Magnesium Disorders

hello this is Eric again from Stanford
University and today I’ll be discussing disorders
of magnesium balance. Historically magnesium in human
physiology has been largely ignored in most
clinical circumstances with the exception that everyone seems
to love aggressively repeating it. The reasons we tend to ignore magnesium
disorders is twofold. First, medical science has limited
understanding of magnesium regulation compared to other electrolytes. And
second, we have limited understanding the
significance and frequency of derangements in magnesium balance. However in this video I’ll summarize the extent of what we do
know. Before discussing pathology let me start with an overview of normal
homeostasis. Of the magnesium in the body about 50
percent is stored in the bones and about 50 percent is in the intracellular
space. There’s actually about 1 percent left over, which is in the blood. Of that 1
percent, 20 percent is bound to albumin, 10 percent is complexed to anions like phosphate, and 70 percent is
unbound, which is the biologically active form.
The consequence of the fact that only a tiny fraction the body’s
magnesium is present in the blood is that serum magnesium levels correlate
poorly with total body magnesium content. Let’s
take a look at how magnesium homeostasis is regulated. As with all electrolytes, homeostasis begins the GI tract, where orally consumed magnesium is
absorbed, a process which appears to be dependent upon passive diffusion from the GI lumen, through
the tight junctions between epithelial cells and into the blood. Similar
to calcium and phosphate homeostasis, the bones act as a reservoir for huge
amounts of magnesium. Unlike calcium and phosphate however, the magnesium in the bones is not in a
tightly regulated equilibrium with the blood, and the bones do not happen nearly as
important a role in magnesium balance. Magnesium is freely filtered through the glomeruli of the kidneys, where most is reabsorbed again in the thick ascending limb of the loop of Henle. As with the gut, most magnesium transport in the
kidneys is due to passive diffusion between cells down an electrochemical gradient which
itself is partly generated by reabsorption of sodium and chloride here.
It is also dependent upon a paracellular protein called called
claudin 16, which is a constituent of the tight junction between epithelial cells. Overall, there are no known hormones or enzymes
that directly regulate magnesium balance. That’s not to say there aren’t any. Just
that we don’t understand them yet. However, what regulation we do know about occurs mostly in the renal tubule where a number of metabolic derangements affect magnesium reabsorption.
Derrangements which prevent reabsorption, and thus lead to hypomagnesemia include low potassium, high calcium, high magneseium (obviously), and a low serum pH. This is a good time to transition to hypomagnesemia. As hypomagnesemia is rarely seen in isolation from other electrolyte abnormalities, it’s difficult to attribute specific symptoms to it. Most symptoms are thought to actually be caused by secondary
abnormalities that are frequently associated with, or even caused by hypomagnesemia. For example, concurrent hypokalemia can lead to cardiac arrhythmias. while concurrent hypercalcemia can lead to
neuromuscular irritability which can manifest as tremors, fasciculations, and tetany. Whether hypomagnesemia in isolation can cause these problems as well is actually not
entirely clear. In addition, there are some
epidemiological studies that suggest a link between chronic hypomagnesemia and both hypertension and coronary
artery disease, though a casual relationship has not yet been clearly established. In a similar manner, despite occasional claims to the contrary there are probably no specific abnormalities of the waveforms on the EKG that are specifically suggestive of hypomagnesemia. However, there are conditions in which hypomagnesemia is associated with an increase risk of
ventricular arrhythmias. These include acute myocardial
infarction, prolonged QT syndrome, congestive heart failure, and digoxin toxicity. lHypomagnesemia also increases the
risk of a-fib following bypass surgery, and may also increase the risk of a-fib
in the general population. Somewhat surprisingly, routine depletion of
magnesium post-CABG has not consistently been found to be
beneficial. There are a large number of causes of hypomagnesemia. The first general mechanism is decreased
GI uptake. This obviously can be due to just poor
dietary intake, most commonly seen alcoholics. It is also
observed in patients on PPIs through an unknown mechanism, or more appropriately through a not
completely understood mechanism. There’s also a very rare disorder called
primary familial hypomagnesemia, the specific genetics at
which are not yet fully worked-out but which presents in infancy as hypocalcemia that’s responsive to IV magnesium therapy. This secondary hypocalcemia is believed
to be due to the effect of hypomagnesemia lowering PTH secretion and increasing PTH
resistance. This effect is explained in a little more
detail in my video on normal calcium and phosphate physiology. Magnesium is also present in
proximal GI secretions, which normally are largely reabsorbed
later on in the GI tract. However, in patients with chronic
diarrhea and malabsorption, and those with extensive inflammatory
bowel disease. this reabsorption can be reduced to the extent causing deficiency. By far, the most varied general category
of etiologies is renal losses. Renal losses can be from
medications, most often loop and thiazide diuretics, but also amphotericin B, aminoglycosides, cisplatin, and calcineurin inhibitors
are all classic causes of hypomagnesemia. As mentioned earlier, hypercalcemia and hyperkalemia both inhibit magnesium reabsorption in the renal tubules. Any process that causes a prominent osmotic diuresis may disrupt the electrochemical gradient
driving magnesium reabsorption which can be seen in uncontrolled
diabetes and during a post obstructive diuresis. Alcohol is thought to cause transient
tubular dysfunction, which contributes to the nearly
ubiquitous hypomagnesemia seen in severe alcoholics. Finally, there are a handful of rare
familial renal magnesium wasting syndromes. The most widely known is Gitelman
syndrome – an autosomal recessive disease caused by a defect in the thiazide-sensitive sodium chloride co transporter in the distal tubule, which also results in hypokalemia and a metabolic alkalosis from
secondary hyperaldosteronism. There are also a number of very rare genetic defects affecting
the claudin 16 protein which lead to a syndrome of
hypomagnesemia, hypercalciuria, and nephrolithiasis. Lastly, in the miscellaneous category is
pancreatitis, where magnesium and calcium salts can be
involved in the saponification of retroperitoneal fat. And magnesium can
be quickly drawn up from the serum in the hungry bone syndrome, described in
a little more detail in my video on hypophosphatemia. Moving on to the diagnostic evaluation
of hypomagnesemia, it’s actually pretty easy as the
etiology is usually evident from the patient’s history. However, if it’s not, one can calculate the
fractional excretion of magnesium. This is calculated as the
product of the urine mag concentration and the plasma creatinine divided by 0.7 times the plasma mag times the urine creatinine. This is all then multiplied by 100 percent. The 0.7 term here accounts for the fact
that only about 70 percent of circulating magnesium is free and is able to be filtered across the
glomerulus. If the fractional excretion of mag is
greater than 2 percent, it suggest excessive renal losses. If it’s less than
2 percent, it suggests GI losses. This calculation is rarely done in
routine clinical practice. When it comes to the treatment of hypomagnesemia, on one level, it’s simple – just give back magnesium. On another level though, it can be a
little tricky if one doesn’t think hard enough about the situation. One reason for this is abrupt increases
in serum mag, as seen during IV administration, inhibit mag reabsorption and lead to transient
mag wasting, which is obviously counterproductive. Therefore, in the absence of symptoms,
arrhythmias, or concurrent hypokalemia, which greatly predisposes to arrhythmias,
oral repletion is usually preferred. On the other hand, if any of those are
present IV mag can be given, usually 1-2 grams
of magnesium sulfate at a time. Although it’s a common practice to give
IV mag relatively quickly, that is, over less than 15 minutes per
gram, this speed is usually not necessary and may even be undesirable. A practical question that quickly comes
up and which is literally never mentioned in the literature, is
what should the goal magnesium level be when undertaking repletion. In the US at
least, it’s common practice to replete serum mag
to high normal levels, that is, greater than 2.0 milligrams per
deciliter. This practice is not based on strong
evidence or guidelines, and is probably not necessary for most
patients. Possible exceptions to this, that is,
patients to still replete above 2 include those with acute MIs, those with active arrhythmias, and those with long QT syndrome. And please remember that one of the most
common causes of hypermagnesemia is iatrogenic excessive repletion in patients who are either elderly
and/or have renal impairment, so therefore, please be careful with both
the total dose and the rate of repletion in these
patients. Let me down move onto hypermagnesemia. I feel like because hypermagnesemia is often more abrupt and iatrogenic, its easier to demonstrate that some
findings are truly due to hypermagnesemia, and not from other concurrent
electrolyte disorders as with hypomagnesemia. These clinical manifestations fall into two main categories: cardiovascular manifestations include
bradycardia and conduction block, which can progress to complete heart
block and even asystole, along with hypotension. The other category is neuromuscular
findings which include decreased reflexes, muscle weakness, drowsiness progressing
to coma, and signs of parasympathetic blockade. These signs include cutaneous flushing, dry
mouth, dilated pupils, and urinary retention. The etiologies of hypermagnesemia are
pretty minimal. First is renal failure. The kidneys are the
only known place in the body where magnesium levels are sort of regulated, and if they aren’t
working properly, there is no way for the body to get rid
of excessive magnesium that it may have absorbed from the gut. The
next mechanism of hypermagnesemia is simply excessive mag administration. This can be in the form of massive PO
intake from the laxative magnesium citrate or from epsom salts. It can be from excessive IV infusion,
which can be seen during the treatment of the life-threatening obstetric
condition of eclampsia, in which appropriate treatment almost
always results in supernormal magnesium levels. And finally, can be from magnesium containing enemas, particularly when used in a patient with
concurrent renal impairment. And in fact, magnesium containing
enemas are contraindicated in that situation. The only significant miscellaneous
mechanism is tumor lysis syndrome, in which a very large number of cancer
cells either spontaneously or in response to initiation of
chemotherapy, suddenly die and break apart releasing a large amount
of intracellular magnesium and in fact all their internal contents. In general, the hypermagnesemia from
this will be relatively minor issue as compared to the hyperkalemia. The diagnostic evaluation of hypermagnesemia is the easiest of all electrolyte abnormalities as the
etiology is almost always evident from history and
review renal function. I personally have never encountered a
patient with hypermagnesemia who required any diagnostic evaluation
beyond cursory chart review. The treatment of hypermagnesemia depends upon the patient’s renal function. If it’s normal, the typical treatment is
simply to stop the causative magnesium containing medication. If the patient has chronic kidney
disease with a GFR on the order a 15 to 45, or has non-anuric acute kidney injury, a combination of normal saline and furosemide should be sufficient, with solid attention given to maintaining
appropriate volume status. If the patient has chronic kidney
disease with a GFR under 15 or has anuric kidney injury, the
only way to get rid of the excess mag will be dialysis. Finally, in a setting of acute,
life-threatening hypermagnesemia, IV calcium may temporarily antagonize
activity of the excessive mag. It’s possible that in another 10 or 20
years, we’ll know a lot more about this electrolyte
but from a clinical standpoint, that’s all there is to say about it right
now. If you found this video interseting and useful, you may want to check out my similar
videos on calcium and phosphate disorders. or upcoming videos on sodium and
potassium disorders

51 thoughts on “Magnesium Disorders

  1. Yes, that is where I found this too: YouTube Australia's top educational result. For years I heard about lack of magnesium could be causing my muscle tightness and headaches, so it took my interest. Thanks for the info. 

  2. Thanks for the info Patrick, "your mum", and Lou…  So part of the mystery's been solved – apparently the video was picked out by an automated YouTube algorithm to be a featured video on the main education channel in the US, Australia, and UK (maybe others as well).  While I certainly appreciate the attention, extra views, and subscribers that it's driving, I'm not sure this particular video of my strongest or one with a particularly broad public appeal.  Please consider checking out my other videos on my main channel page, including the top 10 playlist.  Thanks everyone!

  3. In my opinion, you should explore the role that magnesium has in birth. This situation provides a very clear physiological response pattern to magnesium.

  4. I've had dangerously low levels of potassium and magnesium most of my life, I've also had UC since I was 6. I started having chronic kidney stones at 19. Although many of my friends who have UC also have had chronic Calcium kidney stones the Doc's say it's not related. Perhaps the low absorption of magnesium and potassium from UC is also causing an access of calcium?

  5. Because the thyroid plays a large part in calcium regulation, and because hypermagnesemia presents similarly to hypercalcemia, wouldn't one look to the thyroid/parathyroid as a player in Mg regulation?

  6. I've had paroxysmal a-fib for ten years and obviously electrolyte balance is important in maintaining sinus rhythm in my case. Blood Mg levels are a poor indicator of intracellular Mg levels; rather a cheek cell test will give a more accurate intracellular level, indicative of that in the heart myocytes. Since Mg supplementation so often causes diarrhoea, or at least the potential for a "shart" (always a danger at my age, lol) I find chelated Mg supplements to be way more effective in getting the balance right without side (or should that be bottom?) effects of other forms of Mg supplements. Oh, and a seemingly healthy diet in Australia sometimes can have low Mg content, due to our poor soils.

  7. Helped me to understand why most of the people I know who take high blood pressure meds are ending up on dialysis. Physicians are not checking their patients who are on meds for years at a time.

  8. @Ines Cruz (sorry YouTube is not letting me directly link to your comments): While I can't offer you specific, individualized medical advice on here, I will say that it is not standard of care in the US for a physician to prescribe an electrolyte supplement without first checking the serum chemistries.  While serum magnesium does not correlate well with total body magnesium stores, supplemental magnesium should be used very cautiously if significant renal dysfunction were also present.  Also, palpitations related to electrolyte deficiencies could easily be from potassium depletion – though both low magnesium and low potassium only cause palpitations via their possible contribution to abnormal heart rhythms – specifically atrial fibrillation, ventricular tachycardia, and multifocal atrial tachycardia (the last of which is very uncommon).  

  9. I'm amazed at your finding of magnesium I have a ruptured discs L4 and L5 and magnesium and B12 have been my best pain Killers if this information helps you please use it and pass it on I've manged without surgery but plenty of therapy thank you for your findings I was worried of any future side effects of magnesium, but with this information I can see I can over due it I'll value now more my yearly (Medical) physical

  10. I realize that not every video will appeal to every viewer, but this one has been getting an usually large number of negative votes since it was featured on YouTube's education channel.  If you are considering giving it a down vote, can you please let me know why?  Please realize that these videos are meant for medical professional and students; if I had the ability to remove it from the YouTube's general education channel, I would!

  11. My attending pimped me on this subject a couple of days ago and I couldn't find much information on the it at all. I did see your video on YouTube's education channel and decided to venture a view. I'm glad I did! Thanks for an easy understanding of Magnesium's role in the body!

  12. Anyone having passed a high school biology class should be able to follow most of this lecture.  What's so difficult about this?  If there are terms you don't understand, google them!  Educational videos are for learning, not for pure entertainment.

  13. I'm here listening and I like what
    I'm hearing. I even had to check
    my bottle of #centrumsilver to
    see if I was getting #magnesium
    and yes, 50 mg at 13%. Thanks
    for this lecture.

  14. Your video is educational and reminds me of biology class I have the urge to take notes and make diagrams. I really enjoyed your lecture.

  15. Excellent video. I really appreciate the information you provided. Thank you for making it available to the general public. 🙂

  16. hi eric, please dont remove this video, i see there are no like/dislike numbers…
    im hoping you can clear up the serum mag test, rbc mag test, mag loading test, and any other lab tests to evaluate magnesium, there is a lot on the web about having the active/rcbmag test done,..there is a great deal of information by carolyne dean i was wondering if you are familiar with her work, also i appreciate being clear in the clarification of the limits of clinical use of magnesium in standard care and evaluation, it is important to make the distinction between what is known and what is used in regular medical care, as usual there is a great discrepancy gap….

  17. ah, i think it would be great if you would address the role magnesium plays in enzymatic reactions, ie pth, calcidiol, calcitriol …. (of course every enzymatic rx needs a vit and a mineral,.. so it is a very large topic) in addition dr osborne has a good short magnesium overview: Signs and Symptoms of Magnesium Deficiency

  18. Very educated video! Thanks for uploading them.
    My 10 year old son was diagonosed with Gitelman's Syndrome 2 years ago and ever since he takes Mg oxide and Potassium supplements every day. What is the ideal Mg level for his age. I know the norm is >2.0 mg accordingly to USA. What is the lower threshold which can be harmful? It is a challenge to maintain his Mg and K levels. Do you recommend any alternatives for better absorption of these minerals. I heard Dermal Mg oil,epsom salts etc, will they help to store Mg or it does not matter as Kidney will not re-absord them ?
    Thanks again!

  19. Hei, dear Eric,
    Don't remove your videos! Though I have been working as a physician for more than ten years. I still found your videos are very very helpful. Thank you for your hard efforts and your wonderful jobs!

  20. can you provide your references for the guidelines you mentioned in this video regarding the repletion of Mg etc

  21. Hi,
    Thank you for video! I've learned that hyperglycemia would cause the intracellular movement of magnesium but I cannot understand how it works in the systems. Would you please provide some guidance here? Thank you so much!

  22. My Gi tract does not take kindly to Mag of any type, so, I use spray on mag oil from mag chloride and mag sulfate from ES.
    Is there any likelihood of hyper mag from this method of application on a daily basis.
    sleep patterns are greatly improved with my application of mag to date.
    cheers and thanks, great learning with your style and presentation.

  23. Thank you for this interesting and informative video. i have two suggestions and one question,

    – you didn;t cover transdermal Mg absorbtion (Mg chloride also known as Mg Oil)

    = Mg serum levels are a very poor indicator of overall Mg levels

    – source on the Mg and loop of Henle please?

  24. I initially thought the 15mins were going to be long. Every minute of it was useful and filled with important information needed for me (pharmacy student), probably not for laymen. Thank you so much 🙂

  25. This video is fantastically and educationally informative. If it has been getting an unusually large number of thumb down, it is due to its very technical language which may not go down with some large numbers of YouTube viewers. The content is, even, hard for medical students to take in, never mind the average viewer wanting to know some simple facts about Magnesium Disorder. I have A GP friend 56 years old, we both watched this video together and she was taken in by the depth of its medical analysis. Good luck and thank for this highly informative and well presented video.

  26. Excellent video and very informative . Got 2 full pages of notes and will be doing some further study with the GI correlation in acute and chronic GI issues. Magnesium is the most underrated and least discussed electrolyte and needs more attention. Lots of people I am hearing are taking massive amounts PO for muscle pain and I fight to inform them only to take if a doctor reccomends it. Thank you again, will be subscribing and investing more time watching your videos and look forward to learning more!

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