Abnormal Electrophysiology Flashcards
What is common in hypo and hyperkalemia
Both cause depolarization in the resting memrbane potential of atrial and ventricular myocytes.
Repoalrization stops prematurely in both of the condition and as a result there are less Na channels available for depolarization. This decreases the Na current during upstroke of action potential.
- Threshold potential is more positive
- Lower conduction velocity
- Lower amplitude of action potential
- The rise of action potential is less rapid
What is the voltage clamp technique and what is its significance
It is a technique where there is depolarization in the resting membrane potential, repolarization stops prematurely and as a result the number of active Na channels are decreased, this causes lower Na influx into the cell, lower Na current, lower amplitude of AP, decreased conduction velocity of AP, rate of rise of AP is decreased and threshold potential is more positive.
Stroke volume is reduced, duration of stroke volume is more, contractile performance is impaired and MAP is lower, cause the CO to be lower
What is he trying to explain here
The threshold potential have now become more positive and so excitability will be reduced since the threshold potential is higher now. This is an extension of the last slide. This happens in both hypo and hyperkalemia
What happens to the E(K) - the nernst potential in hyperkalemia
According to the nernst equation, the K nernst potential becomes more positive (the resting membrane potential becomes more positive as a result)
What happens to the E(K) in hpokalemia
E(K) becomes more negative than normal, we can see that from the nernst equation
Hypo and hyperkalemia conductance, K current and AP duration
- Conductance is directly proportional to [K]
- Hypokalemia: conductance decreases, K current decreases, duration of AP is increased
- Hyperkalemia: conductance increases, K current increases, duration of AP is reduced
What does the T wave measure in EKG and what happens to it in hypokalemia and hyperkalemia
The T wave measures the start of phase 3 and ends at the start of phase 0. EKG measures the rate of change of the T wave.
In hypokalemia, there is reduced current of K and hence as a result the T wave will be flatter since the slope of phase 3 has decreased,
In hyper, there will be a short (kind of a spike) form of T wave since the slope of the phase 3 has increased
Now explain why there is resting membrane potential in hypo and hyperkalemia
- In hypokalemia the conductance of K decreases and as a result the conductance of Na increases. Hence there will be depolarization at the resting membrane potential. Even though E(K) has increased but the increase is not big enough to balance out the decrease in conductance of K since you have to take the log of [K] to calculate nernst potential
- In hyperkalemia the nernst potential of K is more positive (usually it is -80 mV) so because of this there will be depolarization at resting membrane potential and also the conductance increase but he said an increase in nernst potential of K is the major factor
If the conductane of an ion is increased what happens to the resting membrane potential
The resting membrane potential will be get closer to the nernst potential of that ion
What is he trying to explain here
In hyperkalemia 2 things are changing the nernest potential of K and K condutance. The nernest potential is becoming more positive as an increase from 5 to 10 of [K] will cause the nernst potential to be -62 mV instead of -80 mV which will cause the resting membrane potential to be more positive. That is why the an increase in nernst potential of K is the major factor for resting membrane potential depolarization in hyperkalemia.
Also the distance between V and Ek is becoming less and less due to increase in gK
This explain hypo and hyperkalemia perfectly as why the resting membrane potential is becoming more positive
In hypokalemia the resting membrane potential goes away from K nernest potential due to a decrease in the conductance shown by the left side of the graph, hence becoming more positive
The effects of hyper and hypokalemia on SA node cells
The effect is solely due to condutance, MDP becomes more negative in hyper and more positive in hypo. In hypo there is always tachycardia since the MDP is closer to threshold potential but tachycardia may not always be seen clinically.
Hyper has bradycardia which may also not always be seen clinically
What happens to phase 4 in hypo and hyperkalemia in the SA node (we are talking about the phase 4 of the SA node here, it is important to know that)
phase 4 is more steep in hypo and less steep in hyper
What happens to phase 3 in hypo and hyperkalemia
phase 3 is less steep in hypo and more steep in hyper
Why dont you see bradychardia in hyperkalemia
The baroreflex changes the sympathetic firing to compensate for low CO
Just remember that the QRS widens in both of the cases
What is the significance of U wave
It is characteristic of hypokalemia, it is not known why it occurs and it takes place after the T wave
Flaccid paralysis
In hypokalemia there is impaired Na current as there are less active Na channels available for depolarization. This will cause the patients to have diminished ability to contract their limbs as the skeletal muscle function is impaired. This is called flaccid paralysis
What is the treatment for flaccid paralysis
Fix K levels by infusing K via IV. Care has to be taken as not to make them hyperkalemic
How does the T and U waves change in this treatment process
When K is given in IV to corrent hyopkalemia the T waves become shorter duration and higher in amplitude whereas the U waves disappear
What are the methods used to reverse the effects of hyperkalemia
- Give Ca in the form of Calcium Gluconate which has the fastest onset.
- Give NaHCO3, slower onset
- Glucose and insulin, even a slower onset
- Diuretic , slowest onset
How does each of these 4 methods help
Ca shift the Na inactivation channels to a more positive membrane potential which causes an increase in the number of available Na channel in a given time
- NaHCO3 INDIRECTLY increases the activity of Na-K pump activity
- Insuline stimulates the Na-K pump, which moves extarcellular K into the cell, this DIRECTLY increases the Na-K activity
- Diuretic enhances the excretion of K from the kidneys.
It is important to remember that insulin DIRECTLY increases Na-K pump activity and bicarbonate INDIRECTLY increases its activity
What does hypercalcemia do to the inactivation gate of Na
It is important to remember that by increasing Ca will not correct the underlying problem which is more positive membrane potential
What happens in a person who has hypercalcemia and has normal levels of K
In a person with normal K levels, the inactivation channels are already open so there is no benefit for having higher amounts of Ca to shift the inactivation curve to more positive potential.
However, the activation channel curve is also activated to a more positive potential so excitability is decreased. Threshold as a result is shifted to a more positive potential (this also happens in patients with hyperkalemia this also happens but the benefits of having more positive Na inactivation curve outweighs the harm of having Na activation channel at a more positive potential)
How does bicarb work? What is the specific mechanism
When sodium bicarbonate is released in the ECF, the pH increases, [H] drops causeing the Na-H pump to pump out more H into the surrounding and at the same time it pumps more Na into the cell.
This indirectly activates Na-K pump to work faster and balance out the increase influx of Na into the cell. This method is indirect and it is important to know that. Insulin acts in a direct way.
What happens in hypoxia
- Insufficient O2 reaches the heart cells
- Less ATP is made.
- Ca L channels have to be p’s so that they open which requires ATP. With reduced availability of ATP, some of these channels stay closed
- As a result phase 2 shortens, however the resting membrane potential stays the same
What happens in Ischemia? What is different about hypoxia and ischemia
- In ischemia there is reduced blood flow to the heart
- During every action potential some K leaks out of the cell which is then carried away by the blood (since [K] is high intracellularly). In ishcemia this excess K is not taken away leading to localized hyperkalemia
- This causes the resting membrane potential depolarization, resting membrane potential is more positive than normal
- This also impairs the Na current and leads to similar effects as previously talked about in hyperkalemia
It is important to know the difference between ischemia and hypoxia
What changes on EKG that would show ischemia, how can you explain this change
There is ST segment elevation in ischemia (not in hypoxia) which is seen becuase of the resting membrane potential becoming more positive
What is the point of this slide
If you look at the Ca curve we can see that the membrane potential becoming more positive will not significantly reduce the number of open Ca channels. So the number of active Na channels decreases, but the available active Ca channels remain the same
Summary of hypoxia and ischemia
The only difference is in the resting membrane potential
How does hypokalemia can cause arrythmias
It can cause reentry loops to happen since the K current is reduced so the repolarization phase takes longer
What are the causes of arrythmia
- Increased sympathetic nerve firing: This can be due to enahnce beta-adrenergic agonists, decreased K conductance as in hypokalemia, flow of current from ischemic region to a normal healthy region
2, EAD and DAD: Early and delayed after depolarizations that causes abnormal conduction such as reentrant loop
EAD
Early After Depolarization:
There are 2 factors that contribute to this
- Reduced K current, phase 3 is longer
- Ca window current, inactivation gates start to open before all the activation gates have closed, this generates a depolarizing current and further prolongs the action potential
As a result the duration of the action potential is increased which can lead to reentry loops
What is the significance of arrythmias in terms of the Ca window
There is generation of the Ca window current illustrated by the graph right here.
Usually activation gates open at depolarization with the inactivation gates being closed. The inactivation gates can open prematruely if there is a reentry loop while the activation gate never got a chance to close. This happens due to Ca window presence and it is called the Ca window current
How does Ca window current can make the membrane potential more positive
Normally all of the activation gates close before any of the inactivation gates open. This may not happen sometimes as the inactivation gates can open before the activation gates closing due to reentry loop and due to the presence of Ca window.
When this happens, Ca moves into the cell, depolarizing the membrane potential, making it more positive
Why doesnt normally this happen? Why doesnt the inactivation gates open again at a time when the activation gates are still open on Ca channels
Normally K repolarizing current is fast enough to cause the activation gates to shut close and then the inactivation gates to open.
This doesnt happen at lower K current
What does cocaine do to the heart
- It messes the delayed rectifier K channels which causes a lower K current and prolongs the phase 3.
- Cocaine also blocks the reptake of norepinephrine by sympathetic nerve firing cells. Epinehrine usually causes a larger Ca current by decreasing the openin potential of the Ca channels to a more negative potential (so the Ca window increases) . So the continuous availibility of epinephrine will cause an increase in Ca window, making reentry loops more probable
When do DAD and EAD occur
EAD in phase 2 or early phase 3 and DAD in phase 4
DADs
Delayed After Depoalrizations: These are associated with
- High heart rates that cause accumulation of Ca within the myocytes - there is not enough time to pump all Ca out of the cell
- Increased cytosolic Ca activate
a. Na/Ca exchnages, for every 3 Na that come in 1 Ca move out, this is a net depolarizing current - membrane potential will become more positive
b. a non specific cation channel that allows extracellular cations to enter the cell
Summary for EAD and DAD
What cells are associated with DAD and EADs
Remember that tachycardia is associated with DAD.
Midmyocardial cells are associated with DADs and EADs. They are the ones that trigger the Na-Ca pump and the non selective cation channel
What is the significance of M cells
The M cells already have a much longer duration of action potential as compared to all other heart cells as shown by the picture
What are the characterisitcs of M cells
- They prolong the duration of AP either than epicardium or the endocardium cells
- They have less of K current within these cells that slows the rate of repolarization
- Na current is small, prolongs phase 2, doesnt matter that much though
- They have a very large Na-Ca exchange current which also provides an inward current that prolongs phase 2
- They develop EADs when K current is reduced
- They develop DADs in response to agents that cause Ca overload or a higher heart rate
For the last 2 epicardium and endocardium do not
Can you see EADs and DADs in EKG
No, but if there are sufficient myocytes in the rentrant loop, there can be enough depolarizing current to trigger a reentrant loop in the adjacent tissue
Most signigicant reason of the reentrant loop
The length of the AP, or the length of the tissue undergoing AP has to be less than the anatomical length of the loop of AP. This is why hypertrophy of the left ventricle increases the chances of reentrant loop since more tissue has to simultaneously undergo action potential
Formula for amount of tissue depoalrized by the action potential
Amount of tissue depolarized by AP = Conduction velocity x duration of AP
Same thing as distance = speed vs time
Which current affects conduction velocity and which affects duration of AP
Na for conduction velocity and Ca and K for duration of AP
What is the treatment for EAD
Give beta andrenergic antagonist. This causes the K current to decrease, the duration of AP increases and hence the reentry loop would be blocked (conflicting his own words)
What are the reasons for long and short QT syndrome
Long QT syndrome is due to less K current and short QT interveal is due to higher K current
