---start physio 1.15.97--- note: we won't be expected to reproduce the equations shown in this lecture. we're discussing the cardiovascular system, as outlined in the handout. dr moore discussed electrical events of cardiac cycle; now we're discussing cardiac mechanics. all of the slides are in the handout (phew). purpose of cardiovascular system is to bring blood close to cells, facilitate exchange of gases, fluids, solutes. conveys nutrients, regulatory agents eg hormones, gases, etc. if you look at diffusion: you have a glob of water in a 100% oxygen atmosphere. the glob will absorb oxygen until it is saturated. to reach 90% saturation would take 3 hrs if diameter is one cm. if diameter is .7 mm it takes 54 seconds, and if you get down to cellular level of 7 microns, takes 5.4 msec for globule to saturate w/oxygen. so single celled organisms can handle oxygen transfer via diffusion. but in a group of packed cells, this wont' work. you need the cardiovascular system and its capillary network to bring the oxygen rich blood close to the cells, so the diffusion distance is minimized. people like to point out that electrolyte composition of blood is similar to sea water...it's like the external environment is being distributed internally. exchange process (see handout diagram). heart pumps out cardiac output and feeds into capillary bed where exchange occurs. the heart pumps out, in an animal human size, 5.8 L/min (60 million gallons lifetime). now there are two mechanisms at work: diffusion exchange and bulk flow. bulk flow is itself comprised of filtration and absorbtion. diffusion is driven by concentration gradients. bulk flow is a physical flowing of fluid across endothelium into extravascular space with solute- eg, serum flows out of vessels based on hydrostatic and osmotic forces. if pressure in capillary is greater than out, you get filtration - often at arteriolar end of capillary. but at other end of cap bed, the pressure w/in vessel has dropped, and osmotic forces cause absorption into the vessel. what kind of volumes are we dealing with here? what's filtered... approx 15 ml/min comes out of capillaries, and about .15 gr/min of protein (eg, most proteins stay in vessel). you also lose about 15 mg/min of glucose to the tissue. now, the protein goes into the lymphatics and is drained back to the right atrium. if you look at fluid exchange for diffusion - 56 L/min of fluid exchanges w/diffusion. note, this is total exchange - net exchange = 0. of the filtered fluid: 12 ml/min fluid is absorbed, and 3 ml/min is picked up by lymph. it's important that glucose diffuses, because 15 mg/min is filtered, and you use 280 mg/min glucose in your body. so by diffusion 14 gr/min diffuses out of the capillary vessel. this gives plenty. any leftover is absorbed or returned in the lymph. 11 gr/min is absorbed. diffusion, then, is most important for most systems of the body. although filtration very important in kidney. Adult cardiovascular system: schematic pulmonary circulation LUNGS / \ RIGHT HEART LEFT HEART \ / BODY systemic circulation right heart pumps to lungs, back to left; left to body, back to right. (not true in fetus) what are the characteristics of these two circulations? systemic: serves many tissues (all tissues) variable requirements many controls exist over it high pressure head (mean 100 mmHg) high resistance (that's why high pressure. output must be same as pulm.) long hydrostatic columns (heart to foot, etc) (think of giraffe reaching from grass to tree - major pressure change in cerebral vasculature would require major controls) pulmonary: serves only lung single function (gas exchange) little control low pressure head (mean 15 mmHg) low resistance short hydrostatic columns - all w/in chest pressure gradient: see handout. x axis represents distance through system from left ventricle, through arteries, caps, veins, vc, back to r heart. lower picture is mechanical analog. note that arteries are a pressure reservoir, where veins are a volume reservoir. if one side of the heart has larger or smaller output, veins can make up the difference (to a point, i presume). about 75% bv is in venous side at any given time. about 5% is in the capillary beds, and 20% is in arterial side. what about pressure? in left heart, ventricular pressure diastolic value about 7, systolic about 120. this goes into arterial tree through aorta. it goes across a valve. the aorta has pressure pulses in accordance with pumping of ventricle. you have a systolic and diastolic pressure in the aorta both well above zero. as you get closer to the peripheral arterioles, the pulse pressure INCREASES - eg, difference between systolic and diastolc pressure is greater at arteriolar end. meanwhile, mean pressure declines (or would be no flow). then there is a precipitous drop in pressure at the precapillary arterioles whch have very high resistance, which is necessary to avoid having high pressure pumping into the delicate capillaries. so when blood is pumped into aorta, kinetic energy is stored in elastic vessel wall...yadayada. Relationship between cross sectional area and velocity of flow in systemic circulation: aorta xsectional area 2-3 sq.cm. and as branching starts, you have smaller diameter, so cross sectional area doesn't really increase- it starts increasing when you get to very small arterioles. now the branching is so vast that xsectionnal area increases. capillaries have xsectional area of about 600 cm! venules about 200, arterioles about 150. all else near zero comparatively. now, volume flow is the same through the circulation. flow must always be the same - so as you narrow the diameter, velocity increases, and as diameter widens, velocity slows. this is useful, because we WANT blood to ooze along through capillaries, so there is time for exchange mechanisms (note: yes, an individual capillary is narrow, but we're talking total for all capillaries here). so blood velocity is slow through capillaries, and faster through big arteries and veins. note diagram of various capillary systems and how much of CO they get at rest. systemic circulation- coronary, brain, muscle, skin & skeleton, kidney, liver &spleen are arranged in parallel. 100% of blood enters LA and LV. this blood pumps out - 95% to systemic non-bronchial circ, and 5% to bronchial circulation (tissues of lung that are not exchange tissues, eg, bronchioles, etc.) then coronary 5% brain 15% muscle 15% skin/skeleton/etc 10% kidney (glomerular and tubular) 20% splanchnic (spleen, mesentery, stomach, int, liver) 30% [only 5% to liver first; 25% goes to spleen et al first, then enters liver via portal vein. liver good storage space and detox organ so this is good. some drugs can't be given orally because when blood drained from intestines to liver liver removes drug from blood] pulmonary circ blood returns to right heart, (from body and bronch circ) note: 3% of blood leaving bronchial circ is carried back to heart w/o going to lungs. azygous carries rest of bronchial blood back to right heart. fetal circulation will be covered later but FYI briefly in the fetus the lungs are collapsed, have very high resistance to flow.all oxygenation is via placenta, fed by placental artery. to accomodate this arrangement, anatomy changes. blood goes through PA through ductus arteriosus to aorta. also the foramen ovale between the atria causes blood to flow from R to L atrium. see handout for saturation levels. when an animal is born the fetal circulation is replaced by adult. the lungs open up, resistance drops, lungs expand, blood will try to flow back through ductus arteriosus but it will clamp down and constrict if it senses oxygenated blood flowing through it. the foramen ovale closes due to pressure gradient change. now, consider this historic perspective. veterinary medicine and animals in general have contributed a lot to our understanding of physiology. slide: cave drawing of elephant with a drawing of heart inside. Galen's view of medicine was around for about 1500 hrs. he lived about 130-201 CE and he thought the cardiovascular system - he recognized two systems, right and left heart and both pumped blood, but he thought they communicated via pores in the septum. he also recognized peripheral anastomoses. now, he thought blood flowed in and out rather than around - eg, same vessels carried blood in both directions. that view was held til the 1600s when william harvey wrote a dissertation on the anatomy and motion of heart and blood in animals. he demonstrated that there are venous valves. put tourniquet on arm and pump fist -- veins distend. you can put pressure on vein and milk blood out of vessel, and you'll get vascular collapse with a bulge proximal to it. you can basically show blood will only flow in one direction. [note: we will not be examined on the history stuff.] ---lunch break--- note: a schedule change is going to occur; we will be informed later. now..Mechanical Events of the Cardiac Cycle cont. mechanical events are preceded by electrical events in cardiac muscle. note: most of this is in someone's textbook - deighton?. exam material will only be from lecture stuff, though. slide: frontal section of heart. heart is true mechanical pump. ejects blood into the PA and Aorta. pump components: chambers and valves - valves determine the direction of blood flow. blood flows in response to pressure. if pressure is hgher in LV than in aorta, blood will flow from high to low pressure area. the valves in large vessels are semilunar. their orientation is such that they allow blood to flow from heart into vessels but not back into heart. so it depends on pressure gradient and whether valve is open or closed if you get blood valve. the mitral valve and tricuspid allow flow between atria and ventricles. again, blood follows a pressure gradient. if you take a section of heart muscle, it's made of myocytes. the myocytes are longer than they ar wide, and they tend to branch. any one cell will contact 7 neighbor cells. the intercalated disks are located at the ends of the cells and allow electrical communication between the cells (gap junctions - low resistance channels allowing ions to pass between cells - are present in intercalated disks.) the individual muscle fibers are made of myofibrils which are made of sarcomeres. myofibrils are surrounded by membranes as in skeletal muscle; both SR and Ttubular system membranes. basically as in skeletal muscle t tubules bring electrical impulse to SR to initiate ca++ release. contraction of cardiac muscle: calcium cycle to get contraction you have to release calcium from stores or bring it in from ECF to increase intracellular ca++. in cardiac muscle there are multiple mechanisms. ca++ in ECF is about a millimolar. in ICF is about .0001 mmolar. when cell is activated ICF ca++ is about .01 mmolar and ca++ binds to troponin c etc etc etc. what controls this are several pumps and exchangers. there are sodium voltage gated channels which initiate the action potential. there's also a slow inward calcium current from ca++ voltage gated channels. so ca++ and Na+ flow in. the action potential conducts down T tubular system, adn the ca++ that enteres w/AP triggers release from lateral sacs of SR - ca++ induced ca++ release. there are also pumps pumping calcium back into th SR and out of the cell. these use energy. and the sodium calcium exchanger drivees calcium out of the cell in exchange for a sodium. all of this is driven by sodium/potassium ATPase which maintains membrane excitability. if you give drugs to slow that pump, Na+ builds up in the cell slowing the na/ca exchanger so ca builds up in cell.that's why digitalis works. intrinsic contractility: due to [ca++] and sensitivity of contractile elements to [ca++] see calcium cycle page in handout. at rest, calcium level is very low, no force develops. as you approach 10 -5 or so, you start producing force. there's a graph on the handout. the curve can shift; changing contractility of heart muscle. if shifted to right, same [ca++] would produce less tension. etc. another thing that can change the force of contraction is the length. you can take an isolated muscle - eg papillary muscle- and anchor the muscle to a transducer to record tension, and hook the other end to something to stretch it out. and you record the length, measure the tension during rest and when activated. so you can generate length tension curves. see handout for graph. note that the second length generates the most force. if too short or too long, less force is generated (as discussed in prior lectures). if you plot these as tension vs length you get a length tension diagram. the peak is the active tension and the resting value is the passive tension. so you can make a pure active tension curve via subtraction (see handout). diagram: model of single cardiac myocyte, capable of generating force (note; in exp't shown above, was isometric contraction- fixed length. now if you look at the model and don't activate contractile element but change length, you change overlap of thick and thin filaments and you stretch the parallel elastic element and this produces passive force - due to an elasticity present end ot end in a muscle cell in parallel to the contractile elements. there's also something called a series elastic element in series with the contractile element. conceptually it's the parallel element responsible for the passive tension. the series element will do things to the tension as well. the contractile element must act on the world through the spring. say we had a brick on a rope in your hand, and you pull the arm up, the brick goes flying because the rope is not elastic. if you put a spring on the brick, the brick won't move until the spring is fully stretched, and finally transmits force to the brick. similar thing here. contractile elements are generating a force that has higher peak, peaks faster, and is shorter, than the actual externally percieved twitch, because of the mechanism described just above. eg, it is attenuated by the series elastic element through which the contractile element must act. in other words, you don't see what the contractile elements are doing. contractile elements are responding the change in ca++ concentration. skeletal and cardiac muscle have somewhat different length tension relationships, btw. length tension relationship; see diagram at long sarcomere length, minimal interaction, low tension at favorable length, you maximize interaction and potential force at short length, minimal interaction, low tension in heart muscle the ascending limb is important. length changes the sensitivity of contractile elements to calcium. at ascending limb, ca++ sensitivity is shifted to the right. so at short length you get less force per given [ca++]. length tension stuff is important for heart this is due to some kind of feedback mechanism. cardiac/skeletal comparison (skeletal m, rabbit cardiac, rat cardiac page of handout) the AP is graphed - for skeletal muscle it is very brief, 10 msec. twitch spikes to high peak quickly and relaxes. since AP is so brief, you can fire multiple APs during one brief twitch. when you do that, you get tetany, a fusion of individual contractions into a steady state value that would be the peak of an active state for a single twitch - this generates the active state tension which is higher than twitch tension. rabbit heart: depolarization and repolarization that takes long time, 250 msec. tension development lags, is slower, smaller peak (fewer contractile elements) and takes longer to relax. cardiac muscle can't be tetanized, so hard to prove active state tension higher than resting tension. if you had an arrhythmia producing multiple APs and you tetanized the heart, you'd have no CO. because the AP is so long, the twitch is almost over by the time you finish the refractory period. suppose you had cardiac muscle with short AP? Rat: heart AP very short duration, 40 msec til refractory period over. should be able to generate multiple APs during one twitch. did this to try to tetanize heart. this was done at two temperatures. see diagram in handout (black background). cycling of ca++ from SR seems to take a specific time - eg for ca++ to get back to release site. if you stimulate too soon, you won't release enough ca++ so you can't get fusion. why at 35 degrees is peak force less than at 26? has to do with series elastic element and active state. contractile elements move slower when cold, so more time to move series elastic element and transmit more force. Determinants of arterial blood pressure: look at whole system. what we need to do is maintain arterial BP at optimal level. that's the point. arterial BP = CO * total peripheral Resistance P = F R pressure = flow * resistance HR * SV = CO contractility is determined by sensitivity to calcium and by [ca++] stroke volume is determined by cardiac filling and intrinsic contractility. diastolic filling is determined by blood volume and venous return. HR is influenced by sympathetic and parasympathetic tone. total peripheral resistance is under extrinsic and local vasomotor control Frank/starling curve: see handout. given a particular EDV you get a different stroke volume therefore diff CO etc. Cardiac Cycle: relates several parameters in time. see handout - all plotted on same time axis...two heartbeats. [note: same as last year physio,find diagram] this diagram shows precise relationships between all these mechanical and electrical events. two phases: SYSTOLE and DIASTOLE - defined by early physicians listening to heart. systole: from first to second heart sounds starts at point where left ventricle pressure exceeds atrial pressure, closing AV valve. closing AV valve is coincident with beginning of first heart sound and systole. ventricular pressure increases, intercepts aortic pressure, exceeds aortic pressure, opens aortic valve, and you get ejection of blood into aorta. ventricle relaxes. aortic valve closes when ventric pressure lower than atrial pressure. end systole. note: when aortic valve is closed and av valve is closed, ventricular volume is staying the same. the ventricle is contracting against a fixed volume and is generating an increased pressure. this is the isometric contraction phase or isovolumic contraction phase. as soon as aortic valve opens you get ejection and ventricular volume plummets. you go from end diastolic volume (right before jection) to end systolic volume (after aortic valve closes at end of ejection). the difference between those numbers is SV (stroke volume). notice during relaxation tension drops. isometric relaxation. diastole: from second heart sound to first sound of next beat. as soon as ventricular pressure is below atrial pressure you get rapid filling of ventricle - rapid inflow. during the end of this time you get atrial systole squeezing the last bit of blood into the ventricle. ----break--- [one hour to go. woo hoo!] back to the heart sounds. you have to have ventricular depolarization (QRS) preceding the mechanical contraction. P wave precedes atrial contraction. just realize this. now look at first heart sound. it starts at the beginning of ventric. contraction. this is not what you hear when taking bp. this is what you hear with a stethoscope. they're due to vibrations, not turbulence. the first heart sound is due to the fact that the ventricle has begun to contract and is acting against the AV valve that just closed - in fact, the muscle contracting makes sound. also first sound exceeds period of isovolumetric contraction and enters ejection phase. all of this changing velocity of blood is heard as the lub of the lubDUB. the second sound starts with the closing of the aortic valve. it is NOT due to the valve itself, which makes no noise. it is due to the rebound in aortic pressure due to valve tensing during closure. this is the DUB. the third heart sound is usually not heard; if heard it is due to the blood entering the ventricular changing from rapid filling to slow filling. the change in velocity produces this sound. 4th sound (rarely) heard, eg if atrial hypertrophy - secondary to and coincident with atrial contraction - caused by a large atrium. all the sounds are due to vibrations. the valves do not make noise!! murmurs occur due to turbulence from eg a stenotic valve or prolapsing/incompetent valve or something. in practice, you listen to sounds and hopefully can visualize the cycle since you don't have it in front of you. MECHANICAL ANALOG OF SYSTEMIC CIRCULATION see handout left ventricle is in fact a volume pump, ejects a volume of blood if you don't pump out the right amount, eg, not enough, you have decreased ejection fraction SV/EDV.normally about 60-65%. elastic conduit vessels (eg arteries) are analagous to an air chamber. when you eject the blood during systole , if there were no elastic conduit, you'd have to accelerate all the blood in the whole system. but the aorta et al can accomodate this by expanding. this converts kinetic energy into potential energy. this stretches out bloodflow over longer period of time. potential energy then used during recoil of arteries, promoting further blood flow. the large ladder thing: large cross sectional area of exchange vessels - pressure drops tremendously as resistance increases. and on venous side - analagous to open topped reservoir: volume reservoir only, not pressure. so if heart sides get out of sync, blood can be pooled here. MUSCLE MECHANICS if you just take muscle and let it sit there it generates no tension. this is at rest. now, if you attach it to a weight, but stretch a bit -- isometric contraction generated while tension increases if it doesn't shorten--unless you generate enough force to lift the weight - then you have an isotonic contraction while muscle is actually shortening. then you get isotonic relaxation as it lowers th weight while relaxing, and isometric relaxation finally as tension drops while length remains the same. this is one cycle. the periods are caused isometric contraction, isotonic contraction, isotonic relaxation and isometric relaxation. in muscle mechanics, the passive tension just before you activate the muscle is the PRELOAD. the afterload is the weight of the weight - whatever the muscle has to move when it starts to shorten. [argh. it is only 2:27] so look at heart again. preload: end diastole - post ventricular filling. pressure in ventricle produces tension in the wall (thickness and radius contribute as well) so by analogy, the tension in wall during end diastole, just before ventricular activation, is the PRELOAD (produced by EDP which is produced by EDV based on length/tension curve) afterload: aortic pressure when aortic valve opens. this is why hypertension is not good; increased aortic pressure necessitates increased ventricular pressure which puts additional tension on the muscle wall. Pressure volume relationships: these are analagous to length tension diagrams, but for the whole heart. handout shows schematic of heart during phases of cardiac cycle. pressure volume relationship plots pressure vs volume of heart simultaneously. so we see here a cardiac cycle plotted in time; whereas a p/v chart shows volume on x and pressure on y. [this is mostly repeating what he said before when he went over the cardiac cycle. in fact, it is repeating exacctly what he said before and i'm not typing it again. only difference is the little diagrams of the ventricle sitting there.] next slide shows instant in time pressure v volume instead of cycle across time axis. "ventricular pressure volume relationship" there are limits within which heart can function. what is passive pressure v volume? just keep increasing volume w/o activating it and see what limits are. also, at different volumes, clamp aorta and see what the max systolic pressure for any volume is. this defines the limits of contractility. in cardiac cycle, heart operates within these limits. [well duh.] so we start off at some EDV before activating ventricle. so you have a volume and a passive pressure; preload. you activate ventricle. during isovolumic contraction volume doesn't change. during this time, pressure is increasing w/in ventricle but valves are closed so volume isn't changing. as soon as pressure exceeds aortic pressure valve opens and you get ejection phase. etc etc. the point at which aortic vavle opens is afterload pressure. the way the trajectory moves w/in the extremes determines functioning of the heart . the EDV and ESV define the stroke volume aka the place between EDV and ESV on the x axis. the total area within the pressure volume relationship lines is the total work the heart is doing (eg the integral of this curve). [2:40 and i'm getting anxious] ok, let's look at - he's checking to see if he forgot anything. ok. what happens when you change variables. how does heart perform. that curve defined vntricular function. so, if you increase the EDV (therefore you increase the preload) you increase the amount of work the heart can do, because you increase the stroke volume as shown in the graph in the handout. this also increases the ejection fraction because SV increases MORE than EDV does, percentagewise. if you DEcrease the EDV you are decreasing the preload as well, and you are decreasing the work the heart can do, decreasing the stroke volume. ejection fraction drops too. if you increase the afterload (aka the aortic pressure) the ventricle must generate a higher pressure before the valve opens. so there is less time avail fro ejection phase. so SV decreases, and ESV increases. so ejection fraction decreases. [2:47] if you decrease afterload, more time avail, SV increases, ESV drops. understand these are artificial constructs. clinically more than one variable often changes, there are compensatory mechanisms, etc etc. an additional factor is contractility. no matter what you do you can't increase pressure past the limit of heart's ability. if you increase contractility, though, you shift the maximum pressure curve for a given volume. so you may start w/same EDV and afterload is same, but force generated is greater. so you can more fully empty the ventricle, do more work, eject more blood over same period, ESV drops, SV increases. if a heart were in failure, it has decreased contractility. you get less force generated, less SV, EDV the same, decreased ejection fraction. [woo hoo we're done. tomorrow we'll finish up] --end----