Hypomagnesemia Flashcards
Clinical Manifestations of Hypomagnesemia
Signs/symptoms (typically <1.2 mg/dL): Muscular tremors, fasciculations, nystagmus, tetany, altered mentation, depression, psychosis, migraine, ataxia, vertigo, seizures, dysphagia, asthma, chronic fatigue syndrome.
Clinical Manifestations of Hypomagnesemia
Electrolyte disturbances associated with hypomagnesemia: Hypokalemia: thought to be due to hypomagnesemia induced hyperaldosteronism and impaired Na+-K+-ATPase at the DCT and ROMK at TAL (Mg2+ is a cofactor for the former and negative regulator for the latter—i.e., Mg2+ keeps ROMK closed. The lack of Mg2+ leads to K+ leakage via ROMK). Hypocalcemia: impaired PTH secretion and tissue sensitivity to PTH
Clinical Manifestations of Hypomagnesemia
ECG changes: Prolonged QT and PR intervals Flattening or inversion of precordial P waves ST-depression T-wave inversion Widening of QRS Torsades de pointes Treatment-resistant ventricular fibrillation (and other arrhythmias) Worsening of digitalis toxicity
Clinical Manifestations of Hypomagnesemia
Other associated adverse effects: altered glucose homeostasis, increased insulin resistance, atherosclerotic vascular disease, hypertension, myocardial infarction, osteoporosis, worse GFR decline in patients with diabetes type 2 and CKD, worse recovery potential in AKI in ICU setting, asthma, osteoporosis.
Clinical Manifestations of Hypomagnesemia
The protective effects of magnesium is thought to be via its anticalcification property, antioxidant activity on endothelial function, and mesangial smooth muscle relaxation effect among others.
Clinical Manifestations of Hypomagnesemia
Decreased intake: malnutrition, prolonged intravenous therapy without Mg2+ supplementation Decreased intestinal absorption: surgical resection of small intestine, familial Mg2+ malabsorption (TRPM6)
Clinical Manifestations of Hypomagnesemia
Excessive fluid loss: prolonged nasogastric suction, ulcerative colitis, laxative abuse, intestinal and biliary fistulas.
Clinical Manifestations of Hypomagnesemia
Excessive urinary losses: Diuretics, postobstructive, post-transplant diuresis. NOTE: The use of proton pump inhibitors has been reported to be associated with hypomagnesemia in patients receiving concurrent diuretics. Hypercalcemia
Clinical Manifestations of Hypomagnesemia
Excessive urinary losses cont’d: RTA Hypophosphatemia Drugs aminoglycosides, amphotericin, cisplatin >> carboplatin, cyclosporine, EGF receptor inhibitors (e.g., cetuximab, panitumumab, matuzumab), antituberculous drugs (e.g., viomycin, capreomycin), ritodrine, β-adrenergic agonists (e.g., theophylline, salbutamol, riniterol), other drugs (amphotericin B, pentamidine, foscarnet, pamidronate, anascrine).
Clinical Manifestations of Hypomagnesemia
Inherited disorders: Hypomagnesemia with secondary hypocalcemia: autosomal recessive mutation of TRPM6 Mutation affecting pro-EGF processing: normal EGF-binding to its receptor is necessary for normal trafficking of TRPM6 to the apical surface in distal convoluted tubules. Absence of EGF or presence of antibodies directed against the EGF receptor (e.g., cetuximab) can lead to urinary magnesium wasting.
Clinical Manifestations of Hypomagnesemia
Inherited disorders cont’d: Gitelman syndrome Familial hypomagnesemia with hypercalciuria and nephrocalcinosis: Mutation of claudin 16 or 19 (tight junction proteins), autosomal recessive, age of onset: children, renal Mg2+ and Ca2+ wasting, hypomagnesemia but normal serum Ca2+ and K+, nephrolithiasis and nephrocalcinosis.
Clinical Manifestations of Hypomagnesemia
Inherited disorders cont’d: Isolated dominant hypomagnesemia (IDH): Mutation of γ-subunit of Na+-K+-ATPase, autosomal dominant, urine Mg2+ wasting but hypocalciuria. Clinically, affected individuals have hypomagnesemia but normal serum Ca2+ and K+. Hepatic nuclear factor 1-β mutation: HNF1B regulates transcription of FXYD2, a gene encoding γ-subunit of Na+-K+-ATPase; clinically same as IDH.
Clinical Manifestations of Hypomagnesemia
Inherited disorders cont’d: Kv1.1 mutation: reduces K+ exit into lumen, hence reduced positive voltage that would normally favor Mg2+ entry via TRPM6. Kir4.1/5.1: loss of function reduces basolateral K+ recycling, hence reduced 3Na+-2K+-ATPase activity, and favorable negative voltage for Mg2+ apical entry. CaSR activation reduces Kir4.1 expression.
Clinical Manifestations of Hypomagnesemia
Others: acute pancreatitis, transfusion of citrated blood, severe burns, continuous ambulatory peritoneal dialysis, chronic alcoholism (multifactorial)
Diagnosis of Hypomagnesemia:
Evaluation Indices
Total magnesium urinary loss in hypomagnesium:
Urinary magnesium > 20 mg/d indicates urinary Mg2+ wasting.
Urinary magnesium < 10 mg/d indicates total body Mg2+ depletion.
Diagnosis of Hypomagnesemia:
Urinary Mg excretion may be measured as fractional excretion of Mg (FeMg) = [(urine Mg × SCr)/(0.7 × serum Mg × urine Cr)] × 100
Factor of 0.7 indicates only ~70% of plasma Mg is filterable.
Equation should only be used with relatively good kidney function.
FeMg > 2% to 4% indicates excessive renal Mg loss.
FeMg < 2% to 2.5% indicates nonrenal Mg loss.
Diagnosis of Hypomagnesemia:
For GI causes of magnesium, 24-hour urine magnesium < 20 mg
For renal magnesium loss, 24 hour urine magnesium > 20 mg
Conditions involving defective magnesium reabsorption at the loop of Henle will have concurrent calcium wasting, that is, urinary calcium > 250 mg/d. Examples: loop diuretics, CaSR agonists (e.g., gentamicin, cinacalcet), familial hypomagnesemia with hypercalcemia and nephrocalcinosis (claudin 16/19 mutations)
Diagnosis of Hypomagnesemia:
Conditions involving defective magnesium reabsorption at the distal tubules will have hypocalciuria, that is, urinary calcium < 200 mg/d. Examples: thiazides, Gitelman syndrome, IDH.
Management of Hypomagnesemia:
Severe deficiency: Intravenous repletion for severe but non–life-threatening hypomagnesemia: 1 to 2 g/h for 3 to 6 hours then 0.5 to 1 g/h as needed to correct deficiency
Symptomatic deficiency: Intravenous: 1 to 2 g over 15 to 60 minutes; maintenance intravenous therapy may be required to correct deficiency (0.5 to 1 g/h).
Management of Hypomagnesemia:
Severe or symptomatic
1 to 2 g MgSO4 (in 100 mL 5% dextrose water) intravenously over 15 minutes
Torsades: 1 to 2 g MgSO4 intravenously over 1 to 2 minutes
Seizures: 2 g MgSO4 intravenously over 10 minutes; administration of calcium may be necessary.
Management of Hypomagnesemia:
NOTE
Intravenous magnesium supplementation causes an abrupt rise in serum Mg2+ level which leads to reduced reabsorption of Mg2+ across the thick ascending limb of the loop of Henle. This limits efficient magnesium repletion with intravenous supplementation.
Management of Hypomagnesemia:
Aldosterone has been suggested to induce renal Mg2+ wasting, an effect that may be ameliorated by aldosterone antagonists (spironolactone, eplerenone).
