Mechanism of Hypokalemia in Magnesium Deficiency

UT Southwestern Medical Center, Department of Medicine, 5323 Harry Hines Boulevard, Dallas, TX 75390-8856, USA.
Journal of the American Society of Nephrology (Impact Factor: 9.34). 11/2007; 18(10):2649-52. DOI: 10.1681/ASN.2007070792
Source: PubMed


Magnesium deficiency is frequently associated with hypokalemia. Concomitant magnesium deficiency aggravates hypokalemia and renders it refractory to treatment by potassium. Herein is reviewed literature suggesting that magnesium deficiency exacerbates potassium wasting by increasing distal potassium secretion. A decrease in intracellular magnesium, caused by magnesium deficiency, releases the magnesium-mediated inhibition of ROMK channels and increases potassium secretion. Magnesium deficiency alone, however, does not necessarily cause hypokalemia. An increase in distal sodium delivery or elevated aldosterone levels may be required for exacerbating potassium wasting in magnesium deficiency.

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    • "a reduction in inhibitory effects on renal ATP-dependent ROMK channels, increasing basal potassium excretion [19] "
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    ABSTRACT: Objective. To present an unusual but known cause of hypomagnesaemia induced-hypocalcaemia in a chronic GORD patient with severe symptoms with a review of the current literature. Methods. Analysis of the clinical and laboratory findings of the patient and discussion of the multi-factorial nature of his disease and the underlying mechanisms. Results. Our patient described features of magnesium deficiency such as weakness, muscle twitches, and fits with clinical signs of hypocalcaemia: a carpal pedal spasm and paraesthesia. Preadmission blood results revealed low calcium and magnesium levels. He was admitted to ITU, when he presented with seizures and developed encephalopathy. The total vitamin D level was 52.4 nmol/L (>49.9). His U&Es and LFTs were within the normal range with the exception of potassium. He was on Omeprazole for his GORD. With omission of the PPI 1 day after admission and replacement therapy, his ion levels normalised. Conclusion. Hypomagnesaemia is often undiagnosed and is associated with multiple biochemical abnormalities. Treatment focus should be aimed at stopping the PPI and replacing the magnesium. Over use of PPIs is a problem in practice, with the FDA issuing a warning over long-term use. Continued monitoring and decision making on dose reduction/withdrawal is essential to avoid complications.
    11/2012; 2012:632721. DOI:10.1155/2012/632721
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    • "This effect on the channels could play a role in preventing urinary K losses when K intake is low, as reduced luminal K + concentrations observed under these circumstances would increase the affinity for Mg 2+ (Yang et al., 2010). In addition , this interaction could help explain the difficulty in maintaining plasma K + concentrations in patients with hypomagnesemia (Huang and Kuo, 2007). Thus, channel block by internal cations, especially Mg 2+ , has potential physiological and pathophysiological relevance. "
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    ABSTRACT: We investigated the effects of changing extracellular K(+) concentrations on block of the weak inward-rectifier K(+) channel Kir1.1b (ROMK2) by the three intracellular cations Mg(2+), Na(+), and TEA(+). Single-channel currents were monitored in inside-out patches made from Xenopus laevis oocytes expressing the channels. With 110 mM K(+) in the inside (cytoplasmic) solution and 11 mM K(+) in the outside (extracellular) solution, these three cations blocked K(+) currents with a range of apparent affinities (K(i) (0) = 1.6 mM for Mg(2+), 160 mM for Na(+), and 1.8 mM for TEA(+)) but with similar voltage dependence (zδ = 0.58 for Mg(2+), 0.71 for Na(+), and 0.61 for TEA(+)) despite having different valences. When external K(+) was increased to 110 mM, the apparent affinity of all three blockers was decreased approximately threefold with no significant change in the voltage dependence of block. The possibility that the transmembrane cavity is the site of block was explored by making mutations at the N152 residue, a position previously shown to affect rectification in Kir channels. N152D increased the affinity for block by Mg(2+) but not for Na(+) or TEA(+). In contrast, the N152Y mutation increased the affinity for block by TEA(+) but not for Na(+) or Mg(2+). Replacing the C terminus of the channel with that of the strong inward-rectifier Kir2.1 increased the affinity of block by Mg(2+) but had a small effect on that by Na(+). TEA(+) block was enhanced and had a larger voltage dependence. We used an eight-state kinetic model to simulate these results. The effects of voltage and external K(+) could be explained by a model in which the blockers occupy a site, presumably in the transmembrane cavity, at a position that is largely unaffected by changes in the electric field. The effects of voltage and extracellular K(+) are explained by shifts in the occupancy of sites within the selectivity filter by K(+) ions.
    The Journal of General Physiology 11/2012; 140(5):529-40. DOI:10.1085/jgp.201210835 · 4.79 Impact Factor
    • "Hypomagnesemia causes hypokalemia via the action on renal outer medullary potassium (ROMK), the inwardly rectifying K channel in the distal nephron, required for the back-leak of K+. A low intracellular Mg2+ increases ROMK efflux activity and thereby K+ wasting.[25] Hypomagnesemia causes hypocalcemia via inappropriately low parathyroid secretion and parathyroid hormone resistance[26] and decreased action of 1,25 hydroxylase. "
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    ABSTRACT: Hypomagnesemia is reported in type 2 diabetes; magnesium deficiency may play a role in the development of endothelial dysfunction and altered insulin function. To assess the incidence of hypomagnesemia among noncritically ill patients of Type 2 diabetes mellitus and to evaluate the relation of hypomagnesemia to glycemic control and various long-term complications of diabetes mellitus. One hundred and fifty, noncritically ill (APACHE score < 10) type 2 diabetes mellitus patients, who were admitted in the Departments of Medicine and Endocrinology, GMCH for uncontrolled hyperglycemia and/or various diabetic complications were studied. Serum magnesium was assessed at admission and rechecked in those found to be deficient. Hypomagnesemia (Se magnesium < 1.6 mg/dl) was documented in 17 (11.33%) patients with a female:male ratio of 9:8. Mean HbA1c was 11.9% in the hypomagnesemic patients compared with 9.8% in controls (P =0.0016). Retinopathy, microalbuminuria, macroalbuminuria, foot ulceration, and neuropathy was present in 64%, 47%, 17.64%, 58.8%, and 82.35%, respectively, of the patients with hypomagnesemia as compared with 45.8% (P =0.118), 38.34% (P =0.704),15.03% (P =0.566), 22.55% (P =0.011) and 82.7% (P =0.976) without hypomagnesemia. Coronary artery disease was less common in the hypomagnesemia group (17.6% vs 39%), but comparable in the subgroup < 50 years (27% vs 25%) (P =0.796). Hypomagnesemia in diabetes was associated with poorer glycemic control, retinopathy, nephropathy, and foot ulcers.
    11/2012; 16(6):1000-3. DOI:10.4103/2230-8210.103020
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