Dumb question about hyperkalemia/hyperglycemia and depolarization~

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sommerwing

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1.) When a person has hyperkalemia, their extracellular potassium levels increase, making membrane potential more positive and causing the cell to get closer to depolarization.

2.) When a person is hyperglycemic, the increased glucuse causes inhibition of the ATP-sensitive potassium channel that channels K+ out of the cell. This increases the intracellular potassium levels in relation to the outside, causes membrane potential to become more positive and causes the cell to get closer to depolarization.


What in the world is going on here?
Increased extracellular potassium is making membrane potential more positive,
Decreased extracellular potassium is making membrane potential more positive.


How can both of these be true?

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1.) When a person has hyperkalemia, their extracellular potassium levels increase, making membrane potential more positive and causing the cell to get closer to depolarization.

2.) When a person is hyperglycemic, the increased glucuse causes inhibition of the (K+)-atp pump that pumps K+ out of the cell. This increases the intracellular potassium levels in relation to the outside, causes membrane potential to become more positive and causes the cell to get closer to depolarization.


What in the world is going on here?
Increased extracellular potassium is making membrane potential more positive,
Decreased extracellular potassium is making membrane potential more positive.


How can both of these be true?

Where did you read #2?
 
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I'll go over it:

Glucose enters Beta cells via a GLUT2 transporter.
Glucose the enters glycolysis, increasing the cell content of ATP

In increase in cell ratio of ATP:ADP causes ATP-sensitive K+ channels to shut down.
K+ transport to the extracellular is decreased.

The cell becomes closer to depolarization
, causing voltage-gated Ca2+ channels to open.


The important components are bolded. But yes, a decrease in transport of intracellular potassium to the outside causes depolarization.
 
1.) When a person has hyperkalemia, their extracellular potassium levels increase, making membrane potential more positive and causing the cell to get closer to depolarization.

2.) When a person is hyperglycemic, the increased glucuse causes inhibition of the ATP-sensitive potassium channel that channels K+ out of the cell. This increases the intracellular potassium levels in relation to the outside, causes membrane potential to become more positive and causes the cell to get closer to depolarization.


What in the world is going on here?
Increased extracellular potassium is making membrane potential more positive,
Decreased extracellular potassium is making membrane potential more positive.


How can both of these be true?

I'm a little confused here...

1. If someone has hyperkalemia, they have more extracellular K. Since K is a positive ion, shouldn't this lead to hyperpolarization and not depolarization? In other words, this INCREASES the difference in voltage between extracellular and intracellular compartments. This ultimately leads to hyperpolarization. I believe that lethal injection of K+ ultimately causes an individual to die from hyperpolarization.

2. It's been a while since I've reviewed my renal block, but I am sure that hyperglycemia (at least in diabetes) also leads to hyperkalemia (which leads to hyperpolarization). My understanding of how this happens is that the increase in extracellular glucose leads to an osmotic shift which consequently leads to potassium shifting from the inside to the outside of the cell. This is why insulin administration is part of the treatment of hyperkalemia. Insulin also upregulates K transporters into the membrane.

So, back to your original question. Increase extracellular potassium should hyperpolarize. Decrease extracellular potassium should depolarize, but this is not what happens in hyperglycemia.

That's my understanding of it at least..
 
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In a normal person (ie. no pathology), hyperkalemia will bring cells closer to threshold because it decreases the gradient for K+ to leak out of of cells. So, more K+ remains intracellular. The same thing is going on in the second example you gave -- more K+ is retained inside the cell. This is really happening in the beta cells and not so much everywhere. This brings the cell closer to threshold. It's the same exact concept though -- positive charge gets retained inside the cell.

In a person with DKA, you get hyperkalemia because of the H+/K+ exchange mechanism to buffer the acidosis -- protons move into cells and, to maintain electroneutrality, K+ moves out. So, you get hyperkalemia. It's not due to the hyperglycemia. It's due to the ketoacidosis. That's why, once you treat the acidosis, you also have to give the patient K+ so they don't become hypokalemic (some of the serum K+ moves back into cells and they also lost a lot of K+ in the urine, so their total K+ actually decreased even though they were hyperkalemic).

Does this answer your question?
 
In a normal person (ie. no pathology), hyperkalemia will bring cells closer to threshold because it decreases the gradient for K+ to leak out of of cells. So, more K+ remains intracellular. The same thing is going on in the second example you gave -- more K+ is retained inside the cell. This is really happening in the beta cells and not so much everywhere. This brings the cell closer to threshold. It's the same exact concept though -- positive charge gets retained inside the cell.

In a person with DKA, you get hyperkalemia because of the H+/K+ exchange mechanism to buffer the acidosis -- protons move into cells and, to maintain electroneutrality, K+ moves out. So, you get hyperkalemia. It's not due to the hyperglycemia. It's due to the ketoacidosis. That's why, once you treat the acidosis, you also have to give the patient K+ so they don't become hypokalemic (some of the serum K+ moves back into cells and they also lost a lot of K+ in the urine, so their total K+ actually decreased even though they were hyperkalemic).

Does this answer your question?

yes but insulin also required to bring K+ into the cell, it's both mechanisms (acidosis and low insulin levels) that cause the hyperkalemia.
 
yes but insulin also required to bring K+ into the cell, it's both mechanisms (acidosis and low insulin levels) that cause the hyperkalemia.

:thumbup: AFAIK, co-administration of K with insulin is pretty much standard for this reason. I think the reason it happens is just increased Na/K atpase activity though, correct?
 
In a normal person (ie. no pathology), hyperkalemia will bring cells closer to threshold because it decreases the gradient for K+ to leak out of of cells. So, more K+ remains intracellular. The same thing is going on in the second example you gave -- more K+ is retained inside the cell. This is really happening in the beta cells and not so much everywhere. This brings the cell closer to threshold. It's the same exact concept though -- positive charge gets retained inside the cell.

In a person with DKA, you get hyperkalemia because of the H+/K+ exchange mechanism to buffer the acidosis -- protons move into cells and, to maintain electroneutrality, K+ moves out. So, you get hyperkalemia. It's not due to the hyperglycemia. It's due to the ketoacidosis. That's why, once you treat the acidosis, you also have to give the patient K+ so they don't become hypokalemic (some of the serum K+ moves back into cells and they also lost a lot of K+ in the urine, so their total K+ actually decreased even though they were hyperkalemic).

Does this answer your question?

Ahhh yes. Silly me forgot to consider the concentration gradients =)

So, to summarize:

1. Hyperkalemia will increase the voltage gradient (tending to hyperpolarize) but will also decrease the concentration gradient (tending to depolarize). According the Nerst Eq shows that the concentration gradient has a stronger "pull", ultimately leading to depolarization.

2. After a quick review to my renal notes, there are a few situations to consider. In the presence of hyperosmolar state, the hyperkalemia is due to "solvent drag" caused by osmotic pull of water from inside to outside. In the specific case of acidosis, hyperkalemia is caused by H/K exchange. In setting of low insulin levels, hyperkalemia is also seen because it is required for K to enter the cell (K+ channels brought to cell surface as well as increase Na/K activation). In the case of DKA, you have all three of these factors contributing: 1) hyperosmolar state (hyperglycemia), 2) acid conditions, and 3) Low insulin levels.

FYI, Insulin is also used for patients with JUST hyperkalemia, but since they are not hyperglycemic then continuous glucose transfusion is used concurrently to prevent hypoglycemic episode. Above poster also mentions giving insulin concurrently with K.

Great review =)
 
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:thumbup: AFAIK, co-administration of K with insulin is pretty much standard for this reason. I think the reason it happens is just increased Na/K atpase activity though, correct?

yeah i believe that's the mechanism...just kind of weird that both T3/T4 and insulin both increase the ATPase, but that's endocrine for you
 
Although these factors are indeed causing membrane depolarization, they are actually making neurons less likely to fire an action potential because the depolarization process is gradual. I think it's called adaptation, where you have gradual shifting of the Na channels into their inactive form as the potential becomes less negative. That's why hyperkalemia causes muscle weakness instead of tetany
 
1.) When a person has hyperkalemia, their extracellular potassium levels increase, making membrane potential more positive and causing the cell to get closer to depolarization.

2.) When a person is hyperglycemic, the increased glucuse causes inhibition of the ATP-sensitive potassium channel that channels K+ out of the cell. This increases the intracellular potassium levels in relation to the outside, causes membrane potential to become more positive and causes the cell to get closer to depolarization.


What in the world is going on here?
Increased extracellular potassium is making membrane potential more positive,
Decreased extracellular potassium is making membrane potential more positive.


How can both of these be true?

There is alot of good information already in this thread, but I think some people are missing the point of your question. Your question involves membrane potential and how it is related to ion concentration and their permeability. Here is your answer from a purely physio chemical-electrical-permeability point of view without any mention of Na/K pumps and insulin and such.

1) You decrease the concentration gradient for potassium across the membrane. This makes the equilibrium potential for potassium less negative(going from -80mv to say -60mv). Therefore it makes sense for the cell to become slightly depolarized. As the above poster mentioned this can actually lead to a decrease in action potential firing due to a process called accommodation. The mechanism of this process is due to the gradual depolarization of the cells causes Na channels to slowly move into the inactive phase.

2) Yes, you may be increasing the intracellular K of the beta cell in this scenario, but it is negligible(going from 140 mM K inside the cell to say 143 mM K). This will have very little effect on the equilibrium potential. What is happening is a decrease in cellular permeability to potassium. This causes a depolarization through a mechanism that is sort of complicated, and I won't try to explain. However, the numbers work perfectly if you use the Goldman-Hodgkin-Katz equation wiki. Basically, the idea is you reduce the permeability this leads to the potassium concentration being less effective at determining the membrane potential, and other ions play a larger role(like sodium) now that potassium has decreased permeability.


To summarize. Situation 1) is mediated by changes in extracellular potassium levels. Situation 2) is mediated by changes in permeability to the potassium.

Ion concentrations don't play the whole role in membrane potential. It is also their permeability.

Remember there is a huge concentration difference between intracellular and extracellular sodium, yet the membrane potential at rest pretty much entirely depends on potassium. This is due to the cells much higher permeability for potassium than sodium at resting membrane potential.
 
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