Cardiovascular

Cardiovascular - CONTACT INFO Michael Guevara Physiology...

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Unformatted text preview: CONTACT INFO Michael Guevara Physiology Department McGill University McIntyre Medical Sciences Building Room 1018 398-4320 michael.guevara@mcgill.ca CARDIOVASCULAR PHYSIOLOGY CARDIOVASCULAR PHYSIOLOGY COURSE RESOURCES 1. MEDIA SITE LIVE VIDEO (PowerPoint, voice) AUDIO (.wma, .mp3) 2. TUTORS 3. TUTORIAL EXAM EXAM 1. Textbook ─ Chapter 12: sections A-E (pgs. 387-459) not section F (pg. 458-474) 2. Lectures 3. Lecture Slides “memorization questions” “thinking questions” CVS FUNCTION FUNCTIONS OF THE CARDIOVASCULAR SYSTEM •bringing O2 to cells from lungs •bringing fuel to cells (e.g., glucose from liver to brain) •bringing nutrients into body (e.g., from intestine to liver, fat) •removal of waste products (e.g., CO2 to lungs; by respiratory system ammonia to liver → urea → kidneys by excretory system •circulation of hormones (e.g., adrenaline from adrenal glands to skeletal muscles) •circulation of immune cells and antibodies •regulation of electrolytes – Na+, K+, Cl−, …(e.g., exercise) •regulation of pH (lungs, kidney) pH=7.4 in the blood and 7.0 in the cytosol •H20 balance, osmoregulation (e.g., exercise: over-hydration) •thermoregulation (e.g., exercise, hypothermia) • … - interaction with the external environment - transport, move stuff around AMOEBA WHO DOESN’T NEED A CARDIOVASCULAR SYSTEM? - about 0.25mm - transport of O2 and CO2 - diffusion - O2 will combine with C to form CO2 - pseudopod phagocytic cell - diffusion does not produce a large enough flux/flow in multicellular organisms, the distance is too large http://www.lima.ohio-state.edu/academics/biology/images/amoeba.jpg DIFFUSION: The spontaneous movement of particles caused by random thermal motion LUNG TO HEART TO LUNG red blood cell capillary diffusion - red blood cell is circulated by cardiovascular system by bulk flow=convection - diffusion governs the movement of gases from the circulation into the red blood cells O2 5 μm CO2 convective or bulk flow convective or bulk flow 10 μm http://www.academy.de/linksection/cva/01_cva/03_coronary_heart_disease/sites/index03_03_01b.html DIFFUSION DIFFUSION – FICK’s LAW - flux is proportional to concentration gradient - the concentration gradient is spatial, how the concentration is changing in space - the larger the concentration gradient, the larger the flux flux = flow = D × concentration gradient unit area ⎛ C - Cin ⎞ = D × ⎜ out ⎟, d ⎝ ⎠ D = diffusion constant DCO2 DO2 If the concentration of oxygen and carbon were made the same outside and inside the membrane, CO2 will diffuse 20 times faster than oxygen A = 20 flow = flux × area = D A (Cout - Cin ) d d - the area of the alveolus is 100 square meters - flux is unchanged by large area - flow is increased with large surface area if area increases, the flow across that area will increase - but the flux will remain the same, it is expressed per unit area HEART, VESSELS, BLOOD CARDIO-VASCULAR SYSTEM pump: HEART pipes: VESSELS fluid: BLOOD greek latin kardia: heart vas: vessel INSECT THE INSECT HEART opens at the brain - three hearts - blood (hemolymph) gets pumped along a vessel to the brain - the vessel ends - the blood percolates through the rest of the organism, bathing the rest of the organs - the hemolympth gets sucked back in through holes and pumped again to the brain - blood is not always contained in the cardiovascular system, a considerable amount is outside open circulation small openings in chambers of heart http://www.ladybuglady.com/circulation.htm FISH PISCINE CIRCULATION - blood is pumped from the heart to the gills, where oxygen and carbon dioxide exchange takes place (by diffusion) due to the partial pressure gradient - blood from gills is pumped directly to the rest of the body - closed circulatory system, blood does not leave the cardiovascular system - single loop system - heart has 2 chambers closed circulation single-loop circulation 2 chambers http://www.biologycorner.com/bio2/notes34-amph.html AMPHIBIAN & MOST REPTILES AMPHIBIAN & REPTILIAN CIRCULATIONS - three chambered heart: right atrium, left atrium, single ventricle - closed circulation - two loops: pulmonary and systemic circulation - ventricle pumps blood into both chambers - there is a built in inefficiency - some deoxygenated blood will be pumped into the systemic circulation - the blood in the ventricle is mixed - frog can also perform gas exchange at the skin closed circulation double-loop circulation 3 chambers http://www.biologycorner.com/bio2/notes34-amph.html Fig. 12.02 AVIAN AND MAMMALIAN CIRCULATIONS (two hearts: right and left) RIGHT HEART: PULMONARY or PULMONIC CIRCULATION - closed circulation, two loops, four chambered heart - a septum has formed, separating the left and right sides of the heart - fully oxygenated blood is received by the left atrium, pumped to the left ventricle and then to the rest of the body - separation between oxygenated and deoxygenated blood - two separate circulations: pulmonary and systemic LEFT HEART: SYSTEMIC CIRCULATION closed circulation double-loop circulation 4 chambers SERIES-PARALLEL SERIES-PARALLEL SYSTEM - a given volume is flowing through the circulation at any point in time - 5L/min - cardiac output, the flow of blood ejected by the heart per minute - the only way to unbalance flow is to lose or gain volume of blood - flow of blood from the left and right heart remain the same because under normal conditions you are not losing or gaining any blood - skeletal muscle receives most flow (25-30%) - it is the largest organ in your body - about half your body weight is muscle 5 mm Hg 100 mm Hg Fig. 12.44 WHERE IS THE BLOOD? - 60% percent of the blood is in the venous system - 10% in the ateries - 10% in heart - 10% in arterioles - 10% in lungs - veins - capacitance vessels - arteries - resistance vessels - blood in veins is largely a reservoir, can be mobilized upon hemorrhage arterial system: resistance venous system: capacitance PRESSURE, FLOW, RESISTANCE FLOW - flow is caused by a pressure difference PRESSURE RESISTANCE size of vessel, viscosity of blood resistance to flow FLOW FLOW - change in volume per unit time - cardiac flow can not always be calculated by measuring the absolute change in volume - must be normalized per 100g of tissue ΔV Flow = Δt volume/time mL/min; L/min cardiac output = 5 L min-1 normalized: mL/min/100 gm ΔV FLOW VELOCITY CROSS SECTIONAL AREA and FLOW VELOCITY flow = area × velocity Units? cm3/sec = cm2 × cm/sec complication: velocity not the same everywhere flow = area × mean velocity Fig. 12.39b CROSS SECTIONAL AREA and FLOW VELOCITY flow = area × mean velocity the average velocity of blood must decrease when blood enters the capillaries (which have a much larger cross sectional area) in order to maintain constant flow PRESSURE PRESSURE Force Pressure = Area S.I. Unit: pascal (Pa) = newton m2 Practical unit: cm H20 ; mm Hg usually what venous pressure is measured in blood pressure = 120/80 mm Hg central venous pressure = 6 cm H20 HYDROSTATIC PRESSURE HYDROSTATIC PRESSURE A h both rho and g are fairly constant define pressure only in terms of h V = volume = area × height = Ah M = mass = density × volume = ρ V = ρ Ah (ρ = " rho ") the density of blood is relatively unchanged and it is very similar to water F = force = mass × acceleration due to gravity = mg = ρ Ahg P = pressure = force per unit area = F/A = ρ gh 1 mm Hg = 14 mm H2O = 1.4 cm H2O Hg is about 15x as dense as water ATMOSPHERIC PRESSURE pressure flow is driven by a pressure difference between two points P = ??? zero = atmospheric pressure = 14.7 lbs/sq. in. = 1 kg cm-2 = 760 mm Hg = the pressure exerted by a column of air extended upwards towards the end of the atmosphere h (cm) define Patm to be zero in cardiovascular physiology P = h cm H2O NON-HYDROSTATIC PRESSURE NON-HYDROSTATIC PRESSURE P=? saline before squeezing the bag, the pressure a the end will be zero Pinlet apply force/ pressure to the bag - flow results - fluid flows from areas of high pressure to areas of low pressure - moving towards the bag, pressure will decrease Poutlet = ? STEPHEN HALES STEPHEN HALES (1733) - took horses that were about to be slaughtered and worked on them - glass tube was inserted into the carotid artery - blood leaves the artery and into the tube - the blood will rise in the tube until it stops - at that point the blood pressure will be in equilibrium with gravity - hydrostatic pressure downward - arterial pressure upward - can measure the arterial pressure of the horse by measuring the hydrostatic pressure - measure the height of the column - 280cm BP = ??? 280 cm H2O = 20 cm Hg = 200 mm Hg CVP LINE CENTRAL VENOUS PRESSURE manometer - CVP - pressure in the central veins - insert a catheter connected to a saline bag into the brachial vein, and feed it through the venous network into the right atrium - when the switch is flicked, the catheter is connected to the manometer and not the saline fluid anymore - measure the height of fluid in the monometer - venous pressure will be a few cm of water saline 0 catheter CVP – JUGULAR VEINS CENTRAL VENOUS PRESSURE looking at the height of the vein can identify increased central venous pressure, can be caused by increased right atrial pressure - vein is distended http://medicine.ucsd.edu/clinicalmed/heart.htm CVP ≈ 5-10 cm H20 JUGULAR VEIN DISTENSION JUGULAR VEIN DISTENSION - the height of the jugular vein is much larger, it is distended - the pressure inside the vein is higher, stretches the vein - can be caused by increased pressure in the right atrium Györik & Menafoglio, 2006 hours after draining the fluid - one of the lungs is collapsed - the chest is filled with pus so that one lung is pushed over to the side and the other is collapsed - the heart is squeezed cause increased right atrial pressure PERFUSION PRESSURE VESSEL PERFUSION PRESSURE Pin Pout perfusion pressure = inlet pressure – outlet pressure ΔP = Pin – Pout - the pressure that perfuses the vessel, allows blood to flow through the vessel PERFUSION PRESSURE ORGAN PERFUSION PRESSURE Pa ORGAN Pv perfusion pressure = arterial pressure – venous pressure what drives flow through the organ - mainly the arterial pressure ΔP = Pa − Pv = ~Pa , since normally Pa >> Pv - perfusion pressure can reasonably approximated by the arterial pressure - this is not the case in disease where the arterial pressure or venous pressures can be abnormal NO FLOW NO PERFUSION PRESSURE → NO FLOW Pin Pout - the inlet and outlet pressures are equal - there is no flow, perfusion pressure is zero Pin = Pout ⇒ ΔP = 0 ⇒ flow = 0 Fig. 12.04 – first P1 P2 flow = 10 ml/min Fig. 12.04 - second P1 P2 flow = ??? ml/min - even if the inlet and outlet pressure change, flow will remain the same, absolute pressure do not matter, on the difference of pressure between the inlet and outlet - flow is dependent on perfusion pressure - for a given perfusion pressure, decreasing the diameter of the vessel will increase flow Perfusion Pressure Flow = Resistance RESISTANCE RESISTANCE Resistance = Perfusion Pressure Flow Resistance = Perfusion Pressure Flow = 90 mm Hg = 9 mm Hg ml-1 min 10 ml min-1 = 540 mm Hg ml-1 sec = 540 PRU (peripheral resistance unit) LAMINAR FLOW LAMINAR FLOW - you can calculate the resistance of an organ or part of the because the flow through most areas of the cardiovascular system is laminar or smooth - there are only a few areas where the flow of blood is not smooth, but rather pools, or forms eddies parabolic velocity profile parabolic flow = smooth flow, laminar flow streamline flow POISSEUILLE’S LAW POISSEUILLE’S LAW if flow is laminar, you can calculate the resistance of a vessel L A 8πν L 8πν L 8ν L R= = = 2 2 )2 π r 4 A (π r ν = viscosity of the fluid (ν = “nu”) R ∝ 1/r4 CONTROL OF VESSEL RESISTANCE - a small change in radius of a vessel will have a large effect on resistance - flow of blood is largely controlled by resistance and the resistance of the vessels is mostly controlled by the radius local metabolites innervation hormones - there are local controls of blood vessel constriction/dilation (chemical, muscular, nervous reflex) - the CNS can control the contraction of smooth muscle around vessels and therefore the resistance, and flow of the blood 1 R∝ 4 r 2.5 2.0 1.5 - a decrease in radius by 20% increases resistance by 250% - small changes in the radius of the vessel will cause large changes in the resistance, and therefore the flow Resistance 1.0 (R) 0.5 0.0 0.8 0.9 1.0 1.1 1.2 radius (r) RESISTANCES IN SERIES - flow = electrical current - resistance in blood vessel = electrical resistance - flow of blood is effectively governed by ohm's law RESISTANCES IN SERIES R1 R2 ΔP1 ΔP1 = Flow1 × R1 - the flow through vessels R1 and R2 is the same ΔP2 ΔP2 = Flow2 × R2 ΔP = ΔP1 + ΔP2 = (Flow1 × R1 ) + (Flow2 × R2) the perfusion pressure is equal to the pressure difference between the inlet and outlet pressures, which in turn is equal to the pressure drop across both vessels = Flow × (R1 + R2) = Flow × R R = R1 + R2 exact same as resistors in series in an electrical circuit (R > R1 or R2) RESISTANCES IN PARALLEL RESISTANCES IN PARALLEL R1 R2 ΔP ΔP1 = Flow1 × R1 - the perfusion pressures are the same through both vessels are the same - but the flow will be different unless the two vessels are identical in resistance ΔP2 = Flow2 × R2 ΔP1 ΔP2 + R1 R2 - the resistance of the system is lowered by having vessels in series Flow = Flow1 + Flow 2 = ⎛1 1⎞ = ΔP ⎜ + ⎟ R1 R2 ⎠ ⎝ 1 1 1 = + R R1 R2 (R < R1 or R2) THE HEART THE HEART Fig. 12.06 Endocardium (endothelium) Fig. 12.06 - CHAMBERS THE FOUR CHAMBERS OF THE HEART LEFT ATRIUM RIGHT ATRIUM LEFT VENTRICLE RIGHT VENTRICLE Fig. 12.06 – VESSELS THE GREAT VESSELS right pulmonary artery two they are the largest vessels - they must be able to carry the total cardiac output - flow = area * velocity - large area, high velocity --> large flow - large diameter lowers resistance - 8 great vessels in total right pulmonary veins aorta left pulmonary artery left pulmonary veins two superior vena cava drains head, upper body pulmonary trunk inferior vena cava drains abdominal cavity, legs VERTICAL SECTION VERTICAL CROSS-SECTION THROUGH HEART INTER-ATRIAL SEPTUM RA muscle, myocytes RIGHT VENTRICULAR FREE WALL generates a pressure that is 10 times less than the left ventricle generates very high pressure about 100 mmHg LEFT VENTRICULAR FREE WALL fat, fibrous tissue Hurst’s The Heart INTER-VENTRICULAR SEPTUM HORIZONTAL SECTION CROSS-SECTION THROUGH VENTRICLES INTER-VENTRICULAR SEPTUM RIGHT VENTRICULAR FREE WALL LEFT VENTRICULAR FREE WALL Hurst’s The Heart right ventricle = “flap” on the cylindrical left ventricle Fig. 12.06 – VALVES CARDIAC VALVES atrioventricular valve TRICUSPID VALVE MITRAL VALVE (BICUSPID VALVE) AORTIC VALVE PULMONIC VALVE Fig. 12.07a THE CARDIAC VALVES all the valves are more or less in a single plane fibrous ring semilunar valves - look like a half moon - aortic and pulmonary - separates the muscle of the atria from the muscle of the ventricle - impenetrable to electrical current - acts as an insulator two leaflets three leaflets Fig. 12.07b PULMONARY VALVE PAP MUS & CHORD TEND PAPILLARY MUSCLES & CHORDAE TENDINAE RA CHORDAE TENDINAE made of connective tissue - tendinous chords - pull on the leaflets of the atrioventricular valve - close it on contraction of the ventricle PAPILLARY MUSCLE muscle that sticks from in the free wall Hurst’s The Heart PAP MUS & CHORD TEND PAPILLARY MUSCLES & CHORDAE TENDINAE atrioventricular valve - when the ventricle contracts, high pressure is generated, and the chordae tendinae pull the atrioventricular valves closed - after MI, the myocytes of the heart die, cannot generate a large pressure in the ventricle chordae tendinae Hurst’s The Heart Fig. 12.06 - endocardium - epithelial layer that lines the inner surface of the atria and ventricles - the outside of the heart is also lined with an epithelial later, epicardium - the epicardium is stuck to the muscle of the heart - pericadial sac, tough sac that keeps the heart in place on contraction - outer two layers of the pericardial sac are glued together Endocardium (endothelium) Table 12.01 atrial fibrillation - extremely common in older people - quivering of the atria - can live with it - the atria are not completely essential - arterioles - constrict to regulate the flow of blood to an organ and controlling blood pressure - all vessels are lined with a layer of endothelial cells, capillaries are only a single layer Fig. 12.08 WILLIAM HARVEY WILLIAM HARVEY (1628 A.D.) De Motu Cordis (On the Motions of the Heart) discovery of circulation http://www.uh.edu/engines/epi1992.htm IBN AL-NAFIS (~1250 A.D.) may have discovered circulation earlier ELECTRICS ELECTRICAL SYSTEM OF THE HEART electrical currents are transduced into mechanical contraction ELECTRIC - Etymology Oxford English Dictionary amber - when rubbed, can generate static electricity http://www.thebakken.org/artifacts/friction.htm Fig. 12.10 ACTIVATION SEQUENCE OF THE HEARTheart is cardiogenic - our (unlike insects which have a neve that stimulate contraction) - S.A. node - close to where the superior vena cava meets the right atrium - natural pacemaker of the heart - cells are spontaneously active - action potential propagates from cell to cell out the sinus node from the right atrium to the left atrium - the fibrous ring cannot produce action potentials - the current stops when it meets the fibrous ring - the A.V. node penetrates the fibrous ring - action potentials travel slowly through the A.V. node and into the bundle of his - the bundle of his splits into two bundle branches - each bundle branch splits into many smaller branches - simultaneously action potentials travel down the two bundle branches and into many smaller fibers, Purkinje fibers which make contact with the muscle S.A. node, A.V. node, Purkinje fibers are muscle cells, they are not neurons Fig. 12.09a INTERCALATED DISC specialized junction where the ends of cardiac cells come together - appears to be straight, but has an undulating, winding structure - hold gap junctions ~100 μm - atrial and ventricular cells tend to have a cylindrical shape Fig. 12.09b nexus = gap junction NEXUS – GAP JUNCTION NEXUS or GAP JUNCTION the ISF is almost obliterated - gap junction plasma membrane - ISF between membranes of adjacent cells CONNEXONS CONNEXONS or HEMI-JUNCTIONS connexin - 6 of them assemble a connexon gap junctions provide a pathway for electrical conducting ions to flow between adjacent cells - anything less than 1000kDa can pass through - ions, ATP two connexons form one gap junction LOCAL CIRCUIT CURRENTS LOCAL CIRCUIT CURRENTS - cardiac cells tend to rest at a potential of -80 or -90mV - any positive ion will move from the depolarized cell into the resting cell - negative ions will move the other way - the action potential will move into the adjacent resting cell - sodium ions will tend to move opposite to potassium - local circuit current --> this current flowing in the ISF is what is picked up by ECG - both currents flowing in and outside of the cell are necessary for propagation of the action potential intercalated disk, gap junctions Both intra- and extra-cellular flow of current necessary for propagation to occur THE ECG THE ELECTROCARDIOGRAM - tracing of the electrical activity of the heart ECG EKG “kardio” is not the German word for heart: elektrokardiogram electrocardiograph = ??? the machine ECG HOOKUP ECG SET-UP - measure electrical currents that flow outside of the cells in the heart - extracellular recording patient cable lead-selector switch must select which leads are connected to the plus and minus terminals of the voltmeter + ─ VOLTMETER ECG •ECG is an extracellular recording •voltage = potential difference •zero = RL reference lead, ground lead --> right lead similar to how zero is atmospheric pressure in respiration TYPICAL ECG TYPICAL ECG heart rate is probably about 70, the heart cycle is slightly less than 1 second http://www.mf.uni-lj.si/mmd/cardio-a/eng/sz-00/sldr00001.html 1 second 1 big square = 0.2 seconds 5 big squares = 1 second Fig. 12.14a ECG WAVES and COMPLEXES QRS complex R-wave P-wave T-wave Q-wave S-wave amplitude ≈ 1 mV (vs. 100 mV for an intracellular recording) the extracellular signal is 100 times smaller than if you were to record the voltage drop across the inside of the cell - by the time the currents reach the skin, they become much smaller Fig. 12.11 ACTIVATION SEQUENCE AND ECG P - action potentials generated in the SA node - just before P wave - see nothing because the current generated is extremely small - it is lost in the noise of the recording - an electrode must be fed directly into the right atrium - potentials enter the AV node and travel very slowly through it R T S - repolarization - action potentials invade the muscle right atrium - first half, the potential spreads through the right atrium - second half, the potential spreads through the left atrium Q - potentials enter the bundle of his and go through the bundle fibers and purkinje fibers - still see nothing - the QRS complex is caused by ventricular activation (left and right ventricular walls and ventricular septum) LEADS LEAD 1. Electrode itself: e.g., RA lead 2. Combination of electrodes taken to the voltmeter: e.g., lead I BIPOLAR LIMB LEADS BIPOLAR LIMB LEADS - there are 12 leads recorded in a typical ECG - turning the lead selector switch to lead 1 will connect lead 1 to the voltmeter - leads are bipolar because they record the voltage difference between the two leads I = LA-RA II = LL-RA III = LL-LA the right leg is implicit 12-LEAD ECG the minus terminal is connected to the ground, the positive lead is the exploring lead THE CLINICAL TWELVE-LEAD ECG I V1 V = unipolar lead do not memorize details on pg. 401 no P-wave II V2 looking at the heart from the wrong angle III V3 RS complex - each lead looks at the heart at a different angle - each voltage vector points in a different direction - the last 9 leads are unipolar leads - depending on the lead you are looking at you may or may not see the typical waves inverted T-wave aVR V4 Q-wave only aVL V5 aVF V6 D.J. Rowlands, “Understanding the Electrocardiogram”, 1981 ACTION POTENTIALS ACTION POTENTIALS Fig. 12.12a VENTRICULAR ACTION POTENTIAL plateau fast upstroke - high concentration of Na+ channels in the heart upstroke most nerves rest at about -65mV repolarization much wider than a nerve action potential --> very long action potential resting potential N.B. duration much longer than nerve or skeletal muscle Fig. 12.12 IONIC BASIS UNDERLYING THE VENTRICULAR AP Ca++ ions enter the cell - the reason the potential changes is due to ionic flow across the membrane - the bilayer itself is a very good insulator - ion channels allow for the flow of ions from one side of the membrane to the other K+ current leaving - there are at least 20 different types of channels in the heart, each the cell characteristic for a different ion - the foot of the action potential cell is due to the local depolarization of the cell and the action potential wave front which propagates through the cell - on depolarization Na+ enters the cell, moving along the concentration and voltage gradient Na+ currents enter the cell log scale Na+ channels immediately inactivate after depolarization - the peak should be narrower cell is polarized at rest INa: the fast inward Na+ current at rest: PK >> PNa , PCa so: V ≈ EK IK1, IKs, IKr, IKur, Ito, … there are at least 10 different K channels that open and close at different parts of the cardiac cycle 2 different Ca CaL CaT currents: L=long T=transient I ,I the activation and inactivation of Ca++ channels is similar to Na+ channels, but they acticate and inactiate much more slowly Fig. 12.13a SINUS NODE ACTION POTENTIAL no resting membrane potential! - sinus cells never rest - the voltage never stops changing - the gradual depolarization during the resting phase of the heart called the pacemaker potential - spontaneous diastolic depolarization - there is no plateau - the upstroke is very slow - there are no Na+ channels - the slow pacemaker potential eventually begins to open Ca++ channels pacemaker potential, spontaneous diastolic depolarization Fig. 12.13 IONIC BASIS UNDERLYING THE SA NODE AP What makes the sinus contract? --> pacemaker potential - Na+ permeability is decreased - pacemaker current, If - it is activated when the current hyperpolarizes - channels are permeable to both Na+ and K+ - the increase in the permeability of the If current helps to depolarize the cell pacemaker current: If (Na+ and K+) No INa Fig. 12.14b FAST and SLOW APs 1−10 V/sec “slow” conduction velocity SA node AV node 0.01-0.05 m/sec slow upstroke velocity causes a slow conduction velocity “fast” due to large Na+ sodium channel concentrations 100− 1000 V/sec 0.5-5 m/sec ventricular muscle atrial muscle bundle of His Purkinje fibre Fig. 12.14 ECG and VENTRICULAR AP depolarization wave - atrial upstroke during the p wave and repolarization somewhere in the QRS wave - atrial action potential is much shorter than a ventricular action potential but it is still much longer than a nerve action potential - between the P and QRS action potentials are moving slowly through the AV node --> long pause in potential - right at the beginning of the Q wave, potentials are travelling through the bundle of his, bundle branches and purkinje fibers repolarization wave - the activation (upstroke) of the first cell in the ventricle is right at the beginning of the QRS complex - the last cell of the ventricle depolarized at the end of the T wave - other cells of the ventricle are depolarizing at different times When does the atrial action potential occur? Why is the PR segment so long? CARDIAC ARRHYTHMIAS CARDIAC ARRHYTHMIAS Fig. 12.16 NORMAL SINUS RHYTHM NORMAL SINUS RHYTHM at a normal rate, rhythm starts in the sinus QRS 1 second P T http://www.mf.uni-lj.si/mmd/cardio-a/eng/sz-00/sldr00001.html can be pathological or physiological sinus bradycardia: rate < 60/min sinus tachycardia: rate > 100/min sinus arrhythmia: on inspiration, rate ↑ on expiration, rate ↓ the activation sequence of the heart remains the same, the SA node is just firing more often 2:1 AV BLOCK 2:1 ATRIOVENTRICULAR BLOCK - if the block in the AV node it is normally not a huge problem - if the block is in the bundle of his or the bundle branches it is frequent that the patient will go into complete block --> pacemaker - there has been a block somewhere between the atria and ventricles - the sinus node is working as it should - there was a block of conduction on the second, fourth, sixth etc. contraction - two contraction of the atria for every 1 contraction of the ventricle QRS: http://sprojects.mmi.mcgill.ca/heart/ecg990831e2.html P: the block could be in the AV node, bundle of his or both of the bundle branches at the same time location of block = ??? why problematic? this will cause the cardiac output to be cut in half - eventually could result in a complete block COMPLETE AV BLOCK COMPLETE ATRIOVENTRICULAR BLOCK - normally the only pacemaker you see in the heart is the SA node - some people will have a subsidiary pacemaker that will come up under the conditions of complete ventricular block - the rate of the subsidiary pacemaker will vary from one person to another - the purkinje fibers have the ability to become spontaneously active - it looks like the subsidiary pacemaker is somewhere in the ventricles, in the purkinje fibers QRS: P: T http://sprojects.mmi.mcgill.ca/heart/ecg990802r2.html subsidiary pacemaker where is the second pacemaker? electronic pacemaker PVC PREMATURE VENTRICULAR CONTRACTION 5:22 p.m. Hinkle et al., 1977 ectopic beat ectopic pacemaker - before the T wave is over there is a large deflection - it came earlier than it should have --> premature beat coming from the ventricles - ectopic pacemaker - a pacemaker is somewhere where it should not be (in this case ventricle) - this patient has a cardiac ischemia PVC → VT VENTRICULAR TACHYCARDIA and FIBRILLATION 5:25 p.m. - no longer an isolated PVC - there is a rapid run of ventricular contractions - heart rate of about 300beats/second - there is no blood being pumped out of the heart - the blood pressure is likely 0 - ventricular tachy - very fast heart beat in the ventricles - the beat originates in the ventricles, does not originate in the SA node Hinkle et al., 1977 PVC ventricular tachycardia ventricular fibrillation VT → VF VENTRICULAR TACHYCARDIA → V. FIBRILLATION vtach degenerates into ventricular fibrillation after a few seconds 0.2 s coarse vfib fine vfib 0.5 mV Goldberger, 1999 treatment? cardioversion defibrillation - electrical therapy is used for both ventricular fibrillation and tachy - for tachycardia a smaller cardioversion will be given vs. a large defibrillation for a fib SCAR VT REENTRANT VENTRICULAR TACHYCARDIA - heart cells and brain cells are nonregenerating - this patient had an MI - scar tissue replace the heart muscle that died - this is the apex of the heart - a 'sock' with many electrodes is placed over the heart and they will pick up all the various signals happen and where they happen - black dots - at a give time, the activation wave front of the heart there --> wave front is circulating around the scar tissue - the wave from continues to move around the scar tissue --> vtach - the only reason the patient has a vtach is because the action potential must move around an anatomical barrier circus movement reentry - need an anatomical obstacle - the wave front must move around and re-enter the movement on the other side of the obstacle scar tissue Winfree, 1987 (data of Downar et al., 1984) breakup → fibrillation MINES George Ralph Mines (1886-1914) - first to study circus movement reentry - was the physiology professor at mcgill - Mines – Stokes-Adams Mines ECG (1914) Xu’s MOVIE COMPUTER SIMULATION OF REENTRY IN ISCHAEMIC VENTRICULAR MUSCLE SPIRAL-WAVE REENTRY www.medicine.mcgill.ca/physio/guevaralab Xu’s MOVIE COMPUTER SIMULATION OF REENTRY multiple spiral waves in IN HOMOGENEOUS MUSCLE - perfectly homogenous sheet - there is no obstacle, every cell on the sheet is identical - spiral wave re-entry - there is a re-entrant motion despite the presence of any obstacle - this is likely to happen in some one who is younger and healthier - a person who has a circus reentry obstacle can break up into spiral wave fronts all over the myocardium - a normal wave front is planar the ventricle - vfib SPIRAL-WAVE REENTRY red - depolarized blue - polarized www.medicine.mcgill.ca/physio/guevaralab activation wavefront - the interface between the cells that are depolarized and the ones that are polarized Fig. 12.17 EXCITATION-CONTRACTION COUPLING electro-mechanical coupling - calcium ion move in through calcium ion channels on depolarization of the membrane and bind to a ryanodine receptor on the sarcoplasmic reticulum - the SR is full of calcium so when it opens, lots of calcium is released into the cytoplasm - 95% of the calcium in the cytoplasm is from the SR, it increases 1000x - calcium induced calcium release - the binding of calcium to troponin on the myosin strand allows for contraction Fig. 12.18 (parallels internal [Ca++]) - there is a delay between the onset of the action potential and the generation of force - the mechanical event occurs significantly after the action potential - it takes some time to activate the calcium channels and the diffusion of ions to troponin - the peak of force is usually around the time of repolarization Mechanical activity lags behind electrical activity: the invasion of the ventricle by the action potential is not when it contracts activation ≠ contraction electro-mechanical dissociation you see QRS complexes in the ECG (there are action potentials) but there is no contraction of the heart, no pulse, something is happening between the membrane and the contractile unit THE CARDIAC CYCLE THE CARDIAC CYCLE Fig. 12.19a SYSTOLE - as soon as the pressure in the ventricle is higher - ventricles start to contract than in the pulmonary artery, the blood will flow - as soon as the ventricle contract, there is a rise in pressure out - ventricular ejection - the pressure in the ventricle is higher than in the atria, as a result the - opening of the semilunar valves atrioventricular valves close - when the ventricle is contracting, the volume of water is unchanged - isovolumetric Fig. 12.19b - A DIASTOLE - the atria are slowly filling up - when the pressure in the ventricle drops after ejection, it is lower than in the aorta/pulmonary trunk as a result the semilunar valves close - both valves are closed for a short period of time - for this short time, the volume of blood in the ventricle is fixed - isovolumetric Fig. 12.19b - B - the pressure in the ventricle falls to an extremely low pressure - the pressure in the atria will then be higher than that of the ventricle - as a result the atrioventricular valves open - the SA node fires some time after the passive filling of the heart DIASTOLE AV valves: Aortic and pulmonary valves: - atrial kick - fill the ventricles with even more blood Fig. 12.20b MC AO AC MO LEFT HEART small boost in volume from atrial contraction AORTIC PRESSURE - the pressure in the ventricle is low until the action potentials invade and it starts to LEFT VENTRICULAR PRESSURE contract - the pressure in the ventricle is always slightly lower than the pressure in the LEFT ATRIAL PRESSURE atrium - almost as soon as the ventricle starts to contract, the pressure exceeds that of the atria - VENTRICULAR VOLUME LEFTatrioventricular valve close - phase 2 - both valves are closed - after contraction, the pressure in the ventricle will begin to fall to the point where it is below that of the aorta/ pulmonary artery - the semilunar valves close. phase 4 (both valves are closed again) - when the pressure in the ventricle dips below ECG that of the atria, the atrioventricular valves open - phase 1, filling of the ventricles - the atria contract, giving a small boost in HEART SOUNDS ventricular volume - SA node fires action potential - the ventricle proceeds to contract and when the pressure in the ventricle exceeds that of the atria, the atrioventricular valves close and the cycle continues http://w3.uokhsc.edu/human_physiology/wiggers1/index.htm Wigger’s diagram - when the valves close, they touch each other - waves are transmitted through the blood, making a sound first sound - mitral and tricuspid closing - the second heart sound is the closing of the semilunar valves End diastolic volume End systolic volume SV, EF, CO STROKE VOLUME, EJECTION FRACTION, CARDIAC OUTPUT STROKE VOLUME = END DIASTOLIC VOLUME − END SYSTOLIC VOLUME how much blood is pumped out with each contraction SV = EDV − ESV SV = 120 mL – 50 mL = 70 mL EJECTION FRACTION = STROKE VOLUME/END DIASTOLIC VOLUME EF = SV/EDV EF = 70 mL/120 mL = 0.6 (60%) CARDIAC OUTPUT = HEART RATE × STROKE VOLUME CO = HR × SV CO = 70 min-1 × 70 ml = 4900 mL min-1 = 5 L min-1 Fig. 12.21 RIGHT HEART - in the right ventricle the peak pressure is 5 times lower than the left heart - the pattern of contraction is the same as the left heart but the pressures are much lower Pulmonary artery pressure Right ventricular pressure TC PO PC TO Fig. 12.25 STARLING’S LAW OF THE HEART (FRANK-STARLING MECHANISM) ↑ EDV produces ↑ SV - the more the ventricle is filled with blood, the more it stretches, the more blood it will expel - it contracts more forcefully “pre-load” = EDV, Pra, … VALVULAR MURMURS VALVULAR MURMURS Fig. 12.22a NORMAL VALVES Fig. 12.22b ABNORMAL VALVES - the blood regurgitation causes turbulent blood and makes sound waves which can be heard - a stenotic valve is lower in diameter, so the blood must increase in speed in order to maintain flow BLOOD PRESSURE SYSTEMIC ARTERIAL BLOOD PRESSURE (BP) one of the 4 vital signs temperature, rate of respiration, heart rate BP WAVEFORM ARTERIAL BLOOD PRESSURE AORTIC PRESSURE why are arteries elastic? LEFT VENTRICULAR PRESSURE systolic pressure the highest pressure diastolic pressure resting pressure Pulse pressure = systolic - diastolic pressure mean arterial pressure (MAP) ≅ diastolic pressure + 1/3 (pulse pressure) ≅ 100 mm Hg BP MEASUREMENT MEASUREMENT OF BP DIRECT INDIRECT Palpation Auscultation Oscillometry DIRECT METHOD DIRECT METHOD Stephen Hales (1733) is still done, but using an arterial catheter ANEROID SPHYGMOMANOMETER ANEROID SPHYGOMANOMETER BP cuff aneroid gauge without fluid needle-valve inflating bulb ANEROID BAROMETER ANEROID GAUGE the pressure here is the same as in the tube - an increase in pressure will cause the lever to be pushed down http://www.bartleby.com/61/60/A0296000.html MERCURY SPHYGMOMANOMETER MERCURY SPHYGOMANOMETER the hydrostatic pressure is the pressure at the bottom of the column - measured directly mm Hg PALPATION - A METHOD OF PALPATION PALPATION - B - if the cuff is pumped to a very high pressure, 200mmHg, arteries will collapse - the pressure in the cuff starts to decrease - right at the point where the pressure in the cuff is lower than the systolic pressure, the pulse will return - can only measure the systolic pressure - method of palpitation --> uses touch AUSCULTATION METHOD OF AUSCULTATION KOROTKOFF SOUNDS KOROTKOFF SOUNDS Korotkoff sounds - when the pressure in the cuff is greater than max systolic pressure, the vessel is occluded - as the pressure in the cuff decreases to the point where the pressure in the cuff is lower than in the artery, flow will resume and the blood will move around causing turbulence - you can hear sounds when the blood just starts moving - you hear sounds all the way until the cuff pressure is lower than diastolic pressure - when full blood flow returns however you do not hear anything because blood flow is laminar - when the vessel is patent, and no longer occluded, sounds disappear OSCILLOMETRY OSCILLOMETRY nominal BP: 120/80 mm Hg WHY CONTROL BP? WHY IS BLOOD PRESSURE IMPORTANT? WHY DOES BP HAVE TO BE REGULATED? WHY BP IMPORTANT? Pa ORGAN Pv Pa - Pv ΔP MAP flow = = ≅ R R R increased intracranial pressure even if pressure fluctuates, organs will keep flow constant 1. Keep flow constant, despite fluctuations in Pa. e.g. exercise, despite constant flow an organ 2. Adjust flow according to need. can increase flow - changing size of arterioles 3. Minimize fluctuations in Pa. AUTOREGULATION FLOW AUTOREGULATION brain, heart, kidneys, … even if arterial pressure changes, an organ will change the resistance of the organ to maintain constant flow CORONARY ARTERIES THE CORONARY ARTERIES right coronary artery left coronary artery CORONARY AUTOREGULATION CORONARY AUTOREGULATION - experiments are performed using a coronary catheter than can decrease or increase coronary perfusion pressure - if there is a drop in perfusion pressure, a drop in flow will result - there is a reflex where the flow will return to normal in 15s despite a lower pressure - there must be a decrease in the resistance of the arterioles, they increase in diameter AUTOREGULATION RANGE AUTOREGULATORY RANGE the immediate decrease in flow at very high or low pressures, small changes cause large changes in pressure - similar to a buffer autoregulatory range large changes do not lead to as big changes in flow Fig. 12.34b TWO MECHANISMS OF AUTOREGULATION metabolic - build up of waste products cause a decrease in contraction of vessels causes a decrease in resistance myogenic - all reflexes eventually break down at the extremes - there is only a certain range of 'stretchiness' that a vessel has - the decrease in pressure in the arterioles causes a decrease in the diameter of the vessel - the transmural pressure (pressure inside minus the pressure outside the vessel) falls and the arteriole collapses to a smaller size - similar to blowing up a balloon - smooth muscle will sense the decrease in vessel diameter, and by itself cause a decrease in resistance - it is intrinsic to the smooth muscle Fig. 12.34a LOCAL METABOLIC CONTROL - the flow of blood to the heart can increase from the resting value by a factor of 5 on exercise - hyperventilation - rapid deep breaths - decrease in PCO2 - will cause a constriction of arterioles - decrease in flow of blood to the brain - breathing into a paper bag - CO2 re-breathing will increase metabolite concentration in the blood and decrease arteriole constriction exercise = similar to a increase in flow accumulation of waste products cause a relaxation of smooth muscle around the arterioles •Flow adjusts to metabolic need: [active] hyperemia •Skeletal muscle, cardiac muscle, brain, … seizure, ‘brown-bag’ technique Fig. 12.36 NEURAL – HORMONAL – LOCAL CONTROL Endothelial cells ↑ NOT lungs Viagra™ TPR TOTAL PERIPHERAL RESISTANCE (SYSTEMIC VASCULAR RESISTANCE) Pra MAP R= ΔP flow CO cardiac output mean arterial pressure>>>right arterial pressure TPR = MAP-Pra MAP ≅ CO CO mean arterial pressure is controlled by cardiac output and totral peripheral resistance MAP = CO × TPR (V = IR) - fainting results from decrease blood flow to the brain - can be cause by an increase in diameter of arterioles - this causes a decrease in arterial pressure and decreased flow vaso-vagal syncope Fig. 12.29 PULMONARY VASCULAR RESISTANCE PVR << TPR (1/10) if the flow in the pulmonary circulation is the same but the pressure is so much lower, then the resistance must also be lower to maintain constant flow high-P, high-R low-P, low-R NEURAL CONTROL NEURAL CONTROL OF THE HEART AND VESSELS SAN - PARASYMP PARASYMPATHETIC CONTROL OF HEART RATE - increase parasympathetic activity - increased muscle tone - more action potentials per unit of time - release of more Ach onto vagus nerve nicotinic (it is activated by nicotine) (pre-ganglionic nerve) receptor - increase activity in the post ganglionic nerve cause the release of Ach onto muscarinic (it is nicotinic receptor activated by muscarine) receptors of the SA node (ACh) - the muscarinic receptor is also a K+ channel which is immediately opened on stimulation - causes a decrease in heart rate - atropine molecules bind to muscarinic receptors competing with Ach - when it binds, it does not cause the opening of the K+ channels - causes an increase in heart rate by blocking the Ach from binding - common treatment for bradycardia medulla oblongata spinal cord post-ganglionic nerve muscarinic receptor (ACh) atropine SAN – SYMP SYMPATHETIC CONTROL OF HEART RATE - similar to parasympathetic control except the second neurotransmitter released is norepinephrine - NE binds to b-adregenic receptor which is not an ion channel - net result is the increase in heart rate β-adrenergic receptor - b-agonist works the same was as NE, binding to the receptor and activating it - b-antagonist are generally used for people with nigh blood pressure or asthma - causes a decrease in heart rate ACh = acetylcholine NE = norepinephrine (noradrenaline) β-agonist β-antagonist (β-blocker) Fig. 12.23 CHANGE IN RATE OF SA NODE sympathetic - there is a net increase in current in the SA node parasympathetic hyperpolarization of the membrane and decrease in current in the SA node INOTROPY – SYMP SYMPATHETIC CONTROL OF CONTRACTILITY increase in calcium flow into the cell --> causes an increase in contraction of the heart β-adrenergic receptor NE ACh = acetylcholine NE = norepinephrine (noradrenaline) b-agonist - increases the force of contraction of the heart - helps restore blood pressure b-antagonist - increases the force of contraction, decrease in blood pressure β-agonist β-antagonist (β-blocker) Fig. 12.27 INCREASE IN CONTRACTILITY ↑ maximal force ↑ rate the rate at which the force falls also increases - the peak value of force increase and the relaxation time decreases too - the duration of contraction decreases ↓ duration of systole Fig. 12.26 INCREASED CONTRACTILITY - as the muscle stretches, the force of contraction increases - sympathetic activity causes an increase in force of contraction and decrease in contraction time - sympathetic activation will shift the green curve up and to the right VESSELS - SYMP SYMPATHETIC CONTROL OF VESSEL TONE most of the vessels of the body are innervated by the sympathetic nervous system which release NE which binds to a different receptor, a-adrenergic receptor, that causes the muscle to constrict, increasing resistance a-agonists bind to aadrenergic receptors causing arterioles to constrict, lowering blood pressure - constricting vessels makes the TPR go up, decreasing flow a-blockers compete with NE for the alpha receptor sites, binding to them without activating them - decreases the amount of vessel constriction α-adrenergic receptor α-agonist α-blocker ADRENAL GLANDS ADRENAL GLANDS - innervated by the sympathetic system - no post ganglionic cells, not typical - NE and E are both alpha and beta agonists - bind to receptors on the SA node increase action potential activity and heart rate 2 Epi 3 1 Norepi 3 α,β α,β Fig. 12.24 AUTONOMIC CONTROL OF HEART-RATE strong b-agonist β β ACh BP CONTROL SYSTEMS BP CONTROL SYSTEMS BP CONTROL SYSTEMS BP CONTROL SYSTEMS there are many different control systems working together to control blood pressure TIME-SCALES OF BP CONTROL SYSTEMS TIME-SCALES OF OPERATION - the baroreceptor reflex acts very quickly - blood volume is ultimately responsible for the control of blood pressure - controlled by kidneys over a long period of time - different control systems work over different time scales - no reflex is perfect, they can only bring you part of the way back - reflex strength reflects how strong a reflex is - different reflexes have different strengths and work on different time scales OPERATING RANGES OF BP CONTROL SYSTEMS PRESSURE-RANGE OF OPERATION - baroreceptors only work in the middle range of arterial pressure - there is no feedback gain at very high or low blood pressures CNS ischemic response - when blood pressure decreases, there is reduced blood flow to the brain - produces vasoconstriction such that TPR increase and so does flow, increase blood supply to the brain BARORECEPTOR REFLEX THE BARORECEPTOR REFLEX Fig. 12.53 THE BARORECEPTORS - nerve terminal that senses pressure - two main baroreceptors - carotid sinus and aortic arch - buried in the wall of the carotid terminal are nerve terminals - they are mechanoreceptors that sense the amount of stretch in the wall of the artery s BARORECEPTORS AFFERENT ARC OF THE BAROREFLEX afferent arc - sensory system efferent arc - motor arc when your heart beats, there is an elastic wave travelling through the vessel, stretching the walls of the vessel - the baroreceptors sense these waves and produce action potentials and send the information to the brain - when blood pressure drops, there are fewer action potentials send by the baroreceptors to the brain a few of the fibers in the vagus nerves come from the baroreceptors Fig. 12.54 BARORECEPTOR FIRING FREQUENCY as the arterial pressure goes up there is an increased rate of baroreceptor action potential firing - below 40mmHg the reflex saturates - there are no action potentials sent - explains the feedback gain curve Fig. 12.55 ↓ ↓ ↑ ↑ HR ↑ contractility ↑ vasoconstriction ↑ venoconstriction ↓ ↑ HR K+ channels closed, depolarization CO = … MAP = … EFFECT OF REFLEX INCREASE IN HR falling BP, baroreceptor reflex increases heart rate - increased cardiac output - increased cardiac output increases mean arterial pressure, and thus heart rate CO = HR × SV ↑ ↑ MAP = CO × TPR = HR × SV × TPR ↑ ↑ negative feedback system CO = … MAP = … EFFECT OF REFLEX INCREASE IN CONTRACTILTY - decreasing contractility causes an increase in stroke volume - baroreceptor activity causes increased heart rate and increase cardiac output - an increase in stroke is achieved by increased contractility CO = HR × SV ↑ ↑ MAP = CO × TPR = HR × SV × TPR ↑ ↑ negative feedback system CO = … MAP = … EFFECT OF REFLEX VASOCONSTRICTION - increased TPR causes an increase in mean arterial pressure - works the same way as venoconstriction - on constriction the pressure on the fluid in the veins increases - works to increase venous return, venous pressure, TPR CO = HR × SV MAP = CO × TPR = HR × SV × TPR ↑ ↑ negative feedback system MAP = HR × SV × TPR EFFECT OF BAROREFLEX CO = HR × SV MAP = HR × SV × TPR vasoconstriction; venoconstriction CAROTID SINUS HYPERSENSITIVITY CAROTID SINUS HYPERSENSITIVITY start end - was in normal sinus rhythm, until the cartid sinus was massaged --> asystole - the sinus may be hypersensitive - the massage was enough to make the baroreceptor fire tons of action potentials to make the brain think that the blood pressure is high --> it will decrease the heart rate by activating the parasympathetic system causing a huge outflux of K+, hyperpolarizing the cell … http://www.syncope.co.uk/csh_asystole.htm rapid onset of effect electronic pacemaker a pacemaker will sense normal activity, and can inject electronic current into the heart when there is high baroreceptor activity BARO-DENERVATION BARORECEPTOR DENERVATION - spontaneous fluctuations in arterial blood pressure - in the absence of baroreceptors, the pressure is very labile, changes a lot - the blood pressure can get to extremely high blood pressures, so high that the bronchioles cannot take it - there can be patients who have tumors in the carotid body, near the baroreceptors - radiation therapy can damage the receptors and lead to an MAP like this - the baroreceptor is very important for the beat to beat heart pressure control MAP unchanged baroreceptor nerves are cut at the carotid sinus and at the aortic arch neck tumours nosebleed “buffer reflex” LONG-TERM BP CONTROL LONG-TERM CONTROL OF MEAN BP Fig. 12.57a KIDNEYS, BLOOD VOLUME, AND BP the kidney has the ability to alter the amount of fluid filtered into urine based on blood pressure - an increase in pressure results in a greater loss of fluid MAP = CO × TPR CO = HR × SV Frank-Starling mechanism the amount of blood being returned to the right atrium falls arterial pressure in the kidneys goes up ↑ pressure diuresis ↓aldosterone involved in water retention in the kidney increase of fluid loss causes a decrease in plasma and blood volume **the opposite control also happens in the case of low blood pressure** RAA SYSTEM THE RENINANGIOTENSINALDOSTERONE (RAA) SYSTEM RAA SYSTEM RAA SYSTEM ACE - angiotensin II binds to receptors on arteriolar smooth muscle causing contraction - it is a potent vasoconstrictor - this causes an increase in TPR and increase in blood pressure, a negative feedback system ACE angiotensin II converting enzyme kidney cells sense the fall in pressure and release Renin, an enzyme into the blood which cleaves the precursor of angiotensis, angiotensinogen blood pressure falls - pressure in the renal arterials fall as well - angiotensin II stimulates the excretion of anti diuretic hormone - ADH causes water retention at the kidney, increase blood volume and therefore blood pressure ACE ACE - angiotensin II causes the release of aldosterone by the adrenal glands - causes the conservation of salt and water at the kidney RAA SYSTEM RAA SYSTEM - ACE inhibitor - inhibiting the action of ACE will lower the amount of circulating angiotensin II - anti hypertension drug - AT-II receptor blockers - competitively inhibits the binding of angiotensin II to receptors on smooth muscle - Renin inhibitors - inhibiting renin makes for less angiotensin I and II being synthesized ACE INHIBITORS AT-II-RECEPTOR BLOCKERS RENIN INHIBITORS AN APPLICATION AN APPLICATION: OTHOSTASIS R ortho - straight stasis - standing EXERCISE: Friday, Feb. 22nd see Dr. Lauzon’s notes ORTHOSTASIS -0.75 -0.5 despite the increase in contractility +1.5 the flow of blood to the nonessential parts of the body is decreased when the baroreceptor reflex is activated - they vasoconstrict with unchanged pressure, flow will decrease - happens everywhere except the brain and heart - cases an increase in the TPR to 4/3 of the original value - when you stand up your systolic pressure will fall, diastolic will go up a little and MAP will be unchanged - when you stand your blood pressure falls a little bit, but the baroreceptor reflex acts within seconds - bp falls because of gravity - when you stand up you drain 300-400mL of blood from your central blood volume - the blood leaves the thorax and drains into the veins of your legs and abdomen - causes an expansion of the veins and cooling of the blood - venous return decreases - the pressure in the right atrium decrease to about 0 because it is less full - the ventricles are less filled and pump out less - the contractility of the heart is decreased causing a decrease in stroke volume - when the stroke volume drops to half its normal volume then the cardiac output will also fall by a factor of a half - there is an increase in heart rate because of the baroreceptor reflex is activated, increasing heart rate and contractility - the sympathetic system and breceptors are activated increasing the strength of contraction, contractility - if this wasnt working, SV would drop more than 50% time (mins) × 0.75 × 0.5 ↓ SV: How CO preserved? CO = HR × SV ↓PP ⇐ ↓SV ×0.75 ×0.5 Despite ↑ contractility ×1.5 ↓ CO: how MAP preserved? MAP = CO × TPR ×0.75 MAP = CO × TPR FAINTING SOLDIER ORTHOSTATIC or POSTURAL HYPOTENSION ♔ standing can lead to the pooling of blood in the legs - can lead to vasovagal syncope - guards are taught to contract calf muscles acts as a pump TILT-TABLE TESTING TILT-TABLE TESTING for AUTONOMIC DYSFUNCTION http://www.syncope.co.uk/ VENOUS VALVES VENOUS VALVES Harvey (1628) Fig. 12.45 MUSCLE PUMP contraction of the muscle causes the opening of the venous valve increase flow of blood back to the heart on exercise muscle contraction causes the increase in venous return to the heart and ultimately CO MUSCLE PUMP IN ORTHOSTASIS MUSCLE PUMP IN ORTHOSTASIS also important in exercise Fig. 12.60 VENOUS PRESSURE WHILE STANDING - compressing the calf muscles or walking keeps the pressures in the veins low when you are standing up ANKLE VENOUS PRESSURE when you stand for a long time, the venous pressure in the legs is very high walking and compressing muscle pumps pushes venous blood back to the heart, reducing pressure Valvular incompetence → venous hypertension → oedema → … → ulceration Fig. 12.42 STARLING FORCES - when venous pressures in the legs increase, then filtration of plasma into the ISF will increase - the starling forces will favour filtration of ECF fluid out of the vessels there is a net loss of 4L of fluid from the plasma to the ISF 4 L per day lymph Fig. 12-47 LYMPHATIC SYSTEM ~4 L per day fluid filtered from the blood is returned by the lymphatic system Fig. 12-48 ELEPHANTIASIS accumulation of ISF because of a parasite blockage of the lymphatic system REGIONAL CIRCULATIONS THE REGIONAL or SPECIAL CIRCULATIONS SERIES-PARALLEL SERIES-PARALLEL SYSTEM 5 mm Hg 100 mm Hg Table 12.05a THE REGIONAL CIRCULATIONS the heart extracts about 60% (12mL) of oxygen from the blood compared to skeletal blood which extracts about 5mL of 20mL of oxygen from the blood must increase flow when oxygen consumption increases - cannot increase oxygen extraction (left ventricle) at exercise skeletal muscle can extract 15mL of oxygen from the blood - can increase oxygen extraction the blood goes through two capillary beds in series - increase oxygen extraction Table 12.05b THE REGIONAL CIRCULATIONS (cont’d) brown bag technique low resistance, therefore low pressure to maintain MAP the lungs to not dilate when PCO2 increases like the rest of the body - they constrict instead in order to shunt the blood to an area of the lungs that are more ventilated and not suffering from alveolar hypoxia PATHOPHYSIOLOGY PATHOPHYSIOLOGY 1. 2. 3. 4. HEMORRHAGE HYPERTENSION CORONARY VESSEL DISEASE HEART FAILURE HEMORRHAGE HEMORRHAGE Fig. 12.52 IMMEDIATE EFFECT OF HEMORRHAGE frank-starling Fig. 12.56 ACUTE RESPONSE TO HEMORRHAGE CO = HR•SV MAP = CO•TPR Fig. 12.57b CHRONIC RESPONSE TO HEMORRHAGE ↓ ↓ ↓ ↑ takes several hours, or even days to restore blood volume by decreasing water loss at the kidneys ↓ ↓ ↓ ↓ pressure diuresis RAA ↓ Figs. 12.42a, 12.59 CAPILLARY FLUID SHIFT ↓BP → ↓ arteriolar pressure - starling forces are changed from being net outward from the capillaries to being net inward - fluid is sucked back into the vessels - this is not mediated by hormones, neural response less fluid is filtered out into the ISF HYPERTENSION HYPERTENSION EPIDEMIOLOGY RANGE OF BP as you get older, systolic and diastolic blood pressures rise the mean of systolic pressure is about 120 and the diastolic is about 80 nominal blood pressure: 120/80 mm Hg systolic blood pressure > 140 mm Hg or diastolic blood pressure > 90 mm Hg borderline hypertension pre-hypertension “White-coat” hypertension N.B. old data years ago, hypertension was defined at a higher level Anti-hypertensive drug market: U.S.$ 10 billion per annum BP – GENDER & AGE BP – GENDER & AGE Canada (1986-90) 160 ΔV ΔP - males tend to have higher blood pressures than females early in life - later in life values seem to equalize Pressure (mm Hg) 140 120 100 80 60 compliance = compliance = ΔV ΔP ♂ ♀ ♂ ♀ 15-24 25-34 35-44 45-54 systolic BP diastolic BP 55-64 65-74 75+ - pulse pressure decreases when you stand up because your stroke volume decreases - the larger SV, the large the pulse pressure - another determinant is the thickness of the aorta, how compliant it is - a stenotic aorta will make for a larger SV Age (years) 1. ♂ > ♀ 2. pulse pressure ↑ with age: arteriosclerosis ΔV pulse pressure determined (a) compliance ( ) ΔP (b) SV (orthostasis) HT FACTS BASIC FACTS ABOUT HYPERTENSION •Nearly one in three adults has high blood pressure (systolic BP >140 mm Hg or diastolic BP > 90 mm Hg or presently on anti-hypertensive medication). •Of all people with high blood pressure, 28% don't know they have it (“the silent killer”), 10% aren't on therapy (special diet or drugs), 27% are on inadequate therapy, and only 35% have adequate control of BP (U.S.A.). •The cause of 90-95 percent of the cases of high blood the 5-10% have pressure is unknown (“essential hypertension”). hypertension for some •High blood pressure is easily detected and usually controllable. other reason - e.g. renal hypertension, stenosis of the renal artery Heart Disease and Stroke Statistics 2007, American Heart Association AWARE HT % OF POPULATION IN CANADA AWARE THAT HYPERTENSIVE did not do Onysko et al., 2006 UNTREATED HT % OF AWARE HYPERTENSIVE SUBJECTS UNTREATED IN CANADA did not do Onysko et al., 2006 CORONARY HEART DISEASE CORONARY HEART DISEASE coronary vessel disease, coronary artery disease, coronary disease, heart disease, … Fig. 12.66a ATHEROSCLEROSIS left and right coronary arteries ATHERO PLAQUE ATHEROSCLEROTIC PLAQUE fibrous cap - can break or rupture Atherosclerotic plaque fat globules, smooth muscle, cholesterol Lumen reduced (stenosis) - reduced cross sectional area --> increase in radius - a decrease in radius by 1/2 causes an increase in resistance by 16 - makes for flow limitation CORONARY THROMBUS CORONARY THROMBUS when the fibrous cap of the coronary artery ruptures, platelets are exposed to damaged tissue --> clot formation Hansson, 2005 Fig. 12.66 - STENOSIS CORONARY ANGIOGRAPHY stenosis angina coronary thrombosis myocardial infarction STENOSIS death of cardiac muscle thrombolysis = fibrinolysis, break up the clot angioplasty (perhaps stent) bypass graft - stenosis - narrowing of the artery - there is plaque blocking the flow of blood - can cause angina at rest due to the buildup of waste products ANGIOPLASTY CORONARY ANGIOPLASTY http://medical-dictionary.thefreedictionary.com Fig. 12.66 - STENT STENT STENT HEART FAILURE HEART FAILURE 40% of hospital admissions in N. America coronary artery disease myocardial infarction cardiomyopathy (viruses, auto-immune disease, alcohol) hypertension the heart must work harder to maintain a higher blood pressure valve disease severe anemia hyperthyroidism … heart-transplant SCD-HeFT MORTALITY IN HEART FAILURE ICD placement can prevent 25% of arrhythmical deaths www.scdheft.com Fig. 12.65 HEART FAILURE - people in the first stages of heart failure will retain fluid - by frankstarling forces CO will increase - compensative heart failure - can even see edema in these patients activation of sympathetic nervous system HYPERTROPHY & DILATION HYPERTROPHY & DILATION EPIDEMIOLOGY EPIDEMIOLOGY OF CV DISEASE (40% of all deaths) ½ CHD Deaths= SUDDEN CARDIAC DEATH 2007 Heart and Stroke Statistical Update, American Heart Association MORTALITY TRENDS MORTALITY TRENDS 1974 over the last 30 years mortality due to heart disease has decreased 2002 40% 60% treatment smoking (40%), BP (10%), cholesterol (10%) CANCER vs. CVD CANCER vs. CV DISEASE did not do cure cancer ⇓ life expectancy would rise by 3 years cure major forms of CV disease ⇓ life expectancy would rise by 7 years breast cancer: 1/30; CV disease: 1/2.5 Heart Disease and Stroke Statistics 2007, American Heart Association TWIN EPIDEMIC Nature Medicine, January 2006 did not do DIABETES did not do OBESITY OBESITY Morbidity and Mortality Weekly Report, 2005 OBESITY THE OBESITY EPIDEMIC BMI > 25 BMI > 30 Smyth & Heron, “Diabetes and obesity: the twin epidemics”, Nature Medicine, Jan 2006. AGE-SPECIFIC MORTALITY TRENDS AGE-SPECIFIC MORTALITY TRENDS ♂ ♀ in the last 10 years heart disease in young people is about to increase obesity Ford et al., 2007 RISK FACTORS RISK FACTORS FOR ATHEROSCLEROSIS physical inactivity obesity diabetes high blood concentration of LDL ("bad cholesterol") or of triglycerides low concentration of HDL ("good cholesterol") - statins high blood pressure (obesity, salt in diet, inactivity, alcohol) tobacco smoking trouble managing stress aging male (women are affected more after menopause) close relatives who had heart disease or a stroke at a relatively young age ongoing inflammation http://www.panaceia-or-hygeia.com END OF CV LECTURES END OF CARDIOVASCULAR PHYSIOLOGY LECTURES March 4th: Tutorial (not a review session) Martin theatre (not Palmer) 5:00-6:00 p.m. (not 5:30-6:30) ...
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