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 Hyperkalemia and Hypokalemia  

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I got a few question about the effect of potassium concentration:

As far as I know, hyperkalemia causes the resting membrane potential to be more negative, so that makes an action potential harder to achieve. And hypokalemia causes the resting membrane potential to be more positive, so that makes an action potential easier to achieve.
(correct me if I were wrong.)

Here are my questions:
1.If the former statements were correct, than it would explain why hyperkalemia causes muscle weakness, paralysis, and cardiac depression(no action potential, no muscle contraction). But what's the reason that hypokalemia causes muscle weakness,too?

2.How to explain the ECG finding of hyper- and hypokalemia? ( Hyperkalemia: shallow, wide QRS with tenting T wave; Hypokalemia: low T wave)


hyperkalemia depolarizes the memebrane...
hypokalemia hyperpolarizes the membrane...


At resting membrane, concentration of K in the cell is very high, and in the extra-cellular fluid is slow :arrow: there is a passive flow of K out of the cell

:arrow: Hyperkalemia, extracellular K is high :arrow: prevent the passive flow :arrow: more K in the cell :arrow: depolarization

:arrow: Hypokalemia, extracellular is slow :arrow: stimulate passive flow :arrow: more K goes out of cell :arrow: hyperpolarization


I absolutely agreed what you mentioned above. But do anyone know what is the mechanism of the followlin sentence--->[Hypokalemia, as predicted by the Nernst equation, hyperpolarizes the resting membrane potential to more negative values, and consequently may cause slowing of conduction . In addition, hypokalemia decreases potassium conductance and may enhance automaticity] . I confused that hypokalemia decreases potassium conductance but enhances automaticity.


Effects of hyperkalemia:

1. increased excitability due to decreased resting membrane potential (less negative potential, so closer to the treshold value)

2. decreased amplitude of action potential (amplitude is measured from the resting value to the spike value, and with hyperkalemia the resting value is decreased and so as the amplitude)

3. the main effect is: due to decreased potassium concentration gradient, repolarization is prolonged (refractory period is prolonged) so the frequency of action potentials is decreased


here is wht i found in katzung !

tht's a nice explanmation by mildus, just to add!

a/c to bighear he is right to say tht potassium concentration hasa more to do with the permeability rather than resting membrane potential!

Hyperkalemia: reduces eq. potential for K+ but on the other hand increases permeability therefore potassium current will be higher and RMP will come closer to K+ eq. potential!

significance: in cardiac pacemaker cells during phase IV ,due to high K+ permeability it will effectively counteract hyperpolarization induced depolarizing current via rectifier channels therefore late approach towards threshold!

Hypokalemia: increases eq. potential for K+ but on the other hand reduces permeability ;therefore K+ current will be low and RMP will be farther away from the eq. potential (K+ eq. pot. has the major influence on RMP) in other words membrane will be destabilized!

significance: in cardiac pacemaker cells low K+ current during phase IV will not be able to effectively counteract the depolarizing current and therefore early approach towards threshold [enhanced automaticity]


^ .. ?

Edited by alirizvi on Jun 03, 2010 - 12:53 PM


This confused me terribly when I thought about the RMP but it makes more sense from a permeability aspect.

Potassium efflux is mainly a passive process according to the concentration gradient. So if the outside is very high (hyperkalemia), there will be a reduced efflux of [K]+ which maintains the depolarisation.

And remember the Na-K ATPase channel is still pumping away. 3 Na+ out and 2K+ in.

It kind of makes sense to me! nod


An easy way to to understand this process is to remember that Em essentially represents the potential energy across a membrane. This might help understanding.

RMP is determined mostly by K+ due to its high conductance (permeability/leakiness) at rest. Two forces are essentially at work in determining the potential energy: electrical gradient and chemical gradient.

The electrical gradient is set up by the negative interior of the cell (proteins, nucleic acids, etc) and the positive exterior (Na+, Ca2+, etc.). In the case of K+ (a positive ion), the negative intracellular charge and positive extracellular charge resist its flow out of the cell.

In the case of RMP, the chemical gradient is determined by the intracellular [K+] (high) and extracellular [K+] (low). In this case, the K+ gradient heavily favors movement out of the cell.

Since, for all intents and purposes, only K+ conductance is high at rest, the electrical and chemical forces on K+ will reach an equilibrium which we call RMP.

If the extracellular [K+] increases, the K concentration gradient between the ICF and ECF decreases. Specifically, there is a reduced gradient and less force influencing K+ movement out of the cell. Intuitively, more K+ in the ECF is also going to change the electrical forces at work, specifically resisting K+ movement out of the cell. In this setting, less K+ leaks out of the cell and a new equilibrium is reached with less potential energy at RMP (depolarized).

If the extracellular [K+] decreases, the opposite occurs. The K+ gradient between the ICF and ECF increases. This increased gradient (both concentration and electrical) results in a high driving force influencing K+ movement out of the cell. The result is passive leakage of K+ out of the cell where a new equilibrium is reached with more potential energy at RMP (hyperpolarized).

Thus, hyperkalemia results in depolarization from RMP, and hypokalemia results in hyperpolarization from RMP.



This is a great response to the question put forward. If I can add my 2 cents....

When we say hyperk+ results in depolarization from RMP what does this mean?

As discussed above RMP depends on a gradient of intracellular K+ to extracellular K+ (intra high, extra low). When extracellular K+ levels become elevated the RMP becomes less negative and moves closer to threshold potential. Lets say that RMP is -70 and threshold is -40 in normal myocytes. Now lets say in hyperK+ the RMP becomes less negative to -50 and threshold is still -40. This causes less Na+ channels to open during phase 4 in pacemaker cells. We know that Na+ is the main ion that increases the rate and rise of phase 4 (automaticity) which leads to Ca++influx during phase 0. This is why pacemaker cells in the SA node lose automaticity. Less Na+ channels open, less Na+ enters sarcolemma=THE RATE AND RISE OF PHASE 4 IS DECREASED leading to bradycardia's, and loss of overdrive suppression. The AV node takes over until it is blocked, eventually ventricular cells take over=bad news.

The RMP may even lay above the threshold potential so subsequent action potentials will become weak and pathetic in contractile myocytes (remember in contractile myocytes phase 0 is dependant on fast acting Na+channels).

The reverse happens in HypoK+ where the RMP becomes more negative....lets say to -100mV. This allows more Na+ channels to open which leads to increase Na+influx leading to increased automaticity and increases the opportunity for reentry ect...

Hope this helps.


Thanks Burgess! That is very good!


I've been reading this for my condition. I understand what is being said. Saying this, I'm not a med student, physician, but have worked in the medical field for 10+ years. Can someone please put it in layman terms like I was a patient? I'm not asking for medical advice, but don't like muscle spasms waking me up, and can never keep enough K+ in my system. Any advice on details for basic self maintenance? Or at least how to minimize the reduction of the K+ shortcomings? Thank you from the bottom of my +ion!


Potassium is important because it helps in the functioning of almost all important organs of the body like heart, kidney etc.


@ FrankLee

Sorry it has been so long.

Basically, if you have high K+ then your nerves are more excitable. If you have low K+ then your nerves are less excitable.

You muscle spasms may be from lack of normal neural "input" to your muscles perhaps...? I am not sure. How are your calcium levels?

If your K is chronically low, eating more bananas will help and perhaps a K-sparing diuretic (spirinolactone, or amiloride) may help.



Can someone explain the effects on an ECG as originally asked in the first post


everyone should read this page and your concepts will be clear


There is a mix of some good and a lot of plain wrong information in the posts above. Thanks to Jamshaid007 for an excellent resource filled with all the correct explanations.

In terms of myocardium cell potential:
hyperkalemia = depolarized resting potential, but Decreased excitability. Shortened action potential duration.
hypokalemia = hyperpolarized resting potential, but Increased excitability. Prolonged action potential duration.

In terms of EKG surface potential:
hyperkalemia = shortened QT, peaked T wave, wide QRS, ST depression
hypokalemia = prolonged QT, flat Twaves, U waves

The confusion comes from the fact that these action potentials are a lot more complicated than what there is time to cover in most Physiology courses. Sorry for the long post below but it is necessary if you don't want to memorize the above and want to answer these "why" questions.

3 important concepts:

1) Some Na Channels will begin opening while the RMP is below "threshold potential".

Threshold voltage of a cell is not a fixed magical voltage level where all of the sodium channels suddenly turn on. Sodium channels are voltage-gated and turn on probabilistically. The more positive the membrane voltage, the higher the probability a sodium channel opens. So even at very negative voltages, most sodium channels stay closed. Occasionally a sodium channel may open briefly. These brief openings conduct such a small current that they have very little effect on the RMP. At these very negative RMP values, the only channels that are open significantly are "leak" K channels and thus the RMP (which is kind of a weighted average of the reversal potentials of all the conducting ions) remains close to the K reversal potential. Now the (maybe to some) surprising part: if the membrane voltage depolarizes a little bit but is still significantly below (more negative to) normal "threshold potential" of a cell, some Na channels will start opening (although most stay closed). Again this is because Na channels are probabilistic and voltage dependent with no sharp cutoff in their voltage dependence right at "threshold". Since you membrane voltage has depolarized some, the probability of Na channels opening is no longer close to 0 and some of them will start opening (even though you are below "threshold").

2) Threshold voltage is kind of a moving target that depends on the size of Na and K currents relative to each other.

At subthreshold depolarizations of membrane voltage, the opening of some Na channels does pull the membrage voltage higher (depolarizes) but as long as there is significant K current pulling the membrage voltage towards hyperpolarization, the Na current is sufficiently offset by the K current and the membrane voltage remains "subthreshold". The "threshold" phenomenon occurs when membrane voltage is elevated enough that a large enough number of Na channels open to overcome the K channels. The membrane voltage is like a weighted average so as Na channels open, voltage is pulled towards the Na reversal potential (positive) from its resting state close to the K reversal potential (negative). If enough Na channels open to overcome the hyperpolarizing influence of the K channels, the effect becomes a positive feedback loop: as Na channels open, the membrane voltage becomes more positive and as it becomes more positive, more Na channels open. This Na channel positive feedback causes the rapid phase 0 depolarization of the action potential. It would run away unchecked if not for the fast inactivation of Na channels and a second set of K channels the voltage gated K channels (as opposed to the leak K channels). These K channels' voltage dependence is shifted more positive compared to the voltage gated Na channels and so they turn on later at more positive voltages, helping to drive membrage potential back to ward the negative reversal potential of K.

3) Sodium channels inactivate after opening.

In activation is a process that makes Na channels non-conducting after being open. We talked about fast inactivation of Na channels (ball and chain mechanism). There is also a slow inactivation (due to more overall conformational change of the Na channel protein). Hyperpolarization relieves inactivation and resets the Na channels making them ready to fire. At depolarized voltages, Na channels can open and some can go on to become inactivated. This effect is key to the physiological effects of hyper/hypo kalemia.


Reversal potential of K is shifted positive. Driving force for K to leave the cell is decreased so there is less "leak" K current and the RMP is depolarized compared to normal. The more positive RMP means more Na channels will randomly open and more of them will become inactivated. This means fewer Na channels are available to respond by opening when depolarization occurs. This effectively ALSO RAISES THE THRESHOLD POTENTIAL. Because there are fewer Na channels available to conduct current, you need a greater voltage to get enough Na current to overcome the effect of the K channels. Thus the "threshold" voltage, the voltage where Na wins over K, is now higher. Early in mild hyperkalemia, the effect on K currents and RMP is more important than the effect on Na channels and Threshold potential, so overall there is a small increase in excitability as the RMP is slightly closer to threshold potential. Soon however, the hyperkalemia's effect on the Na channel inactivation dominates and you get an overall DECREASE in excitability due to decreased availability of Na channels for phase 0. This results in a slow phase 0 depolarization and a slow or widened QRS complex.


Essentially reverse of above. Low serum K = shift negative in reversal potential of K = incr K driving force = more leak K current and hyperpolarized RMP. This causes increased availability of Na channels for firing due to relief of inactivation and actually shifts threshold potential towards the negative. Thus there is NOT as increase in the "distance" of the RMP from threshold. Increased Na channels = faster depolarization and lower threshold voltage = INCREASED excitability.

The flat/peaked T-waves are a little more complex: the voltage dependent K channel proteins like to have a potassium ion sitting in the pore near the extracellular end of the channel. This helps keep them conducting and prevents them from collapsing shut. In hypokalemia, there is decreased extracellular K, so more of the voltage gated K channels are collapsed shut. In hyperkalemia, very few of these voltage gated K channels are collapsed and many more of them are ready to fire when the cell depolarizes sufficiently. Thus in hyperkalemia, more K current after depolarization (ie after phase 0, so during phase 2 and 3) means, phase 2 is shortened and phase 3 is faster. This results in shortened QT and peaked T wave. Opposite in hypokalemia - collapsed K channels = less K current in phase 2 and 3 = long phase 2 and slow phase 3 = long QT and flat T wave.

SA node:
HR changes are not a typically discussed as part of the cardiac syndrome caused by hyper/hypo kalemia. Take fhe following with a grain of salt. This is what makes sense but really it is much more complex than our discussion.

I did want to mention regarding phase 4 depolarization that although a Sodium current is involved and K currents also become important in phase 4 (in response to Acetylcholine) the channels involved are different in terms of both the Na and K channels than those mentioned earlier so do not confuse them. Phase 4 is a balance of Na and K currents where there is normally enough Na current to slowly overcome the K current and depolarize to threshold. These SA node phase 4 Na channels open at much lower voltages and have a very different voltage dependence than the myocardium phase 0 Na channels. Here the K concentration effects are more intuitive. Hypokalemia means a large difference in K across the membrane = large K efflux = hyperpolarizes RMP, making it closer to reversal potential of K (negative) and farther from threshold. Also the increased K efflux means the slope of phase 4 depolarization is flattened as the Na current must fight against a larger K current. The Na channels in the SA node DO NOT INACTIVATE with slow inactivation at subthreshold voltages and thus we don't have to worry about them the way we did before. Farther from threshold with slower rise in voltage = slower HR = sinus bradycardia associated with Hypokalemia. Hyperkalemia would do the opposite - depolarizes RMP and steepens phase 4 depolarization and thus increases HR.

In terms of weakness, some hand waving is necessary. Decreased excitability will obviously present as weakness but increased excitablity can also cause weakness through "fatigue"-type effects. Furthermore, the K changes will have myriad changes on other ion transporters directly and indirectly by changing other ionic gradients. Both hyper and hypo kalemia cause problems in conduction. You need correct amount of K for conduction, not excessive nor too little (that is why they both cause pathological ECG changes). The discussion above is for myocardium and EKG findings. Behavior may be somewhat different for nerve and skeletal muscle.

PS> I am thinking to start a USMLE related blog so please post there if you have any more questions on any topics. Thanks.

Edited by mcscrooge on Aug 12, 2014 - 9:09 AM


mildus nice explanationwink


I have one more doubt in this topic.

How does acute hyperkalemia increase neuronal excitability and chronic hyperkalemia decrease neuronal excitability?


@drvnm its simple.
In acute hyperkalemia, excitability increases bcoz membrane potential is less negative. But keep in mind that hyperkalemia keeps the cell in constant depolarization. With constant depolarization the Fast Na channels cannot re activvate( as they need the cell to repolarize for activation again). So in chronic hyperkalemia due to Na channels remaining in open state neuronal excitabilty decreases. Hope it clear things up. smiling face

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