High Yield pt3 PDF

      After depolarization there is transient outward flux of potassium via Ito channels, this transient potassium efflux is phase 1, and is very brief  The potassium efflux brings the membrane voltage down, allowing L-type voltage gated Ca++ channels to open. Calcium influx prolongs the...

      After depolarization there is transient outward flux of potassium via Ito channels, this transient potassium efflux is phase 1, and is very brief  The potassium efflux brings the membrane voltage down, allowing L-type voltage gated Ca++ channels to open. Calcium influx prolongs the repolarization phase and is called the plateau, it is phase 2 High calcium in the cardiomyocyte causes muscle contraction. Phase 2 prolonging the action potential buys time for the Na channels to get out of their refractory period.  Phase 3: Potassium efflux through Ikr and Iks channels, Long QT Syndrome is associated with defective IKR, prolonging depolarization  Phase 4 is at resting membrane potential, Ik1 channels are active making the resting membrane potential for cardiomyocytes -85mV, more negative than pacemakers (-65mV) Cardiomyocyte sodium channels  Sodium channels are inactivated after their phase 0 rapid depolarization, meaning there is an absolute refractory period, and an AP cannot be conducted if stimulus arrives between phase 0 and 2  Calcium influx at the plateau(phase 2) prolongs the AP, makes phase 3 the relative refractory period  If there is a stimulus larger than normal during phase 3, the cardiomyocyte can depolarize, if this happens it is an Early afterdepolarization(EAD) EADs can be a mix of sodium and calcium influx, if it happens closer to the plateau, more Calcium influx because the Na channels are still closed  If a cardiomyocyte is stimulated after repolarization, but before phase 4, this is a delayed afterdepolarization (DAD). DADs can also be caused by either high intracellular sodium or calcium  DADs and EADs lead to arrhythmias Sympathetic (B1) and parasympathetic(M2) increase or decrease the heart rate by altering the slope of phase 4 in the slow response AP Sympathetic stimulation increases activity of funny channels and calcium channels, leads to more cation influx during phase 4 allowing pacemaker to reach threshold sooner Parasympathetic stimulation leads to increased potassium efflux by IKACh channels, and low cAMP production lowers activity of funny channels and calcium channels. Pacemaker will have less cation influx and get to threshold later Causes of arrhythmia  Drugs, ischemia, electrolyte imbalances, alterations in impulse production, damage to the normal conduction pathway, or extra accessory pathways can lead to arrhythmias  Ectopic beats are automaticity of cells outside the normal conduction pathway(example is A fib)  Conduction block is when an area of the normal conduction pathway is unexcitable(examples are AV nodes causing type 1-3 heart blocks, or bundle branch blocks)  Reentry is when an impulse that has either passed through an area of fibrosis, started from an ectopic location, or gone down an accessory pathway reenters the normal pathway. Reentry propagation depends on the refractory time of the normal pathway        5. Myosin walks along actin via the cross bridging cycle 6. Reuptake of Calcium back into the SR by the SERCA pump, minimal Calcium loss by cell via Ca-ATPase or Na-Ca exchanger Frank-Starling Law  Increasing preload increases the force of contraction, thereby increasing stroke volume!  Preload is the amount of blood that fills the heart before it contracts  Stroke volume is the amount of blood the heart ejected during a contraction  As the heart is filled its muscle fibers are stretched giving more cross bridging potential to myosin and actin  Increasing the cross bridging potential increases the force of contraction, to a point  If a sarcomere is stretched too much, the myosin and actin lose their overlap and cannot cross bridge, at this volume force of contraction would be low, stroke volume would be low Alterations in preload can be seen on PV loop Diagrams Afterload: the resistance the ventricle must overcome to eject the blood  High aortic BP, or aortic valve stenosis are examples of high afterload states  High afterload slows the contraction velocity of the ventricles  Slower contraction velocity causes less blood to be ejected during a ventricular contraction, the stroke volume will reduce  Since the stroke volume reduces, more blood remains in the ventricle at the end of systole. High afterload increases the end systolic volume Alterations in afterload on PV Loop Inotropy: The contractility of the heart muscle  Alterations in calcium availability alter inotropy  Drugs like digoxin, and sympathetic stimulation increase inotropy  Increasing the inotropy will increase the stroke volume if preload is constant 22: Cardiac Electromechanical Activity (Benmerzouga)  Cardiomyocyte Excitation-contraction  1. Action potentials travel down t-tubules of cardiomyocytes, inducing confirmation change in L-type calcium channels called dihydropyridine receptors (DHPR)  2. Dihydropyridine receptors on t-tubules are coupled to Ryanodine receptors (RyR) on sarcoplasmic reticulum, Calcium is released from DHPRs and induces the release of calcium from sarcoplasmic reticulum, through RyRs.  3. Calcium binds troponinC, inducing confirmation change in TnT, and TnI, freeing tropomyosin from its attachment to actin  4. As tropomyosin disassociates from actin, myosin binding sites are exposed on actin 23: Determinants of Cardiac Function (Mayrovitz)  Determinants of cardiac function: Preload and Afterload  Preload measures:  End diastolic volume is best measure of preload, how much did the heart fill?  End diastolic pressure, relies on ventricle compliance     Central venous pressure, more CVP leads to more venous return, more preload  Afterload measures:  Wall stress is the best measure of afterload remember the transmural pressure increases the wall tension, in order to contract the cardiomyocyte has to overcome the wall tension  Total peripheral resistance  Aortic/ventricular pressure-easiest to measure CO=SV x HR Determinants  Determinants of Stroke Volume:  Frank starling Law of preload, increased preload increases SV  Sympathetic input increases contractility(Inotropy), increased inotropy increases Stroke volume  Increased afterload increases the resistance the heart is contracting against, slows the contraction and reduces the stroke volume  Determinants of Heart Rate  Increased sympathetic activity activates funny channels and calcium channels, increases the slope of slow wave action potentials, increases the HR  Vagus nerve is parasympathetic. Increased vagus input will reduce cAMP failing to activate the funny current. Also parasympathetic activates IKACh channels, in total it reduces the slope of phase 4, lowering heart rate Peak Isovolumic Pressure(PIP) Lines  This is the pressure developed in the ventricle if the aorta was clamped, it is a measure of contractility  At increasing end diastolic volumes (preloads), the contractility increases because of the stretch of sarcomeres, creating more cross bridging potential.  Increased contractility will be seen as increased left ventricular pressure in this experiment.  If preload increases too much, muscle fibers are stretched too far actin and myosin fail to overlap, this will be seen as lower left ventricular pressure  The steeper the slope of a PIP line, the more contractility  24: Electrocardiography (Mayrovitz)        Is stroke volume changing due to inotropy or preload?  Looking at this graph, the difference in SV between lines at the same preload (vertical difference between dashed line, solid line, and dashed line) is due to inotropy. The dashed line on top has the highest contractility, so it has the highest SV at the same preload  The difference in SV as you move along the same line (the red line) is due to the Frank Starling Law. Increasing preload (end diastolic pressure is a measure of preload) increases SV.      Ventricle Muscle Energy Demand  With higher afterload, there is more resistance for the ventricular myocardium to contract against.  A harder working muscle needs more O2  Measures of ventricle energy demand include:  Area under the Pressure vs Time curve  Tension time Integral  Double Product: MAP x HR Blood flow to the heart Myocardium gets its blood flow during diastole, when the muscle is relaxed and vessels are not compressed  Wall stress is greatest on the luminal side of the wall, and because the endocardium is the last to relax, it has the most compromised blood flow  The endocardium is the most vulnerable portion of the wall to ischemia Respiration on SV and BP  As we inhale, intrathoracic pressure reduces to let air flow in, when intrathoracic pressure reduces, transmural pressure of vessels increases (transmural pressure is Inside-outside).  Higher transmural pressure will increase wall stress, increasing afterload, and contributing to reduced stroke volume when we inhale. The interventricular septum is also pulled left by reduced thoracic pressure, reducing preload to reduce SV.  If the systolic blood pressure drops more than 12mmHg due to inhalation, that is pulsus paradoxus  Inhalation decreases the stroke volume, but increases the venous return. Increased VR and increased ESV will increase preload, frank starling mechanism will increase the SV on the next contraction  An EKG represents moving waves of changing electrical activity within the heart The first positive wave is depolarization of the atria (p wave) The second is a series that represents depolarization of the ventricles (QRS complex) The final positive wave represents repolarization of the ventricles (T wave) A moving dipole causes a voltage change at a distance  A dipole is a moving wave where one end is positively charged and the other end is negatively charged  As the dipole (depolarization wave) moves it produces a change in voltage on the electrodes on the surface (skin) and that is what represents the positive and negative deflections of an EKG  When the dipole is exactly perpendicular to the electrode on the skin the voltage is zero There are 4 limb leads placed on the patient and 6 precordial leads  1 limb lead goes on each extremity  The right leg is the ground reference  The other limb leads standardize the direction (positive or negative)  They create a triangle on the body called Einthoven’s Triangle  The average wave should be moving toward the PMI of the heart (down and to the left)  If the dipole is moving toward the electrode (positive) it will be a positive deflection on the EKG  If the dipole is moving away from the electrode (negative) it will be a negative deflection on the EKG The mean electrical axis is the average direction the wave of depolarization is moving during the QRS complex  R wave is the big positive deflection  S wave is the negative deflection that follows R  Q is a negative deflection that can precede R Precordial Leads are labeled V1-V6 and go across the chest  The location on the chest determines which part of the heart they are looking at  V1-V2 look at Right ventricle  V3-V4 look at the septum  V5-V6 look at the left ventricle Ventricular depolarization happens Endo to Epi and ventricular repolarization happens Epi to Endo The reason some leads (ex: V1) look upside has to do with the direction of the depolarizing wave  Since V1 is looking at the right ventricle it has a very small R wave because the majority of the electrical impulse for the ventricles are moving toward the left ventricle and mostly AWAY from V1 (although there are still some moving toward V1 making it a positive deflection just very small one)  V6 has the largest R wave because it looks at the left ventricle where the majority of the impulse is traveling TOWARD V6 during ventricular depolarization    This information is extremely important in localizing pathology during MIs or other cardiac events! Mean Electrical Axis (MEA)  The MEA is determined by adding all the vectors together from each stage of the cardiac cycle resulting in the average direction of the depolarizing wave  Finding MEA a step by step approach:  Determine which lead is most isoelectric (which one looks like the straightest line with the smallest positive and negative deflections  Looking at the circle graph, find which lead is perpendicular to the lead that is most isoelectric  Look at the EKG and see if that lead is more positive or more negative  If it's more positive the MEA is its positive direction on the circle graph  OR if only 2 leads are given, use the thumbs up approach  If your left thumb is lead 1 and your right thumb is lead 2  Thumbs up means the lead is more positive and thumbs down means the lead is more negative  If BOTH thumbs are up its a normal axis  If the LEFT thumb is up and the right is down then it is a LEFT axis deviation  If the RIGHT thumb is up and the left thumb is down then it is a RIGHT axis deviation EKG Patterns  Conduction Blocks  If the PR interval is lengthened compared to normal but it is the same length all along then you have a first degree block  If the PR interval that is lengthened but is progressively getting longer each times until you miss a QRS complex all together then it is a second degree block  Also sometimes called Mobitz 1 or Wenkebach  The PR interval is the same length all along but you intermittently lose a QRS complex  Conduction blocks can cause axis deviations  MEA shifts TOWARDS hypertrophied muscle and bundle branch blocks and AWAY from infarcted muscle  Ex : Right bundle branch block can cause a right axis deviation  Ex: Left bundle branch block can cause left axis deviation  Ectopic Foci  If you have an impulse that arises on its own outside of the SA node or outside of the proper timing  it is called an ectopic foci  Too early impulse -----> Premature atrial complex (can be positive or negative)  In ventricle -----> Premature ventricular complex or ventricular tachycardia  Multiple in ventricle ----> ventricular fibrillation  In atria ---> Supraventricular tachycardia  In atria without going to ventricle ----> Flutter  Multiple in atria ---> Atrial fibrillation  Decreasing afterload  Remember afterload is the pressure the heart needs to overcome to eject blood  MAP is a good estimate of afterload  The end systolic volume decreases along the PIP line  The SV (width) increases  The preload is unchanged  Change in contractility  Contractility is the slope of the PIP line  As you change contractility the slope of the line changes  This increases or decreases ESV  The SV is increased or decreased as well  With a decrease in contractility eventually the heart must compensate  It does this by increasing preload  This increases SV  If you add an inotropic agent it will increase contractility, reducing the preload and SV 25: Cardiac Cycle-Pressure Volume Loops (Mayrovitz)   Cardiac Cycle  Inlet valves (mitral and tricuspid) open and the heart is filling (S3)  Atrial kick/systole ----> p wave and S4 heart sound  Mitral and tricuspid valves close ----> Isovolumetric contraction  Aortic and pulmonary valves open (S1)-----> ejection (EF = SV/EDV)  Valves close (S2)----> isovolumetric relaxation  Left ventricular pressure and aortic blood pressure are the same at 2 points: Start of ejection and the point of pressure gradient reversal  Aortic blood flow continues for a bit despite the reversal in pressure PV Loops  The loop is created by two lines, a line representing contracting of the heart and one representing filling of the heart  The slope of the PIP line represents contractility  Systolic BP is the top of the loop  SV is the width of the loop  Diastolic BP is the point at which ejection begins  The inlet valves (mitral and tricuspid are always closed during isovolumetric states  This is what allows the heart to have NO change in volume during those times 26: Cardiac Cycle-Wiggers Diagram (Mayrovitz)  Wigger’s Diagram Review  As pressure rises in the left ventricle, the mitral valve closes and the increase in pressure opens the aortic valve causing ejection and a drop in left ventricular volume  Once the aortic valve closes there is a moment of isovolumetric relaxation and then the mitral valve reopens and left ventricular volume rises and aortic pressure falls  Then the cycle repeats itself 27: Pump Failure and Hemodynamics (Mayrovitz)     Heart Sounds  Sounds are due to vibrations of the vessel walls and the blood moving  High BP tends to cause more and louder sounds due to the higher rate of valve closure  S1 = inlet valves closing  Onset of ventricular systole  QRS complex  Onset of isovolumetric contraction of PV loop (D)  S2 = outlet valves closing  Ventricular relaxation  End of T wave  Beginning of isovolumetric relaxation on PV loop (C)  S3 = Early Diastole  Rapid filling  Heard in a volume overloaded state or in high atrial pressure  In between T wave and following p wave  During early filling on PV loop (3)  S4 = Atrial systole  Atrial contraction  Head in LVH or RVH or in a stiff ventricle state  During p wave  End of filling on PV loop (4) Murmurs and Pulses  Murmurs = sound produced by turbulent flow  Only when critical Reynolds number is exceeded  Scenarios = stenosis, high cardiac output, high regional flow  Carotid and jugular Pulses  Carotid graph  The red circle indicates the delay between ventricular ejection and the pulse wave arriving in the vessel  Jugular graph  Point a = atrial contraction  Point c = isovolumetric contraction  Point x = atrial relaxation as ventricle contracts  Point v = atrial filling Pump failure  Heart failure is a condition where the cardiac output cannot meet the metabolic demands of the peripheral tissues. This can be a result of systolic failure, or diastolic failure  A systolic failure is an inadequate myocardial contraction, the heart cannot pump blood out.  Death of a portion of myocardium due to MI will render it unable to contract, can lead to systolic failure.  A diastolic failure is a filling defect, the heart does not receive adequate preload. Concentric hypertrophy (hypertrophic cardiomyopathy) thickens and stiffens the ventricle wall, making it less compliant, as it fills it will increase in pressure quicker closing the mitral valve before adequate preload enters.  Volume overload is going to be a major symptom of heart failure, there is fluid buildup and backflow in the part of the body behind the failed pump(Right heart: leg swelling, ascites, left heart: pulmonary edema) Pump failure: SV reduces in both!  Systolic  Stroke volume reduces due to a lack of contractility  End Systolic Volume increases, preload will add to increased ESV, increasing EDV  Diastolic  Stroke volume reduces due to lack of preload, contractility is maintained  End Diastolic Pressure increases  Summary of Systolic and diastolic failure  Aortic Stenosis: systolic murmur  Stiffening of the aortic valve leads to increased valve resistance, it is an example of increased afterload  Increased afterload requires larger left ventricular pressure for ejection to occur, this will be seen as a longer isovolumetric contraction on the PV loop, and a increased gradient between LVP and ABP on Wiggers diagrams Aortic Regurgitation: diastolic murmur  A leaky aortic valve that does not completely close after ventricular contraction  Blood that was ejected into aorta will flow back into the left ventricle because of the leaky valve  The loss of blood volume in the aorta will be seen as a rapid drop in aortic blood pressure on a Wiggers diagram. On the PV loop, volume will increase during the isovolumic contraction and relaxation phases Mitral Stenosis: Diastolic murmur  