Approach to Hypomagnesemia and Hypokalemia

Chapter 56

Approach to Hypomagnesemia and Hypokalemia


Hypomagnesemia refers to low circulating concentrations of magnesium in the serum and occurs when total magnesium (Mg) concentrations are below 1.89 mg/dl in dogs and below 1.75 mg/dl in cats; ionized hypomagnesemia occurs when serum ionized Mg concentrations are below 0.43 mmol/L in both species. These values may vary slightly depending on the reference laboratory used. In veterinary medicine, hypomagnesemia is one of the most common electrolyte abnormalities detected in critically ill patients. In 48 dogs admitted to a veterinary teaching hospital intensive care unit, the incidence of hypomagnesemia at admission was 54%, and hypomagnesemic dogs had a higher incidence of concurrent hypokalemia and hyponatremia, as well as a longer length of hospitalization, compared with normomagnesemic counterparts (Martin et al, 1994). A prospective study of 57 cats admitted to an intensive care unit reported that hypomagnesemia developed in 28% during hospitalization (Toll et al, 2002); another study reported an incidence of hypomagnesemia of 62% and 57% in cats with diabetes mellitus and diabetic ketoacidosis, respectively (Norris, Nelson, and Christopher, 1999). Its high frequency of occurrence and impact on morbidity in veterinary patients have established hypomagnesemia as one of the most clinically significant electrolyte disorders in critically ill animals.

Physiologic Role and Function

Mg plays a pivotal role in many physiologic processes. One of its main contributions is serving as an essential cofactor and catalyst in over 300 intracellular enzymatic reactions, which makes it vital in regulating (1) synthesis and metabolism of carbohydrates, lipids, and proteins; (2) synthesis, degradation, and stabilization of nucleic acids; (3) oxidative phosphorylation and anaerobic glycolysis; (4) neuromuscular activity, cardiac conduction, and excitability; (5) signal transduction; (6) intracellular potassium (K) and cytoplasmic calcium concentrations; and (7) immunologic function. Of greatest importance, Mg complexes with and stabilizes many polyphosphate compounds and therefore plays a vital role in facilitating most cellular phosphorylation reactions. For example, every molecule of adenosine triphosphate (ATP) must complex with Mg to be biologically active.

Distribution and Homeostasis

Mg is the second most abundant intracellular cation (second to K) and the most abundant free divalent cation in the body. Ninety-nine percent of total body Mg content is found intracellularly, with approximately 60% to 85% located in bone complexed with calcium and phosphorus. The remainder of intracellular Mg is located primarily within skeletal muscle and to a smaller degree within the liver, heart, and other soft tissues. Less than 1% of total body Mg content is located extracellularly in the serum. Approximately 60% to 70% of serum Mg is unbound or ionized and freely filterable across the glomerular filtration barrier, while the remainder is either bound to protein (primarily albumin) or complexed with anions such as phosphate, citrate, sulfate, lactate, or bicarbonate. The ionized portion is available for cellular use and physiologic processes and is therefore considered the biologically active portion.

The kidneys serve as the major regulatory organ for Mg homeostasis through glomerular filtration and tubular reabsorption. Secondary to the kidneys is the intestinal tract. The ileum followed by the jejunum and colon are responsible for most of the absorption. The amount of dietary Mg intake, along with the degree of complex formation or chelation of Mg within the intestinal lumen, influences absorption. During low dietary intake of Mg, intestinal absorption may be as high as 70%, compared with only 25% during periods of high dietary intake. Only ionized Mg is absorbed across the intestinal barriers; therefore any increase in complex formation or chelation of Mg reduces absorption.


The three causes of Mg deficiency are (1) decreased intake, (2) alterations in compartmental and cellular distribution, and (3) increased loss (Box 56-1). Realistically, hypomagnesemia results not from any one of these mechanisms but rather from a combination of all three. Poor dietary Mg intake does not usually cause clinically significant hypomagnesemia; however, chronic dietary Mg deficiency may lead to a significant depletion of body stores. Administration of Mg-deficient intravenous fluids or parenteral nutrition may also result in hypomagnesemia in hospitalized animals.

Cellular translocation, chelation, and sequestration account for redistribution of Mg between body compartments. Cellular translocation involves shifting from extracellular space to intracellular space, a result of catecholamine and insulin release as well as administration of amino acids. Disease states involving massive catecholamine release (e.g., sepsis, trauma, shock) can stimulate release of free fatty acids that chelate Mg. Massive transfusions can result in ionized hypomagnesemia due to chelation of Mg with citrate. Similar to calcium, Mg may undergo saponification and be sequestered in necrotic fat during acute pancreatitis. Lactation may influence Mg balance because the Mg content of both canine and feline milk tends to be higher in the first few days of lactation. In addition, lactation’s influence on parathyroid hormone and circulating calcium concentrations most likely influences renal and intestinal handling of Mg.

Both increased renal excretion and gastrointestinal losses account for the major disturbances in circulating Mg concentrations. Various disorders such as acute or chronic diarrhea, malabsorptive syndromes (e.g., protein-losing enteropathy), short-bowel syndrome, or vomiting can lead to decreased intestinal absorption and excessive Mg loss from the body. Renal losses can occur with acquired intrinsic renal diseases (e.g., infections, nephrotoxins, ischemia) by causing renal Mg wasting through renal tubular dysfunction and decreased renal absorption. Renal Mg wasting may also result from a high tubular flow rate due to extracellular fluid volume expansion, diuretic therapy, or disease states such as feline hyperthyroidism. Diabetic ketoacidosis or posturethral obstructions result in profound diuresis and are commonly associated with hypomagnesemia.

Clinical Signs

The predominant clinical signs of hypomagnesemia result from abnormalities involving the cardiovascular, neuromuscular, and endocrine systems. Clinical signs depend on the degree and rate of decline, as well as on the temporal nature (acute versus chronic) of Mg deficiency.

The myocardial effects of Mg are linked to its role as a regulator of other ions, primarily calcium and K. For this reason, one of the most dramatic clinical signs associated with hypomagnesemia is cardiac arrhythmia such as atrial fibrillation, supraventricular tachycardia, and ventricular tachycardia or fibrillation. Prior to seeing overt arrhythmias, electrocardiographic (ECG) changes may occur, such as prolongation of the PR interval, widening of the QRS complex, depression of the ST segment, and peaking of the T wave.

Mg deficiency can result in various nonspecific neuromuscular signs caused by changes in the resting membrane potential, signal transduction, and smooth muscle tone. If present, concurrent hypocalcemia and hypokalemia may also contribute. Clinical manifestations of hypomagnesemia include skeletal muscle weakness or fasciculations, seizures, and ataxia. Esophageal or respiratory muscle weakness can manifest as dysphagia or dyspnea, respectively.

Metabolic complications of hypomagnesemia include concurrent hypokalemia, hyponatremia, hypocalcemia, and hypophosphatemia. Isolated Mg deficiency is uncommon. Mg’s role as a cofactor for sodium-potassium (Na/K) and calcium adenosine triphosphatase (ATPase) pumps likely plays a role in the development of concurrent electrolyte disturbances. Reduced Na/K-ATPase function in states of Mg deficiency leads to extracellular K loss. In addition, hypomagnesemia impairs the function of the Na/K-chloride cotransport system, decreasing K reentry into the cell. Overall, K accumulates extracellularly and is subsequently lost from the body due to ineffective renal K reabsorption. Urinary sodium loss generally occurs concurrently with K. The most likely origin of concurrent hypocalcemia is renal loss via reduced calcium ATPase pump function with decreased bone mobilization from impaired parathyroid function. Hypophosphatemia is thought to occur from increased renal phosphate loss. Concurrent hypokalemia or hypocalcemia that is refractory to aggressive potassium or calcium supplementation may be due to hypomagnesemia.

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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Approach to Hypomagnesemia and Hypokalemia
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