SeriesMagnesium and phosphorus
Section snippets
Magnesium homoeostasis
While the distribution of magnesium may flow between stores in bone or muscle and the extracellular fluid (ECF). TBMg depends mainly on gastrointestinal absorption and renal excretion.
The average daily dietary intake fluctuates between 300 and 350 Mg, and intestinal absorption is inversely proportional to the amount ingested. Mg2+ absorption occurs by a saturable transport system and passive diffusion.
The kidney is the principal organ involved in magnesium regulation. About 100 mg is excreted
Causes of magnesium deficiency
Hypomagnesaemia (figure 1) is often found in inpatients (eg, 65% of those intensive care and up to 12% of these on general wards).3 The usual reason is loss of magnesium from the gastrointestinal tract or the kidney (panel 1).
Depletion by gastrointestinal causes occurs during acute or chronic diarrhoea, in the presence of malabsorption steatorrhoea, and after extensive bowel resection. There is also a rare inborn error of metabolism (primary intestinal hypomagnesaemia) characterised by a
Clinical manifestations
Most of the symptoms of moderate to severe hypomagnesaemia (panel 2) are non-specific and symptomatic magnesium depletion is usually associated with additional ion abnormalities such as hypocalcaemia, hypokalaemia, and metabolic alkalosis.5
Hypocalcaemia is typical in severe hypomagnesaemia, and its degree seems to be related to the severity of the magnesium depletion, usually appearing at a serum [Mg2+] below 0·49 mmol/L. Patients may present evidence of neuromuscular hyperexcitability, with
Diagnosis
There is no consensus on what is an abnormally low plasma [Mg2+]. However, a concentration below 0·75 mmol/L usually indicates some degree of magnesium depletion. If gastrointestinal or renal losses cannot be distinguished, measurement of 24 h Mg2+ excretion or the fractional excretion should help. In some patients a magnesium-tolerance test (measuring urinary Mg2+ excretion over 24 h after an intravenous magnesium load9, 10) can be useful.
Treatment
The choice of route of magnesium repletion varies with the severity of the clinical findings. An acute infusion of magnesium could decreased magnesium reabsorption in the loop of Henle, most of the infused magnesium ending up in the urine. For this reason, oral replacement is preferred, especially in the symptom-free patients. Commercial preparations, contain magnesium chloride or lactate and provide 2·5–3·5 mmol per tablet. In severe hypomagnesaemia 15–20 mmol in divided doses could be
Hypermagnesaemia
Hypermagnesaemia (a plasma [Mg2+] above 0·95 mmol/L would be considered abnormal) is rare and usually iatrogenic—eg, after intravenous magnesium or when magnesium-containing cathartics or antacids have been given. Those most at risk are the elderly and patients with bowel disorders or renal insufficiency.13 A new syndrome of hypokalaemic metabolic alkalosis with hypomagnesuric hypermagnesaemia and severe hypocalciuria has been recently described.14
Clinical manifestations of hypermagnesaemia
Phosphorus homoeostasis
The average diet provides 800–1400 mg phosphorus daily. 60–80% will be absorbed in the gut, mainly by passive transport but there is also active transport stimulated by 1,25-dihydroxyvitamin D3 (1,25[OH]2 D3).
Normal plasma phosphorus, usually expressed as phosphate-ranges between 0·89 and 1·44 mmol/L (2·8–4·5 mg/dL). Concentrations are higher in children, decreasing to adult values in late adolescence.15, 16
Phosphorus is freely filtered in the glomerulus. More than 80% of the filtered load is
Hypophosphataemia
Hypophosphataemia (figure 2), defined as a plasma phosphate below 0·97 mmol/L is observed in 0·25–2·15% of general admissions to hospitals,22, 23 but the frequency has been as high as 25% in selected series.24
Causes
Pathophysiological and mechanisms include internal redistribution, increased urinary excretion, and decreased intestinal absorption (panel 3). Combinations of these abnormalities are also common.
Internal redistribution is the most frequent cause of hypophosphataemia.16 The associated clinical conditions are acute respiratory alkalosis, increased insulin during glucose administration, recovery from diabetic ketoacidosis, and refeeding of malnourished patients. These conditions stimulate
Clinical manifestations
Symptomatic hypophosphataemia is usually observed when plasma phosphorus falls below 0·32 mmol/L, particularly with concurrent phosphate depletion. The most frequent risk factors or causes are alcoholism and alcohol withdrawal, recovery from diabetic ketoacidosis, total parenteral nutrition without phosphate supplementation, and chronic ingestion of phosphate-binding antacids. Hyperventilation is frequently a precipitating factor. The clinical manifestations of hypophosphataemia are diverse and
Treatment
When serum [P] is between 0·48 and 0·72 mmol/L with no clinical evidence of phosphate deficit there is no need for phosphorus administration. However, if risk factors for phosphate depletion are present, or if serum phosphorus falls below 0·32 mmol/L, replacement is advised.
The safest mode of therapy is oral. 1000 mg phosphorus per day will usually correct phosphate depletion. Cow's milk contains about 1 mg of phosphorus per mL. Oral phosphate can also be administered in tablets of sodium or
Causes
Hyperphosphataemia (figure 2) can occur as a consequence of increased exogenous phosphorus load or absorption in the gastrointestinal tract, increased endogenous load, decreased urinary excretion and pseudohyperphosphataemia (panel 4).
An increased exogenous phosphorus load means that the amount of phosphorus that enters the intravascular compartment overwhelms renal excretory capacity. This can happen with administration of high quantities of phosphate or by vitamin D overdose. Premature babies
Clinical manifestations
Hypocalcaemia and tetany may occur with rapid increases in plasma phosphate. A rise in the serum calcium X phosphorus product above 70 results in deposition of calcium in soft tissues, decreasing circulating calcium levels. Serum calcium also falls because phosphate inhibits renal lα-hydroxylase so that less 1,25(OH)2 D3 is produced. Ectopic calcification is a frequent complication in patients with chronic renal failure receiving supplements of vitamin D when correction of hyperphosphataemia is
Treatment
The most effective measure to correct hyperphosphataemia is reduction of intestinal absorption by a moderate decrease in protein intake and the ingestion of phosphate-binding salts of aluminium, magnesium, or calcium. In patients with renal failure, calcium salts are preferred bcause aluminium accumulation can have dangerous consequences.
Our work has been supported in part by grants Sl-1223, RP-IV-C139, and G-97000808 of the Consejo Nacional de Investigaciones Cientificas y Technologicas de
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