECG used as clinical diagnostic tool:Used by cardiologists to determine:(1) the anatomical orientation of the heart and the relative sizes of its chambers(2) disturbances in cardiac rhythm and conduction(3) the extent and location of ischaemic damage to the myocardium(4) the effects of drugs or abnormal concentrations of various plasma electrolytes on the hear。