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Quiz 3 Practice Questions 1. For each of the following ionic species indicate (a) the direction of their chemical gradient and (b) the direction of their electrical gradient for normal resting myocardium: The chemical gradient is simply determined by concentration. Extracellular concentrations in excess of intracellular concentrations drive the ion into the cell. The current membrane potential and the charge on the ion determine the electrical gradient. Normal resting myocardium has a negative membrane potential, and thus positive charges experience an inwardly directed electrical gradient (opposite for negative charges). i. ii. iii. Sodium i. Chemical Gradient: Inward ii. Electrical Gradient: Inward Potassium i. Chemical Gradient: Outward ii. Electrical Gradient: Inward Calcium i. Chemical Gradient: Inward ii. Electrical Gradient: Inward 2. Use the Nernst equation to calculate the calcium equilibrium potential if the extracellular concentration is 1mM and the intracellular concentration is .0001 mM. [πͺπ+π ]π βππ. πππ½ πππ ( ) [πͺπ+π ]π π βππ. πππ½ ππβπ ππ΄ π½π¬π = πππ ( ) π πππ΄ βππ. πππ½ π½π¬π = β βπ = πππ ππ½ π π½π¬π = 3. What causes refractoriness in myocardium? What is the difference between the βeffectiveβ and βrelativeβ refractory periods? Refractoriness is the inability to fire off an action potential for a short duration following activation. This phenomenon is primarily caused by channel inactivation, which blocks ion current generation upon subsequent depolarization. In fast-response cells (like ventricular myocardium) during the effective refractory period, all the Na channels have been inactivated, and thus any stimulus will fail to evoke another action potential. However, after some short time has passed, enough Na channels may return to the deactivated/unactivated state such that a larger than normal stimulus may be sufficient to cause a myocardial cell to fire off. This period during which the myocardium is responsive ONLY to larger than normal stimuli is termed the relative refractory period. 4. For each of the following parts of a ventricular action potential, identify the predominant ionic currents at work: To be technically accurate, there are generally multiple currents at work during each phase of the myocardial action potential, and some are also subdivided such that there are many types of Ca or K currents. In its most simple form, however, we can generally say the following i. ii. iii. iv. v. Phase 0 i. Fast Na current (directed inward) Phase 1 i. Transient outward K current Phase 2 i. L-type Calcium current (directed inward) Phase 3 i. Delayed rectifier K current (directed outward) Phase 4 i. IK1, the inwardly rectifying K current (directed outward) 5. Explain what is meant by βinward rectifyingβ in regards to the potassium IK1 current. βInwardly rectifyingβ is a term descriptive of channel conductance, not the current direction! An inwardly rectifying channel is one that reduces its conductance under conditions that would otherwise further promote current development. When talking about the potassium current, this means that the channel conductance decreases as the membrane potential becomes positive because a positive membrane potential would promote K efflux. Conversely, the conductance of the inwardly rectifying K channel increases as the membrane potential becomes sufficiently negative, and this change partly accounts for the bend in the AP waveform during phase 3 6. What features determine action potential conduction velocity in myocardium? How does this differ in ventricular and nodal myocardial cells? Action potential conduction velocity is determined by two factors, the total amplitude of the AP upstroke (phase 0 amplitude) and the rate of change of the membrane potential during the upstroke (phase 0 slope). The AP amplitude serves as the driving force for local cellular currents, whereas the slope describes the rapidity by which adjacent portions of the membrane can be depolarized (given a sufficient potential amplitude). The difference between ventricular and nodal myocardial cells is the source of the phase 0 upstroke. In ventricular myocardial cells, also known as βfast response cellsβ, Na channels open quickly, producing a very sharp and large AP spike. Nodal cells, however, utilize Calcium channels, which produce more of a gradual depolarization by comparison. Thus, AP conduction through nodal cells tends to be slower, as dV/dT in these cells are reduced (an incredibly important feature). 7. Match the ECG interval/wave on the left with the appropriate associated term on the right: Terms on the right have been rearranged i. ii. iii. iv. v. vi. PR QRS ST QT RR T AV conduction Ventricular Contraction Normally isoelectric Duration of ventricular AP Determinant of Heart Rate Ventricular Repolarization 8. How do you identify (roughly) a normal sinus rhythm? AV block? Bundle Branch Block? A normal sinus rhythm typically has the following features: ο§ Upright P wave in lead 2 (lead numbers arenβt a priority here. I wonβt ask you to interpret other leads) ο§ Every P wave is followed by a QRS complex ο§ PR interval is about .2 seconds or shorter ο§ Heart rate is between 60-100 bpm ο§ QRS interval is < .12 seconds (it is not imperative you know this number, just recognize that a normal QRS occurs very quickly and has a sharp, compact, spikey appearance) ο§ Concordant T wave (T wave has same sign as QRS deflection) ο§ R wave progression (you donβt need to know this, but Iβm including it here) Understanding what makes a normal sinus rhythm is key to identifying abnormalities such as: Tachycardia β Heart rate > 100 bpm Bradycardia β Heart rate < 60 bpm AV block β abnormal conduction through AV node leads to 1 of 3 effects 1st degree: sustained PR interval > .2s 2nd degree: Two subtypes Type 1: PR interval lengthens from beat to beat until the AV node fails to conduct (missed QRS complex), and the cycle repeats Type 2: PR interval is constant, but occasionally the AV node fails to conduct rd 3 degree: Complete conduction block. P waves and QRS complexes occur independently Bundle Branch Block: Hallmark is a widened/abnormal QRS, but the overall pattern seen depends on whether the block occurs in the right or left bundle branch. T-wave concordance can also go out the window. 9. In lead 2 of an electrocardiogram (see fig 3-7), what generates the large positive deflection in the QRS complex (also known as the R wave)? When might you see a large negative deflection instead (S wave)? It is important to remember that in an ECG, you are measuring body surface potentials. These potentials are reflective of two things, the first and most obvious being myocardial membrane potentials. The second, and perhaps slightly less obvious factor though, is tissue mass. The right and left ventricles contract at slightly different times, yet their potentials still overlap significantly. However, the pressures required by the systemic circulatory system are far in excess of that found in the pulmonary system. As a result, the left ventricular βfree-wallβ mass (the wall opposite the septum) is significantly greater than in the right ventricle. Hence, during ventricular contraction, potentials generated by left ventricular free-wall depolarization overwhelm those of the right ventricle. Hence, the large spikey deflection during the QRS complex is a result of left-ventricular depolarization! Why do you see an upright deflection in lead 2 (R wave)? Lead 2 is commonly used because its orientation is along the predominant conducting axis of the heart, and it points from the atria toward the left ventricle. If instead you were looking in a different direction, away from the left ventricle, you would see a negative deflection (S wave). 10. Explain the concept of overdrive suppression Fromhttp://www.cvphysiology.com/Arrhythmias/A018.htm Although the primary pacemaker site within the heart is the SA node, other cells have pacemaker activity (automaticity) or have the capacity of becoming pacemakers. These can be normal cells such as those located in the AV node and purkinje fibers, or they can be other cells that display automaticity because hypoxic conditions have triggered pacemaker currents. The SA node is normally the dominant, driving pacemaker because it has the highest intrinsic rate of spontaneous automaticity. For example, pacemaker sites within the ventricles typically have a rate of 30-40 depolarizations per minute, whereas cells within the AV node and bundle of His have an intrinsic rate of 40-50 depolarizations per minute. In contrast, the normal resting sinus rate is 60-100 depolarizations per minute, although it can be much higher under conditions of sympathetic activation. The higher frequency of SA nodal firing suppresses other pacemaker sites by a mechanism called overdrive suppression. If a latent pacemaker is being depolarized at a higher frequency than its intrinsic rate of automaticity by an adjacent cell that is driven by the primary pacemaker, then the increased frequency of depolarizations leads to an increase in intracellular sodium ions because more sodium ions enter the cell per unit time. This increased sodium stimulates the Na+-K+-ATPase (increases its activity) to expel more sodium from the cell in exchange for potassium (see figure). Because this pump is electrogenic, increased pump activity increases the amount of hyperpolarizing currents generated by the pump. This drives the membrane potential more negative, thereby offsetting the depolarizing pacemaker currents (If) being carried into the cell. This effectively prevents the pacemaker currents from depolarizing the cell to its threshold potential, and thereby prevents the spontaneous generation of action potentials. If the cell ceases to be driven by the SA node (e.g., because of AV block), then the additional hyperpolarizing currents will be lost and spontaneous depolarization and action potential generation can occur. 11. What features promote re-entrant tachycardia? From lecture, the features that promote re-entry are: 1. Unidirectional block 2. Dispersion of refractoriness 3. Slowed conduction (gives excited tissue more time to recover) 4. Shortened recovery time 12. Define the following phrases: i. ii. iii. iv. v. vi. sinus bradycardia sinus tachycardia atrial tachycardia atrial fibrillation ventricular tachycardia ventricular fibrillation Heart rhythms tend to be named using a two-word convention. The first word describes the location of action potential origin (the effective pacemaker) or site of re-entry, and the second describes the contraction. Sinus = originating from the SA node Atrial = originating in the atria Ventricular = originating in the ventricles Bradycardia = slowed, but coordinated contraction (<60bpm) Tachycardia = fast, but coordinated contraction (> 100 bpm) Fibrillation = rapid, but completely uncoordinated contraction