Week 1 Flashcards
Two components of the heart
electrical and mechanical
Cells in electrical portion and difference in response to action potential
- nodal cell: slow - myocyte: fast
Why would fibrosis slow down conduction
interrupts gap junctions which are needed/responsible for conduction of ions from one cell to the next.
Where does automaticity start?
SA node
Electrical pathway in the heart
SA node–> atria–> AV node–> Bundle of His–> Purkinje Fibers–> Ventricles
What happens when a cell depolarizes?
inside of the cell becomes more positive
How does the electrical response travel from cell to cell?
positive charge comes into the cell then flows through the gap junction to depolarize the neighboring cell
Why is size important for conduction
larger the diameter of the cell, the greater the conduction
Importance of difference in size between the SA and AV node
- SA node has large and fast fibers compared to the AV node which has small and slow fibers which allows time for blood from atrial contraction to fill the ventricles. - Also, allows for separation of atrial contraction from ventricular contraction
Action potential in Purkinje fibers
fast action potentials that depolarize ventricular cells almost spontaneously to achieve one fluid beat of the ventricles.
what differentiates slow and fast action potentials? - values?
- resting membrane potentials - Fast action potentials go down to a lower, more negative resting membrane potential (-85) and includes Purkinje fibers and cardiac myocytes. - Slower acting potentials include nodal cells and are at (-65)
What establishes the resting membrane potential? What amount of it is inside the cell?
- K+ - high concentrations
How does depolarization occur?
- Na+ and Ca++ are in greater concentration outside the cell. When they enter the cell, they make it more positive causing depolarization
How to repolarize the cell?
- Na+/K+ ATPase helps get the Na+ out of the cell - K+ channels also allow for K+ to move out of cell and make it more negative - During hyper-polarization (more negative than usual resting potential) Na+/K+ ATPase will pump K+ in to get back to resting membrane potential
Slow-Response Action Potential
- Phase 4 (funny current=slow depolarization): HCN channel is open during this phase allowing for influx of Na+, Ca++, and K+ and as resting membrane changes the closer it gets the threshold, the less permeable it is to K+ - Phase 0 (depolarization): Ca++ channels open up, allowing for influx of Ca++ through L-type channels - Phase 3 (repolarization): Ca++ channels close and K+ channels open, K+ leaves the cell allowing it to repolarize
How do the ions get in and out of the cell?
- Through ion gates
How do we have fast and slow depolarization?
- We have activation and inactivation gates in the channel and fast cells have faster reacting gates making them depolarize and repolarize faster
Fast-Response Action Potential Phases
- Phase 0 (rapid depolarization): Influx of Na+ into the cell - Phase 1 (initial repolarization): K+ channel opens and K+ leaves the cell and Na+ innactivation gates close so Na+ influx stops - Phase 2: Ca++ comes in through L-type channels but results in plateau due to K+ going out of cell through K channels - Phase 3: More K+ channels open and efflux out of the cell which then causes impermeability to Ca++ so now CA isn’t coming into the cell - Phase 4: Voltage-gated K+ channels close but K+ leak channels are still open, allowing for a return to resting membrane potential
Sympathetic regulation of electrical current of heart - what is being released and what is it binding to?
- post ganglionic adrenergic nerve terminals release norepinephrine, epinephrine, and dopamine which bind adrenergic receptors such as α, β1, and β2 that are coupled to the heteromeric G proteins
receptors coupled to the heteromeric G proteins
- α is located in arteries - β1 is located in the heart - β2 is located in the lungs
Pathway of Sympathetic regulation of electrical current of heart myocytes
- Myocyte: NE binds the β1 on the myocyte–> GDP is exchanged for GTP–> heteromeric G protein dissociates–> Gαs stimulated AC–> increases cAMP–> Activated PKA–> Phosphorylates L-type Ca++ channel, SR, and ryanodine 2 receptor (RyR2)–> increases Ca++ influx into the cytosol as well as increases Ca++ storage in the SR–> Increases heart rate
What does sympathetic innervation do to heart rate for myocytes? Why?
- Increases heart rate - Refractory period is shortened and repolarization can happen quicker because there is a large increase in intracellular Ca++ as well as Ca++ stores which will increase the permeability of K+ so it will efflux out of the cell to help balance the positive intracellular charge caused by the high [Ca++].
Pathway of Sympathetic regulation of electrical current of heart noda cells
- Dopamine (DA) binds β1–> Gαs is activated –> acts on “effectors”–> modulate signaling at HCN funny current and L-type channels–> Increases heart rate
What does sympathetic do to nodal cells and what does it do heart rate? - what happens to phase 4?
Increases heart rate because it is opening channels faster and allowing for faster influx of ions which allows for an increase in action potential frequency and allows for threshold to be lowered -Phase 4 of depolarization becomes steeper
Beta blocker - effect on myocyte - effect on nodal cell - what is affected?
- Myocyte: Drug binds β1 G protein-coupled receptor–> prevents endogenous agonists from being able to activate the receptor–> prevents conformational change of heteromeric G protein–> G protein is inactivated–> no signal transduction–> decreased ability to bring in Ca++–> increased concentration of intracellular K+–> causes hyperpolarization–> decreased contraction (decreases ionotropy) - Nodal Cell: Drug binds β1 G protein-coupled receptor–> prevents endogenous agonists from being able to activate the receptor–> prevents conformational change of heteromeric G protein–> effectors are inactivated decreases heart rate (chonoropy)
What other channels do beta blockers have affinity on?
Na+ channels
How does parasympathetic effect nodal cells?
- vagus nerve releases ACh –> binds muscarinic ACh receptors –> Activates Gai complex –> causes decrease in cAMP and other effectors are also being elicited to increase K+ in the cell which increases threshold??
Parasympathetic muscarinic receptors
- M1 is located in the CNS with some peripheral system components too. So think exocrine, sweating. - M2 is located in the heart Specifically for muscarinic signaling and are only expressed in nodal cells. - M3 is located in the lungs
Atropine - what does it do? - effect?
- signature drug that binds these M2 receptors for blockade - No signal transduction means no decrease in heart rate, so it’s going to increase your heart rate
Classes of anti-arrhythmic agents
- Class I: Na+ channel blockers - Class II: Beta blockers - Class III: K+ channel blockers - Class IV: Ca+ channel blockers
Class III - what do they do? - ex? - underlying mech - what happens to conduction velocity
- K+ blocker - amniodarone - If you’re blocking the K+ channel, then repolarization is going to take that much longer to occur, and you see a rightward shift in Phase 3 of the AP. - It slows down
Class I - 3 subclasses
- Ia: moderate Na channel block; slightly more pronounced Phase 0 and prolonged repolarization - Ib: mild Na channel block; shorten AP duration and refractory period - Ic: marked Na channel block; increased slope of phase 0 but no prolonged repolarization
Class IV - what is it? - what happens to action potential? - which channel does it bind to?
- Calcium Channel Blockers - Slow rise in AP (Phase 0) and prolonged repolarization (Phase 3) at AV node - L-type channels
Class II - what is it? - what does it do to AP? - how often is it used?
- beta blocker - Prolongation of phase 4
How are beta blockers and calcium channel blockers similar and different?
- Calcium channel blockers is direct but only affects one portion of calcium movement while Beta-blocker blocks every aspect of calcium movement while doing it indirectly as well as HCN channels in nodal cells - main antiarrhythmic class used across the board
Digoxin - MOA - What would happen to the resting membrane potential? - What happens to the AP
- blocks the Na+/K+ ATPase leading to Na+ not being able to leave the cell. This indirectly blocks Na+/Ca2+ exchange, leading to increased Ca2+ inside of the cell - It would increase (become less negative) because you block the Na+/K+ ATPase, and by doing that, you now increase intracellular Ca2+ level (positive ion), so you’re resting membrane potential becomes less negative.
Adenosine - MOA - used for? - effect?
- binds adenosine receptors which will stop heterotrimeric g proteins from being activated so it inhibits the influx of Ca2+ through the funny channels and the L-type Ca2+ channels through its cAMP signaling and increases K+ efflux with the βγ segment - supraventricular tachycardia (SVT) - Adenosine decreases conduction; is like having a sudden heart attack- it completely stops everything.
What happens if SA node isnt working
Other cells also have automaticity and will take over.
Overdrive suppression - what is it? - what regulates it??
- if you have SA node firing it is going to suppress the automaticity of the subsequent pacemaker cells beneath it so you wont have separate pacemakers firing at the same time - Na+/K+ ATPase
what is the Na+/K+ ATPase? - what does it cause?
- out: Na+; In: K+ - Hyperpolarizing gradient
What happens if you increase SA node activity? - What can do this?
- Increase heart rate - Sympathetic innervation
What happens to Na+/K+ ATPase with increase in heart rate?
Na+/K+ ATPase works faster which pumps more and more Na out of the cell causing it to become hyperpolarized and making the adjacent cells hyperpolarize even faster so their resting membrane potentials will be a tad bit even more negative so they will not spontaneously depolarize before the SA node because it makes their resting membrane potential a tad bit lower (more negative) than that of the SA node
How do you get automaticity somewhere else in the heart
- Pacemaker cells outside of SA node become quicker than the SA node and they start to set the heart rate
Why do you have slow gradual depolarization in phase 4 of nodal cells?
give your cells time to close that inactivation gate before starting another depolarization
Gates of Na channel - which is which - how do they work?
- Inside: Inactivation - Outside: Activation - During phase 1 after upshoot and as you begin to get to plateau the inactivation gate closes By the time you get to phase 3 the gates have been reset so the inactivation gate is open again but activation gate is closed
What happens when you have Hyperkalemia? - Na channel - Ca channel?
when there is high levels of K+ on the outside of the cell it will decrease the efflux of K+ out of the cell making the inside of the cell more positive. Since the cell is more positive the resting membrane potential closer to the voltage level of where the Na gates close so the inactivation gates close. - normal
what will the action potential resemble with hyperkalemia? - how?
- fast action potentials will now resemble a nodal cell (slow) since the inactivation gate of the Na+ channel are closed meaning that the fast acting Na channels are not working - Nodal cells actually have the same fast acting Na channels as the myocytes they just do not work because their resting membrane does not get negative enough. With hyperkalemia since you change the membrane potentials of the fast acting cells (myocytes) to be more positive they now act more like the nodal cells and become slow.
What happens to Ca if you continue to increase levels of potassium?? - why is this important?
- Ca channel will also become inactivated - without Na and Ca coming into the cell you cannot have an action potential meaning that the cell cannot be excited
what happens when you have increased physiologic stimulus at the SA node (sympathetic innervation)? - how?
- Increases the action potential. - Nor-epi will bind to G alpha S –> increase adenylyl cyclase –> increase in cAMP –> increase in PKA –> increase in intracellular Ca c
if you want your action potential to increase and you’re in the slow action potential cells what do you do to phase 4? - What would happen the ECG
- Make it more steep so it hits threshold quicker and you lower threshold potential so you get quicker action potential frequency which increases conduction at the SA node - space between two R’s would be smaller
How can you slow down the SA node physiologically? - What would happen to phase 4? - What would it look like on ECG?
- increase vagal tone, which decreases frequency - Not as steep, making it a little slower so it reaches threshold slower and makes the threshold potential higher so action potential frequency slows - space between two R’s would be larger (longer)
what happens if you are on beta blocker or vagal tone is increased? - Where will automoticity start to go?
- SA node will slow down. - AV node
if you only have stimulus at AV node (SA node no longer firing) what will ECG look like
Absence of P wave but would have QRS complex and T wave
How to Calculate the rate
• Using the hashmarks we can see that there are 3 of the taller hashmarks and since the space between two tall hashmarks equals 2 seconds we know that this ECG reading is only for 6 seconds. We then count how many R peaks are located within those 3 tall hashmarks (6 seconds) which in this case is 5. We then multiply the amount out R complexes in between the hashmarks (5) by however long it would take to get to 60 seconds (in this case it is 10). So this patient would have a rate of 50 BPM.
What is an escape beat?
- It is the wide QRS complex and it is because you do not have over draft suppression and there is no p wave.
How do you know when an escape beat start at AV node vs when it start after?
- If there is no P wave but the QRS complex is normal in width ( 2.5 small boxes) then is is at AV node - if QRS complex is really wide it means it is after the AV node
Ventricular escape beat
- escape beat that occurred after AV node
Junctional escape beat
- escape beat that occurred in AV node
What is wrong? - what would normal look like?? - mechanism for this problem?
- Prolonged PR interval - 3-5 small boxes - AV conduction block
What are the ways you can get a conduction block?
- Ischemia, Scar formation, Fibrosis - Cell in absolute refractory period
Functional ways to get a conduction block?
- physiological (catecholamine release), - pharmacological (pro or antiarrhythmic or other medications that can cause arrhythmias), - pathological stimulation - barrier (scarring or fibrosis)
- What is happening? - what does this tell us? - causes? - name dysfunction
- PR interval keeps getting longer and longer - tell us that there is gradual increasing blockage (at some point you actually block conduction from SA to AV so you don’t get conduction of the ventricles) - ould either be that there was scarring or fibrosis (fixed) or it could be that it was functional and that whatever it tried to hit was in refractory mode and was just unexcitable - Wenckebach (preferred name: 2nd degree Mobitz type 1)
What does PR interval tell you?
Conduction from SA to AV (atria to ventricle)
- Is the rhythm regular or irregular? - how do you know? - formation of P waves - identify what this rhythm
- irregular - Not every P wave has a QRS and the R-R intervals are not the same all the way across - saw toothed pattern - atrial flutter
What would happen if we had a QRS after every single P wave in a saw tooth pattern?
- tachycardia and it would be termed: Rapid ventricular response (if every time we were getting those very fast P waves it was conducting all the way down to the ventricles)
Cause of atrial flutter
etting spontaneous premature atrial beats and these are causing reentry circuits in the atria and bc the AV node is still in refractory you’re not getting full propagation down but you still keep circulating these reentry patterns and so they just keep forming that particular beat. So you keep getting that spontaneous depolarization of the atria
What does the fact that the P waves look like each other mean??
It is taking the same circuit every time
A fib vs A flutter?
- In a fib that are not any P and the QRS complexes are spread out unevenly.
Unidirectional block - how it interacts with the side that is blocked
- The impulse will be blocked on one side and so will go down the unblocked pathway like normal. Once the unblocked pathway has made it all the way to the bottom the impulse can travel into the blocked pathway from below in a retrograde fashion as long as those cells work.
How is a re-entrant loop formed in a unidirectional block
- normally the impulse traveling retrograde will re-enter the pathway that works correctly before it has had a chance to repolarize making the impulse stop. - However, if the impulse traveling retrograde is slow enough it will get back to the unblocked portion once it has already repolarized and then makes it depolarize again.
Define - Absolute refractory period - Effective refractory period: - Relative refactory period: - Supranormal period:
- ARP: Np depolarization - ERP: non-propogated depolarization (some od the cells are repolarized but not enough for the impulse to actually propogate - RRP: depolarization but only with strong stimulus - Supranormal: Depolarization with weak stimulus
In order to get an early after depolarization, what has to happen to the inside of the cell? - phase 2 vs 3
- membrane potential has to increase so one of the ions has to increase to make the cell more positive and the specific ion will depend on what phase the cell is in - Phase 2: Ca because the Na gates have just closed so no excess Na can get into the cell - Phase 3: Na or K. The Na channels have closed and have started to recover so they can be re-activated. Also, could be K refusing to leave the cell because there is a lot of K on the outside of the cell.
How do you get delayed after depolarization - what could cause this?
- The cell fully repolarizes and then it gets another signal - This is immediately after repolarization, its not in the refractory period and you’re getting another depolarization and if it reaches threshold then you’ll get another AP - Accumulation of Ca2+ intracellularly which can be caused by drugs
Branching mechanisms of arrythmias
Altered Impulse Conduction and Altered Impulse Formation
What is altered impulse formation, what are we thinking about?
Altered Automaticity, Triggered Activity (Early After Depolarization, Delayed After Depolarization)
What is Altered Impulse Conduction
Conduction Blocks + Re-entry
What could be happening with an MI?
Abnormal Automaticity
How do you classify arrythmias?
Tachycardia vs bradycardia
Brady cardia arrythmias - SA - AV - Ventricular
- SA Node = Sinus Bradycardia, Sick Sinus Syndrome - AV Node = Conduction Blocks, AV Node Junctional Rhythm - Ventricular = Ventricular Escape Rhythm
Tachy cardia arrythmias - SA node - AV node - Ventricular
- SA Node = Sinus Tachy - AV Node = A. fib, A. flutter, Premature beats, SVT, Re-entry - Ventricular = V Tach, V fib, Premature beats, Torsades de Pointes
Steps of EKG interpretation
- Rhythm 2. Rate 3. Axis 4: Intervals (PR, RR< QT)/ Segments (PR, ST) 5. Complexes (QRS)/ Waves (P,T)
How do you figure out if the rhythm isn’t normal?
R-R interval isn’t constant
Polymorphic p waves
- p waves is present but in a bunch of little p waves
Do different peak heights matter?
- as long as its not very big then it is most likely slight voltage variation that is not of concern
A fib - findings - altered impulse or conduction - one location or multiple? why?
- Irregularly Irregular, Lack of P-waves (the P-waves look like they are “fibrillating”) — & that the QRS complexes are irregular from one to the next - conduction - multiple, wandering re-entry
What is Rapid Ventricular Response?
- Heart rate has hit triple digits
Treatment of Afib
- Rhythm control: Beta-blockers OR Ca+ channel blockers - Rate conrol: cardioversion - antithrombotic agents– bridge therapy with low molecular heparin bc it is fast acting and then warfarin as chronic blood thinner
Non dihydropyridine meds - importance?
- diltiazem & verapamil - these are just for heart and not vascular system
Importance of adrenergic antagonists as tx for Afib
- Slow down conduction rate through the AV Node which slows down response of the ventricle - Because we antagonizing the SNS which stimulates that’s going to slow the rate of depolarization in the SA node; So it kind of has dual function in both
Importance of Antithrombotic Agents
- B/c of the irregular blood flow in the heart you are going to have increase risk of clot formation & the clot can break off and cause a stroke because of stasis in the atria
How to choose between rate and rhythm control to tx A fib?
- time, if sxs longer than 48 hours then you are at risk for stroke
Integrative approaches to A fib
- fish oil: lowers heart rate through interaction with Ca and K channels - omega 3: interacts with Ca and K channels - Magnesium: competes with Ca and causes relaxation of the heart and slows down conduction of AV node - Co Q 10: ATP production and helps mitochondrial function - L carnitine: there is a carnitine shuttle used in mito to help with break down of fat into energy
Atrial flutter - EKG findings - difference from fibrillation - what triggers rhythm - how do you measure? - tx?
- sawtooth pattern - The ventricle is fully contracting in this one, rather than just fibrillating - Re-entry along a fixed circuit - atrial to ventricle contraction ratio - longterm maintenance of sinus rhythm with CCB OR beta blocker and antithrombotic therapy - Could also do ablation for chronic sxs
Which anti-arrythmics are used for supra-ventricular arrythmias?
ABCD = A - Adenosine; B - Beta Blockers; C - CCB; D - Digoxin
Supraventricular tachycardia - EKG description - Tx - Rx
- no pwaves, lots of normal QRS complexes - Valsalva Maneuver (plug your nose, force air, but nothing is coming out) and then carotid sinus massage - Adenosine: beta-gamma goes over and activates K+ efflux & then the alphas are blocking calcium; lowers membrane potential; allows for a spontaneous depolarization at the SA Node; slows conduction through the AV Node and resets conduction
Why would you give a carotid sinus massage?
- external pressure on the carotid bulb stimulates baroreceptors in carotid sinus which increase vagus nerve activity and induces temporary slowing of SA nodal activity and AV nodal conduction
Adenosine - how is it given? Why? tox? - Adverse effects - interferes with
- given IV bolus because it has a rapid onset; have to give the drug very quickly so that it get to the site of action; It has a short duration of action which makes it great because the toxicities of the drug are very brief; so you would say that the drug has low toxicity - flushing, hypotension, bronchospasm (need to pay attention; because person will feel like they cannot breath, like they are dying), chest pain, HA - caffiene
What is affected with a STEMI to the LAD
- anterior, lateral, and septal parts of the left side of the heart
V-Tach - what do you see on EKG? - underlying mechanism in case of MI currently happening
- ventricular tachycardia - lots of wide QRS complexes - abnormal automaticity because of the ischemic event. In this particular case he doesn’t have scar formation yet, he’s still in the process of having the infarct, so his cells have become leaky. In addition to that, there’s an altered conduction formation as well and a reentry pattern.
V- Fib - what is it? - EKG - why is it so bad?
- Ventricular fibrillation - Lots of QRS complexes - Bad because with ventricles pumping that fast they are not effectively pumping out enough blood
Tx for MI
- CPR then initiate Advanced Cardiac Life Support
What is Advanced Cardiac Life Support?
CPR, shocking/defibrillate (if it’s a shockable rhythm, which in this case it is), Epinephrine and Amiodarone
Epi
- agonist for beta-1 adrenergic receptors in both nodal cells and myocytes - It’s positive chronotropy and positive inotropy
Amiodarone - MOA’s - Adverse effects - derived from??
- Acts as Class III mainly but has Class I, II, III, and IV activity. - Pulmonary fibrosis, thyroid abnormalities (bc of iodine) and major GI effects (anorexia and elevated liver enzymes), can also be proarrythmic - khella plant
Trosades de pointes - meaning - what is wrong? - what precedes it? - what different kind of wave is included? significance? - Tx? If induced by low K? - causes
- twisting of the points - polymorphic, widened QRS complex - long QT - U waves, can be caused by hypokalemia - depends on what caused the long QT and Torsades ; magnesium to cause K efflux from the cell which makes it hyperpolarize and unable to depolarize and if that doesn’t work then cardioversion - Genetic predisposition, Electrolyte abnormalities , Drug Induced: Some of the antiemetics, Macrolides, Class IA and Class III, Fluoroquinolones, Antifungals , Antipsychotics,Haloperidol, SSRIs, Methadone - an opioid
difference between cardioversion and defibrillation
The amount of voltage, what rhythm you can use it with, and whether or not it has to be synchronized with the rhythm
1st degree AV block - indications on an EKG - underlying mechanisms
- prolonged PR interval w/o any dropped beats - conduction block in the AV node
J points - when is it seen?
- there is an elevation at the very beginning of the ST segment where the S wave starts to turn into the ST segment - cases of left ventricular hypertrophy, specifically patients with chronic HTN
Mobitz Type I 2nd Degree AV Block a.k.a Wenckebach - indications on EKG - altered impulse or conduction - tx?
- Variable RR intervals, The PR intervals are not the same length - conduction - if there’s an additional block further down in the ventricles, like a bundle branch block or in EP study, you may consider a pacemaker there as well
Right and left bundle branch block
- Look at Lead V1 and V6. I - W appearance in V1 and M in V6, then the two L’s in William point you toward LBB Block - M appearance in V1 and W appearance or scooped S wave/very deep S wave appearance in V6 and the R’s in Marrow make it RBB Block
2nd Degree Mobitz Type II AV Block - EKG indications - what is happening? - Tx
- PR interval is long, The RR interval is irregular, and there are dropped beats - the atria fires and the ventricle wont fire - pacemaker
3rd Degree or Complete AV Block - EKG - what does that mean? - Tx chronic vs acute
- RR intervals are regular, PP interval is together, isn’t a P with every QRS - The P’s and QRS’s are dissociated and not matching up so atria are doing their own thing and the ventricles are doing their own thing, totally separately, - pacemaker and atropine
