Hypomagnesemia

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Introduction0:00–0:21

With hypomagnesemia, ‘hypo-’ means ‘lower’ and ‘-magnes-’ refers to magnesium, and -emia refers to the blood, so hypomagnesemia means lower than normal magnesium levels in the blood, and symptoms typically develop at a level below 1 mEq/L.

Physiology0:21–1:33

An average adult has about 25 grams of magnesium in their body. About half is stored in the bones, and most of the other half is found within cells.
In fact, magnesium is a really common positively charged ion found within the cell, second only to potassium. A very tiny fraction, roughly 1% of the total magnesium in the body, is in the extracellular space which includes both the intravascular space - the blood vessels and lymphatic vessels, and the interstitial space - the space between cells.
About 20% of the magnesium in the extracellular space, which would be about 0.2% of the total magnesium, is bound to negatively charged proteins like albumin, but the other 80% or 0.8% of the total magnesium, can be filtered into the kidneys.
So inside the kidney, that magnesium gets filtered into the nephron, and about 30% gets reabsorbed at the proximal convoluted tubule, 60% gets reabsorbed in the ascending loop of Henle, and 5% get reabsorbed at the distal convoluted tubule.
And that leaves only 5% to get excreted by the kidneys. Magnesium levels can fall in a few situations.

Pathology1:33–4:15

One scenario is when the nephron fails to reabsorb the magnesium that’s filtered out of the blood, which would mean more would be excreted in the urine instead of kept in the blood.
Magnesium reabsorption is mostly a passive process where the positively charged magnesium ion follows the electrochemical gradient and moves from the positively charged lumen into the cells lining the lumen which usually have a negative charge.
Now, loop and thiazide diuretics can disrupt that process, because they both make the lumen less positively charged, and this diminishes magnesium’s electrochemical gradient and causing more of the ions to stick around in the filtrate and get peed out.
Another sort of similar scenario is a genetic mutation affecting channels that regulate ion flow, which again could change the electrochemical gradient and cause more magnesium to stick around in the lumen and get peed out.
An example of this is Gitelman syndrome, where there’s a mutation in the gene coding for the Na-Cl cotransporters in the distal tubule.
Now, a different mechanism for hypomagnesemia is prolonged malnutrition, and not enough magnesium gets consumed. Alternatively, there may be enough consumed, but not enough absorbed in the gastrointestinal tract, so instead of going into the blood it gets excreted, and this could happen because of interference from medications like proton pump inhibitors or from a bout of diarrhea.
Another cause of hypomagnesemia includes uncontrolled diabetes mellitus, where sometimes there can be increased levels of glucose in the blood.
And this means that there’s also increased glucose filtered into the kidney and nephron, which ends up attracting a lot of water and causes a large volume of urine to flow through the nephrons.
This high flow carries ions like magnesium right through the nephron because the fast flow doesn’t allow enough time for magnesium reabsorption to happen.
Yet another cause is hungry bone syndrome which is when the thyroid or the parathyroid glands are surgically removed, which leads to increased bone formation.
In this case, the osteoblasts, or bone-forming cells, are literally hungry for ions to make more mineralised matrix, and it consumes the magnesium in the blood.
Another one is alcoholism offers a mixed picture, because often these individuals have a poor diet which means there might be low magnesium intake, but in addition, alcohol increases renal excretion of magnesium.

Complications4:15–5:21

Additionally, low magnesium in the blood is commonly associated with low potassium in the blood, or hypokalemia, partly because a lot of the conditions that cause hypomagnesemia, like diarrhea and diuretic therapy, are also responsible for hypokalemia.
It’s also thought that normally magnesium in the cells of the nephron tend to sort of get in the way of potassium channels a little bit, so with less magnesium, potassium is secreted, excreted, and wasted, which can lead to hypokalemia.
Now, severe hypomagnesemia can also lead to low calcium in the blood, or hypocalcemia, since the parathyroid gland needs magnesium in order to release parathyroid hormone, which normally causes osteoclast cells to release calcium from the bones into the blood.
So without magnesium, therefore, there’s impaired release of parathyroid hormone, and it’s also thought that magnesium’s thought to be needed in order to respond to parathyroid hormone as well, And so both of which results in less calcium in the blood.

Symptoms5:21–6:28

Early symptoms of hypomagnesemia, though, are often neuromuscular. This happens because, under normal circumstances, At the neuromuscular junction, there are voltage-gated calcium channels on presynaptic neurons which need to open and let calcium in to cause the neuron to release neurotransmitter and cause muscle contraction.
Magnesium seems to inhibit calcium influx a little bit, which ends up stabilizing the axon. So without magnesium floating around, calcium can enter neurons more easily, and this makes the muscles and nerves more excitable.
This can lead to neuromuscular symptoms like uncontrolled stimulation of nerves, as well as tetany, which is a condition where there are intermittent muscle spasms throughout the body.
These spasms are particularly evident in the muscles of the hands and the forearm, known as Trousseau sign. When the spasms occur in the muscles of facial expression, it’s called Chvostek sign.
Severe hypomagnesemia can even lead to convulsions or seizures, as well as abnormal heart rhythms. Now, diagnosis of hypomagnesemia is usually done by measuring the level of free unbound magnesium in the serum or doing a 24-hour urine collection.

Diagnosis & Treatment6:28–6:55

Treatment here depends on the cause, and if it’s due to inadequate intake, then it can be supplemented orally. In more severe cases magnesium can be given in the form of magnesium sulphate intravenously or intramuscularly.

Review6:55–7:23

Alright, as a quick recap - Hypomagnesemia refers to a decreased free magnesium ion levels in the blood. This can be caused by excessive excretion by the kidneys or inadequate intake of magnesium.
These situations can lead to symptoms once below 1 meq/L, and these symptoms include uncontrolled firing of the neurons leading to muscle spasms or even seizures and cardiac arrhythmias