Introduction: Hypomagnesemia has two major mechanisms, loss of the gastrointestinal tract or kidney loss. Whatever the cause, hypomagnesemia requires only a relatively mild magnesium deficiency, as extracellular magnesium can hardly be exchanged quickly with much larger reserves of bone and cellular magnesium. Hypomagnesemia is usually accompanied by hypokalemia, which is due to loss of potassium in the urine and decreased parathyroid hormone (PTH) secretion and end-organ resistance to PTH.
First, hypomagnesemia has two major pathogenesis, magnesium ions are lost through the gastrointestinal tract or kidneys
1. Gastrointestinal loss
Gastrointestinal secretions contain part of the magnesium, and the potential loss persists and is unregulated. There is not much necessary loss, but progressive magnesium loss occurs when the diet is significantly deficient in magnesium.
Magnesium loss in both the upper and lower gastrointestinal tracts can lead to hypomagnesemia. In general, diarrhea is more likely to cause magnesium loss than vomiting. Because the magnesium content of lower gastrointestinal secretions (up to 15mEq/L) is much higher than that of the upper gastrointestinal tract (about 1mEq/L). Common conditions that may cause hypomagnesemia include acute and chronic diarrhea, malabsorption and steatorrhea, and small bowel bypass surgery.
In addition, hypomagnesemia with secondary hypocalcemia can be caused by familial disorders (primary intestinal hypomagnesemia) characterized by selective magnesium malabsorption. This disorder causes hypocalcemia in the neonatal period and can be relieved by magnesium supplementation. X-linked recessive inheritance appears to exist in some patients, but some studies have proposed autosomal recessive inheritance linked to chromosome 9.
2. Kidney loss
(1) Hypercalcemia
ROMK inhibition inhibits sodium chloride reabsorption in the coarse section of the Henri loop ascendant branch, as well as reduces the paracellular reabsorption of magnesium and calcium. Stimulation of CaSR leading to the occurrence of ROCK suppression in this renal unit segment is the mechanism of V. Bartter syndrome. Thus, hypercalcemia can produce a Bart-like phenotype. In addition, stimulation of CaSR can reduce the calcium-magnesium permeability of the rough-segment paracellular pathway of the Henri loop, which may be due to increased expression of sealed protein-14, which can negatively regulate sealed protein-16 and sealed protein-19.
(2) Other acquired tubular dysfunction
Tubular dysfunction can also cause magnesium loss during recovery from acute tubular necrosis, after kidney transplantation, or during diuresis after de-obstruction.
(3) Familial renal magnesium loss
Primary renal magnesium loss is uncommon and can be sporadic or familial. There are several different types. Primary renal magnesium loss is an exclusionary diagnosis. The basis is that there is no other obvious cause and that the amount of urine magnesium excreted is too high.
(4) Gitelman syndrome and Bartter syndrome
Gitelman syndrome is the most common familial loss of renal magnesium, usually with salt loss, hypokalemia metabolic alkalosis, and hypocalciuria. The cause is a latent mutation in the gene encoding the thiazide-sensitive sodium chloride synergistic transporter (SLC12A3). Although hypokalemia in the syndrome is usually attributed to decreased sodium chloride transport, the direct effects of hypomagnesemia may also be predominant. Hypomagnesemia in Gitelman syndrome is significantly more severe than hypomagnesemia caused by thiazides. Patients with Bartter syndrome may also develop hypomagnesemia due to Henri loop ascending branch coarse-segment resorption disorder, particularly late-onset Bartter syndrome caused by mutations in the CLCNKB gene, which is similar to Gilelman's syndrome Type 3 Bartter syndrome.
Second, what are the symptoms of hypomagnesemia patients? Patients with hypomagnesemia are often associated with hypokalemia
1. Magnesium deficiency with normal blood magnesium
A small number of patients with hypocalcemia have been reported to respond to magnesium therapy when hypomagnesemia is not detected. Most of these patients will have other manifestations suggestive of magnesium deficiency, such as alcoholism or diarrhea. For example, a prospective study included 82 patients admitted to hospital for alcohol-related disorders, of whom 30 had unexplained hypocalcemia (8 mg/dL or 2 mmol/L), 14 had hypomagnesemia, and 16 had normal plasma magnesium concentrations. However, intranuclear magnesium concentrations were lower in both hypocalcemia groups, which was also seen in normal serum calcium. After 3-5 days of treatment with elemental magnesium 32-64mEq/d, plasma calcium concentrations in both groups returned to normal.
2. Hypokalemia
Patients with hypomagnesemia are often associated with hypokalemia, which occurs in 40% to 60% of cases. This association is partly attributed to underlying conditions that cause both magnesium and potassium loss, such as diarrhea and diuretic therapy. Evidence of renal potassium depletion is also present in patients with hypomagnesemia, due to increased potassium secretion in the renal junction tubules and cortical aggregate ducts. The following sequence of events may explain how the situation occurred.
Renal junction tubules and cortical aggregate duct cells secrete potassium from the cell into the lumen, a process mediated by luminal potassium (ROMK) channels and inhibited by intracellular magnesium. Hypomagnesemia causes a decrease in intracellular magnesium concentration, thereby reducing the inhibitory effect on potassium ion outflow. Given the very high intracellular potassium concentration, this change will prompt potassium to be secreted from the cell into the lumen of the tube, thereby increasing potassium loss in the urine. In this setting, potassium supplementation therapy is relatively difficult to correct hypokalemia, so magnesium deficiency needs to be corrected.
Third, oral magnesium salts can alleviate the patient's condition, for severe hypomagnesemia or inability to tolerate oral magnesium salts, intravenous or intramuscular magnesium sulfate can be administered
1. Oral administration
Magnesium salts can be used when hypomagnesemia is symptomatic or when blood magnesium concentrations persist < 1.25 mg/dL (<0.50 mmol/L). Patients with alcoholism generally receive empiric treatment. In these patients, magnesium deficiency may be about 12 to 24 mg/kg.
If renal function is normal, twice the estimated magnesium deficiency should be given, as about 50% of the supplemented magnesium is excreted in the urine. Oral magnesium salts (eg, magnesium gluconate 500 to 1000 mg po tid) for three to four days. Oral magnesium supplementation is generally difficult to tolerate and often leads to diarrhea.
2. Parenteral administration
Patients with severe illness, symptomatic, and difficult to tolerate oral magnesium supplementation require parenteral administration. Sometimes a single injection is given to alcoholics who cannot continue oral therapy. If magnesium supplementation through the parenteral route is necessary, it can be injected intravenously in 10% magnesium sulfate (MgSO4) solution (1 g/10 mL) or intramuscularly with 50% solution (1 g/2 mL). Blood magnesium should be measured frequently during magnesium supplementation, particularly through the parenteral route or if the patient has renal insufficiency. In these patients, treatment continues until the blood magnesium returns to normal.
Conclusion: Gastrointestinal secretions contain part of magnesium. Not much is necessarily lost, but a pronounced dietary deficiency can lead to progressive magnesium loss. Magnesium loss in the upper and lower gastrointestinal tracts can induce hypomagnesemia. Common conditions that may cause hypomagnesemia include acute and chronic diarrhea, malabsorption, and steatic diarrhea and small bowel bypass surgery. Acute pancreatitis may also cause hypomagnesemia.