USMLE® Step 1 style questions USMLE
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A 20-year-old man comes to the clinic because of muscle cramps and fatigue for the past year. He has experienced muscle cramps his entire life, but they have now become more frequent and painful. He has always awoken several times per night to urinate. His medical history includes chronic mild hypokalemia and hypomagnesemia. Family history is significant for similar symptoms in one of his four older sisters. He takes no medications. His temperature is 37.0°C (98.6°F), pulse is 76/min, respirations are 14/min, and blood pressure is 126/78 mm Hg. Physical examination shows a tired-appearing male with no other abnormalities. In addition to his chronic electrolyte deficits, laboratory studies show a mild metabolic alkalosis. Which of the following is the most likely diagnosis?
Content Reviewers:Rishi Desai, MD, MPH
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.
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. 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.
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.
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.
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