The renal lesions of electrolyte imbalance. IV. The intranephronic calculosis of experimental magnesium depletion.

A dietary depletion of magnesium in rats leads to the production in the thin limb of Henle's loop of the nephrons of spherical microliths composed of a matrix of PAS-positive substances and calcium phosphate (3). These microliths grow by accretion to form intranephronic calculi. The classical pathological syndrome of clinical nephrolithiasis is thus reproduced within the nephron; to wit, the origin of the calculus at a certain level, local traumatic damage at the site of its origin, passage with the fluid flow down the urinary passages, lodgment of the calculus at some restricting point, obstruction of fluid flow and the usual consequent localized intrarenal "hydronephrotic" alterations of regressive atrophic cellular dysplasias within the nephron. To the classical description of the two forms of urinary lithiases occurring in the bladder and in the renal pelvis must therefore be added a third form, intranephronic calculosis. From the first origin of a microlith to its ultimate form as a calculus its organized structure is characterized by its matrix (PAS-positive materials) in which the periodic precipitation of crystalline mineral (Ca(++), PO(3) (---)) occurs in a pattern simulating Liesegang rings.

Efficacy of intravenous phosphorus therapy in the severely hypophosphatemic patient.

To evaluate the efficacy and safety of a simple approach to intravenous (IV) phosphorus therapy, ten adult patients with severe hypophosphatemia (less than or equal to 1 mg/dL) and normal renal function were studied prospectively. They were treated with a solution containing 9 mmole of phosphorus as monobasic potassium phosphate (KH2PO4), infused continuously every 12 hours. Serum phosphorus, potassium, and calcium levels and urinary excretion of phosphorus were measured every 12 hours. The serum phosphorus level was significantly improved at 12 hours, more than 1 mg/dL in all patients at 36 hours, and normal in six patients at 48 hours. The serum potassium level was never above normal, and serum calcium levels declined in only one patient. Administration of 9 mmole of phosphorus as KH2PO4 every 12 hours is both safe and efficacious IV therapy for severe hypophosphatemia in the adult patient with normal renal function and without hyperkalemia or hypercalcemia.

Hypermagnesemia as a cause of refractory hypotension, respiratory depression, and coma.

Hypermagnesemia developed in a patient as a result of excess antacid ingestion, bowel obstruction, and renal failure. Before the diagnosis was considered, refractory hypotension, respiratory depression, and coma developed, all of which were eventually reversed through the lowering of the serum magnesium concentration by hemodialysis.

Frequency of hypomagnesemia in hospitalized patients receiving digitalis.

We examined the frequency of hypokalemia and hypomagnesemia in patients receiving digitalis. Serum sodium, magnesium, and potassium levels were determined in 136 serum samples sent to the laboratory for digoxin assay. Hyponatremia (less than or equal to 130 mEq/L) occurred most frequently (21%), followed by hypomagnesemia (less than or equal to 1.25 mEq/L) in 19%, hypokalemia (less than or equal to 3.5 mEq/L) in 9%, and hypermagnesemia (greater than or equal to 2.25 mEq/L) in 7%. The twofold frequency of hypomagnesemia (19%) contrasted with hypokalemia (9%) indicates that clinicians are more attuned to avoiding hypokalemia than hypomagnesemia in patients receiving digitalis. Because hypokalemia and/or hypomagnesemia may contribute to the toxic effects of digitalis, our observation suggests that hypomagnesemia may be a more frequent contributor than hypokalemia to induction of toxic reactions to digitalis. Routine serum magnesium determination in patients receiving digitalis, who often are also receiving potent diuretics, may assist in identifying additional patients at risk for the toxic effects of digitalis.

Refractory potassium repletion. A consequence of magnesium deficiency.

Experimental and clinical observations support the view that uncorrected magnesium (Mg) deficiency impairs repletion of cellular potassium (K). This is consistent with the observed close association between K and Mg depletion. Concomitant Mg deficiency in K-depleted patients ranges from 38% to 42%. Refractory K repletion due to unrecognized concurrent Mg deficiency can be clinically perplexing. Refractory K repletion as a consequence of Mg deficiency may be operative in patients with congestive failure, digitalis toxicity, cisplatin therapy, and in patients receiving potent loop diuretics. Therefore, we recommend that: (1) serum Mg be routinely assessed in any patients in whom serum electrolytes are necessary for clinical management and (2) until serum Mg is routinely performed consideration should be given to treating hypokalemic patients with both Mg as well as K to avoid the problem of refractory K repletion due to coexisting Mg deficiency.

Refractory potassium repletion due to cisplatin-induced magnesium depletion.

Cisplatin is a common cause of hypomagnesemia and hypokalemia due to renal magnesium (Mg) and potassium (K) losses. Magnesium plays an important role in the maintenance of intracellular K. An unrecognized and untreated Mg depletion can lead to a refractory K repletion. We describe two patients with hypomagnesemia-associated refractory hypokalemia following cisplatin following cisplatin therapy. Potassium supplementation failed to replace the K deficit. Profound hypokalemia persisted until hypomagnesemia was recognized and corrected. In neither patient was the concurrent hypomagnesemia recognized until the 11th and 9th hospital days. These two cases demonstrated the association of a refractory K repletion and an Mg deficiency. Thus, both serum K ion and Mg levels should routinely be assessed in patients who require cisplatin therapy.

Predictors of clinical hypomagnesemia. Hypokalemia, hypophosphatemia, hyponatremia, and hypocalcemia.

Four studies were conducted, each determining the frequency of hypomagnesemia in patients already found to have one abnormal electrolyte determination. Hypomagnesemia occurred in 42% of patients with hypokalemia, 29% of patients with hypophosphatemia, 27% of patients with hyponatremia, and 22% of patients with hypocalcemia. These observations suggest that detection of either hypokalemia, hypophosphatemia, hyponatremia, or hypocalcemia, all of which are routinely available determinations, should alert the clinician to order serum magnesium determinations because of the frequent association of hypomagnesemia with these electrolyte perturbations. Optimally, levels of serum Mg should be determined on a routine basis because of the frequency of the occurrence of hypomagnesemia in hospitalized patients.

Magnesium deficiency: pathogenesis, prevalence, and clinical implications.

Hypomagnesemia is probably the most underdiagnosed electrolyte deficiency in current medical practice. Patients with cardiovascular disease who are at greatest risk for the development of magnesium deficiency are those treated with diuretics or digitalis. Both potassium and magnesium deficiencies are associated with increased ventricular ectopy and may increase the risk of sudden unexpected death. Refractory potassium repletion can be caused by concomitant magnesium depletion, and can be corrected with magnesium supplementation. Routine serum magnesium determination is recommended whenever the testing of electrolyte levels is required, especially in patients taking diuretic drugs or digitalis. Because hypomagnesemia is not necessarily present in a magnesium-deficient state, it is recommended that both potassium and magnesium be repleted in patients with hypokalemia. Potassium-/magnesium-sparing diuretics may be helpful in the prevention of these electrolyte deficiencies.

Magnesium deficiency. Causes and clinical implications.

The many causes of clinical magnesium deficiency can be placed into 2 categories: diminished intake of magnesium, and enhanced losses of magnesium, either through the gastrointestinal tract or through the kidneys. Examples of the first category include alcoholism, starvation, anorexia due to neoplastic disease and/or chemotherapy. Examples of the second category include severe diarrhoeal states, gastrointestinal fistulae, malabsorption, diuretic therapy and gentamicin therapy. Estimates of the prevalence of clinical hypomagnesaemia range from 6 to 11% in hospitalised patients. Serum predictors of associated clinical magnesium depletion include hypokalaemia (42%), hyponatraemia (23%), hypophosphataemia (22%) and hypocalcaemia (20%). Experimental and clinical observations strongly support the view that magnesium and potassium are closely linked at the cellular level. Magnesium has been demonstrated to be important in cell energetics (Mg++-activated ATPase), in maintenance of the integrity of cell membranes, retardation of cell loss of potassium, as well as enhancing repletion of cell potassium. While translation of these experimental observations into clinical terms encompasses a wide spectrum of illnesses, there is special relevance in considering the role of magnesium in repletion and maintenance of cell potassium in 2 clinical instances: (a) patients treated with digitalis and diuretics; and (b) hypertensive patients. In these types of patients not only potassium but also magnesium should be administered together to avoid the problem of cell potassium depletion and refractory potassium repletion associated with coexisting and uncorrected magnesium depletion.

Preoperative administration of fluids.

A study by questionnaire was sent to 134 Surgical Services at Veterans Administration Hospitals to ascertain the prevalence of the practice of preoperative hydration during the period of hydropenia preceding surgery. A 92.5 per cent response was noted and the following conclusions are drawn: (1) The majority of Veterans Administration Surgical Services do not routinely provide intravenous fluids during the immediate preoperative period. (2) Affiliation with a medical school-based postgraduate training program does not alter significantly the proportion of Surgical Services providing preoperative intravenous therapy on a routine basis. (3) These observations suggest a need for Surgical Services to assess the desirability and indications of preoperative hydration. (4) However, in the case of chronic renal failure patients there is little question of the necessity for careful preoperative, intraoperative, and postoperative hydration.

Hyperkalemia: diagnosis and treatment.

We have considered a differential diagnosis of clinical hyperkalemia. The clinical signs and symptoms of patients with hyperkalemia are manifold and can involve many organ systems. The nonoliguric chronic renal failure patient with hyporeninemia and hypoaldosteronemia may have as one of his principal problems recurrent hyperkalemia. Treatment of this condition includes well-known modalities such as administration of calcium salts, NaHCO3, removal of potassium with resin or dialysis as well as placement of a transvenous pacemaker in anticipation of bradyarrhythmias or asystole.

Magnesium and potassium supplementation in the prevention of diabetic vascular disease.

Vascular disease underlies many of the complications of diabetes and includes coronary, cerebral, renal, peripheral and retinal vascular abnormalities. Magnesium (Mg) and potassium (K) deficiencies occur frequently in diabetic patients. Because of the vasoconstrictive effects of hypomagnesemia and hypokalemia and the adverse effects of Mg and K deficiency on carbohydrate metabolism we hypothesize that routine Mg and K supplementation of all hypomagnesemic diabetics will ameliorate or prevent the ravages of diabetic vascular disease.

Carbohydrate-electrolyte solutions during field training: an overview.

The rationale and methods of evaluating two carbohydrate-electrolyte solutions at a field training exercise in hot weather are presented in this overview. The carbohydrate-electrolyte solutions were formulated to produce a multipurpose replacement beverage which could satisfy diverse requirements of troops working in hot climates. Several uses of these beverages include replacement of electrolytes and fluid while in Mission Oriented Protective Posture IV, fluid replacement for mild heat casualties, and oral rehydration therapy for treatment of diarrheal losses.

Acceptability and effect of carbohydrate-electrolyte solutions on electrolyte homeostasis during field training.

Two lemon-lime flavored 2.5% carbohydrate-electrolyte solutions (CE1 supplemented with Na+, K+, and Mg+; and CE2 supplemented with NA+) were compared to plain water (water) and lemon-lime flavored water placebo (placebo) to evaluate their acceptability and consumption during 8 days of field training in hot weather. Acceptability ratings and consumption of CE2 and the flavored water placebo were similar and greater, respectively, than those for CE1. Average Na+ and K+ intakes, and serum electrolytes levels, were not affected during the 8-day trial. If food intake is adequate, consumption of carbohydrate-electrolyte solutions is apparently unnecessary to maintain electrolyte homeostasis.

Incidence of hypohydration when consuming carbohydrate-electrolyte solutions during field training.

Carbohydrate-electrolyte solutions (CE1, CE2) were evaluated for their ability to reduce the incidence of hypohydration during field training in hot weather (max Tamb = 88 degrees-100 degrees F). Hydration status was monitored twice daily in Army reservists who consumed ad libitum CE1, or CE2, or water, or a flavored water placebo. The water group had the highest percentage incidence of urine specific gravity greater than or equal to 1.030 (22%), whereas CE2 and flavored water placebo groups had the lowest (6% and 8%, respectively). Average total fluid intake was greatest in CE2 and lowest in CE1. CE2 and flavored water placebo were more effective than CE1 and water in reducing the overall incidence of hypohydration during this field exercise.

Routine serum magnesium determination: a contemporary clinical imperative.

Identification of hypomagnesaemia or hypermagnesaemia is presently the most expeditious method of clinically identifying perturbations in Mg metabolism. Clinicians may overlook as much as 90% of clinical hypomagnesaemia and hypermagnesaemia when serum Mg is determined on order versus on a routine basis. Routine serum Mg determination will facilitate management of digitalis toxicity in patients who are not currently identified as being hypomagnesaemic as well as preventing the occurrence of refractory K repletion. In our opinion routine serum Mg determination represents a clinical need which has not been addressed to date.

Clinical disorders of magnesium metabolism.

Normal Mg metabolism has been reviewed. The most expeditious method of identifying disorders of Mg deficiency or excess is to order a serum Mg determination. In our opinion, routine serum Mg would significantly enhance the clinician's ability to identify disorders of Mg metabolism. Refractory K repletion can be avoided by identifying co-existing hypomagnesemia in hypokalemic patients; as a result, prompting the clinician to institute simultaneous repletion of Mg as well as K. While oral Mg is the preferred route of repletion in critically ill patients, intravenous administration of Mg is recommended. Refractory hypotension, mental obtundation, and respiratory arrest occur with significant hypermagnesemia. Hemodialysis is recommended for treatment of symptomatic hypermagnesemia.

Electrolyte & water metabolism in sports activities.

Few studies in water and electrolyte metabolism during sports activities have directed attention to magnesium. Addition of magnesium to sports beverages in appropriate concentrations appears to be safe. This article considers the potential role and availability of magnesium in fluid repletion during sports activities.

Health screening in elderly Oklahomans.

A total of 550 males and 457 females in their 60s and 70s were screened for height and weight, blood pressure, glucose, cholesterol, and hemoglobin. Statistical analysis was performed using SAS software. Male values were abnormal for all screening parameters except for cholesterol. Statistically significant lower hemoglobin in males suggests that blood loss may be a problem, and in males increases in body weight and glucose may herald a higher frequency of cardiovascular disease. Control of blood pressure, weight reduction, decreased consumption of fat and salt, and regular exercise may be the health imperatives in this group of elderly Oklahomans.