In the ICU, we are at times obsessed with making our patients “euboxic” or, more clearly stated, all labs values within normal ranges. That being said, electrolytes are something we replete every day and our nurse friends often have protocols which instruct them on how to manage and correct these derangement to hopefully optimize the outcomes of our patients. When I was a resident, one of my mentors and a good friend to this day, Dr. Mike Ruiz, taught me to correct the magnesium (when hypomagnesemia is present) before correcting the hypokalemia (potassium deficiency) in patients who needed their electrolytes repleted.
This left me scratching my head. It made no sense. I’m no biochemist. I’m trying to write notes here! And then he went on to explain the mechanisms. My mind was blown. How much other stuff do I not know? How come I wasn’t taught this in med school? Well friends, there A LOT that we weren’t taught in med school or even residency and fellowship training, for that matter.
That pretty much why I’m on this lifelong learning journey and hopefully bringing you all along for the ride. I can’t say I remembered the exact mechanisms when he taught them to me. More importantly I remembered that “that’s just the way it works” like many of us do for complex processes. Here, we are going to dig in to why we replace magnesium before potassium.
Before we move forward, I would like to give a shout out to Dr. Tony Breu (@tony_breu). His explanation on the matter is by far the best. I have attached his twitter feed on the matter on this post.
When replacing potassium for hypokalemia does not work.
Here’s the deal. When patients have hypokalemia, you want to fix it. So you give potassium to make the numbers pretty. You go ahead and give some potassium and do what the protocol says to do: recheck. Labs come back, poor patient got stuck for these labs. Potassium burned a bit on the way in because the IV was acting funny. Low and behold, the potassium did not go up. What just happened? Where did it go?
Did you check the magnesium level prior to fixing the hypokalemia?
Did you check the magnesium level? Probably not. Per the cited article, more than 50% of hypokalemia patients have concomitant hypomagnesemia. In my ICU patients, I check the basic metabolic panel (BMP) along with magnesium and phosphorus almost daily. Only on patients who need it, of course. No point in being wasteful.
But the point here is that there’s an association between hypomagnesemia, or magnesium deficiency and hypokalemia. Until you fix the hypomagnesemia, you can’t fix the potassium. Think about it like tipping the bouncer to be able to get into the club. My Miami days are coming back to haunt me.
Why are hypomagnesemia and hypokalemia related?
Why does this happen though? We can get all science-y on this since you’re interested.
It was initially suggested that Na-K-ATPase pump impairment in the kidney and GI tract was caused by the hypomagnesemia. Therefore, potassium wouldn’t be able to be taken in by the renal cells (I’ll specify which ones soon) from the plasma/serum/blood. This would cause the patient to urinate away the potassium because of a decreased uptake of potassium. This didn’t really make sense to me.
Why would the cell waste/excrete potassium in to the urine if the Na-K-ATPase pump was broken? Shouldn’t this make the intracellular potassium stay the same and the serum potassium go up? The body is smarter than this, I thought. I’ll explain later. To add to this, potassium is mostly reabsorbed from the urine in the proximal tubule and the loop of Henle. Potassium secretion happens a little later, in the distal convoluted tubule and cortical collecting duct. It turns out that magnesium replacement decreases this secretion into the urine. I know what your next question is going to be.
How does magnesium decrease the secretion of potassium?
This is where things get really nerdy. Hang on tight. The article might do a better job explaining it than I can. Besides, they have pretty pictures. Let me take a stab at it. I always get baffled and amazed at how these folks figured this out. All this fun stuff is taking place in the distal convoluted tubule and the cortical collecting duct cells in the kidneys.
First, how does potassium get into the cells from blood?
Potassium has to come in to the cell via somewhere. That somewhere is the Na-K-ATPase channels. Cool. Blood to cell via Na-K-ATPase channels. Got it.
How do we end up secreting the potassium via our urine?
In the distal convoluted tubule and the cortical collecting duct cells, the following two channels, ROMK and maxi-K, are responsible for the potassium excretion into the urine. Those are the ways out of the cell and into the urine.
What does magnesium have to do with ROMK channels and hypokalemia?
Well, magnesium inhibits the ROMK channels at certain intracellular concentrations. If your patient has low magnesium (hypomagnesemia), then the ROMK is going to want to waste away the potassium, making the patient hypokalemic. The flood gates will remain open. This means that until the magnesium is fixed, you can’t fix the hypokalemia. There are other components like sodium and aldosterone who play a role in this, but that is a bit too esoteric for my tastes. There’s still much for us to learn.
Why does low magnesium cause hypokalemia?
Let’s wrap it up. Potassium cannot go from plasma into the cells of the kidney unless the Na-K-ATPase channel is working. Magnesium helps this channel work. So if you don’t have enough magnesium, you can do whatever you want but the Na-K-ATPase pump isn’t going to properly. At the same time the intracellular concentration of potassium is going to remain low. Why exactly? It is not described. Quite frustrating really.
My postulation is that the cells are so hungry for potassium that they do get some potassium into the cell via the Na-K-ATPase pump, but that same amount is being excreted. Therefore, continuing to deplete the plasma concentrations that you and I measure. From the same cells, potassium excretion from the cell into the urine happens via the ROMK pump. Magnesium helps limit potassium excretion into the urine by controlling the ROMK pump.
I hope this helps you understand why you need to correct the magnesium when a patient has hypomagnesemia prior to correcting the potassium when they are hypokalemic. This should also answer the question of why replace magnesium before potassium. People have asked if there’s a time factor between magnesium and potassium repletion. I don’t know. Please check out the cited, peer-reviewed journal and don’t trust me. Hat tip to the authors.
-EJ
Learn about serum bicarb on labs and ABG here.
Listen to this on my podcast or YouTube!
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— Tony Breu (@tony_breu) November 2, 2018
Why do we need to correct hypomagnesemia in order to correct hypokalemia?
This thread is for all the interns out there, repleting, and repleting, and repleting…
Citation:
Huang CL, Kuo E. Mechanism of hypokalemia in magnesium deficiency. J Am Soc Nephrol. 2007 Oct;18(10):2649-52. doi: 10.1681/ASN.2007070792. Epub 2007 Sep 5. PMID: 17804670.
Link to PDF
Link to Abstract
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