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Calcium, magnesium and phosphate
Over 99% of body calcium is in bone, of which about 1% is freely exchangeable with
extracellular fluid (ECF). Ionised calcium is crucial to many excitatory processes,
including nerve and neuromuscular conduction/contraction and coagulation. Normal
daily intake is of the order of 10–20mmol and normal total serum calcium is in the range
2.25–2.7mmol l−1. Intestinal calcium absorption is enhanced by 1,25-dihydroxy-vitamin
D3 (1,25(OH)2D3). Around 40% is bound to albumin and total serum calcium decreases
0.02mmol l−1 for each 1g l−1 decrease in albumin. Ionised calcium is the physiologically
important form and the normal level is 1.15mmol l−1.
Hypocalcaemia occurs when calcium is lost from the ECF (most commonly through renal
mechanisms) in greater quantities than can be replaced by bone or the intestine. Common
causes of hypocalcaemia are:
• Renal failure.
• Alkalosis (reduced ionised calcium).
• Citrate toxicity (massive transfusion).
As a result of reduced absorption of dietary divalent cations or poor dietary intake,
hypocalcaemia and hypomagnesaemia often coexist.
The symptoms of hypocalcaemia correlate with the magnitude and rapidity of the
decrease in serum calcium. The main features include neuromuscular irritability
evidenced by extremity and circumoral paraesthesiae, Chvostek and Trousseau signs,
muscle cramps, tetany, laryngospasm and seizures. A prolonged QT is seen on ECG and
may progress to VT/VF and hypotension.
Appropriate therapy depends on the severity of the hypocalcaemia and its cause. The
serum magnesium and phosphate should be checked and, if low, corrected. Chronic
asymptomatic mild hypocalcaemia can be treated with oral calcium supplements. If
metabolic acidosis accompanies hypocalcaemia, calcium must be corrected before the
acidosis is corrected. Calcium and hydrogen ions compete for protein-binding sites, so an
increase in pH will lead to a rapid decrease in ionised calcium. In the presence of acute
symptomatic hypocalcaemia, an intravenous bolus of calcium (100–200mg or 2.5–
5mmol) should be given over 5min. This can be followed by a maintenance infusion of
1–2mg kg−1 h−1. Calcium chloride 10% contains 27.2mg Ca ml−1 (0.68mmol ml−1) and
calcium gluconate 10% contains 9mg ml−1 (0.225mmol l−1). Calcium gluconate causes
less venous irritation than calcium chloride.
Calcium management following parathyroidectomy
In chronic renal failure the glomerular filtration rate (GFR) decreases and phosphate
(PO4) is not excreted. Phosphate levels in the blood rise and this decreases the level of the
active metabolite of 1,25(OH)2D3. As a result, patients have hypocalcaemia and defective
bone mineralisation. The low calcium stimulates the parathyroid gland to increase
production of parathyroid hormone, PTH (secondary hyperparathyroidism). If the
secondary hyperparathyroidism is prolonged, the secretion of PTH becomes
autonomous—tertiary hyperparathyroidism. This leads to high calcium levels. High
calcium and high PO4 levels cause precipitation of calcium in tissues and organs. After
total or partial parathyroidectomy the calcium level can fall rapidly, particularly in
patients who have evidence of ‘hungry bone syndrome’ (high alkaline phosphatase).
These patients may need large quantities of i.v. calcium replacement. Some patients have
hypercalcaemia with calcification of small and medium blood vessels, leading to skin
necrosis and ulcers particularly on their legs. This is called calciphylaxis and these
patients’ calcium levels should be kept at the lower limit of normal.
Calcium infusion after parathyroidectomy
Following parathyroid surgery, calcium infusions are best given through central
intusions, as peripheral i.v. may cause necrosis. Calcium levels should be checked 4-
hourly until stable, then 6-hourly. Check the patient’s alkaline phosphatase level
preoperatively: the higher the level, the more likely postoperative low serum calcium
levels and symptoms will occur. Prescribe oral calcium medications. If the corrected
calcium level is <2.4mmol l−1, commence a calcium infusion.
Dilute 20ml 10% calcium chloride in 100ml 0.9% sodium chloride (Table 2). Check
corrected calcium 4-hourly, and adjust rate (Table 3).
If the patient has tertiary hyperparathyroidism or calciphylaxis, choose the lower
infusion rate; if they have alkaline phosphatase >300units/l, choose the higher infusion
All patients require oral calcium, 1g, 8-hourly, and calcitriol, 0.5–1.0μg daily in two
divided doses, as soon as they are able to drink
Hypercalcaemia occurs generally when the influx of calcium from bone or the intestine
exceeds renal calcium excretory capacity. Common causes include:
• Hyperparathyroidism (accounts for >50% of cases).
• Neoplasms (primary with ectopic PTH secretion, secondary with bone metastases).
• Sarcoidosis (increased production of 1,25(OH)2D3 by granulomatous tissue).
• Drugs (thiazides and lithium).
• Immobilisation of any cause.
• Vitamin D intoxication.
The symptoms associated with hypercalcaemia depend on the rate of rise as well as the
absolute level of calcium. Mild hypercalcaemia is usually asymptomatic. Severe
hypercalcaemia causes neurological, gastrointestinal and renal symptoms. Neurological
features range from mild weakness, depression, psychosis and drowsiness but may
progress to coma. Gastrointestinal effects include nausea, vomiting, abdominal pain,
constipation, peptic ulceration and pancreatitis. Nephrogenic diabetes insipidus (DI),
renal stones, nephrocalcinosis and ectopic calcification may occur.
The underlying cause of hypercalcaemia must be treated. The measures taken will depend
on the calcium level. Most cases of mild hypercalcaemia are caused by primary
hyperparathyroidism and many will require parathyroidectomy. Patients with
symptomatic moderate (serum calcium >3.0mmol l−1) or severe (>3.4mmol l−1)
hypercalcaemia require intravenous saline to restore intravascular volume and enhance
renal calcium excretion. Thiazide diuretics should be avoided but furosemide (frusemide)
will enhance calcium excretion. Patients with severe hypercalcaemia associated with
raised PTH should be referred for urgent parathyroidectomy. Bisphosphonates (e.g.
etidronate, sodium pamidronate) have become the main therapy for the management of
hypercalcaemia due to enhanced osteoclastic bone reabsorption. Steroids are effective in
hypercalcaemia associated with haematological malignancies and in diseases related to
1,25(OH)2D3 excess (e.g. sarcoidosis and vitamin D toxicity).
Magnesium is essential for normal cellular and enzyme function. The total body
magnesium store is about 1000mmol, of which 50–60% is in bone. The normal plasma
range is 0.7–1.0mmol l−1 but because it is primarily an intracellular ion the plasma level
does not reflect total body stores. The normal daily intake is 10–20mmol, which is
balanced by urine and faecal losses. The kidney is the primary organ involved in
Hypomagnesaemia occurs in up to 65% of critically ill patients and is often associated
Usually follows loss of magnesium from the gastrointestinal tract or kidney.
• Gastrointestinal causes include prolonged nasogastric suction or vomiting, diarrhoea,
extensive bowel resection, severe malnutrition and acute pancreatitis.
• Renal losses occur with volume expanded states, hypercalcaemia, diuretic therapy,
alcohol, aminoglycosides and cisplatin exposure and the polyuric phase of acute
• Other causes include phosphate depletion, hyperparathyroidism and diabetes mellitus.
Most of the symptoms of hypomagnesaemia are rather non-specific. The accompanying
ion abnormalities such as hypocalcaemia, hypokalaemia and metabolic alkalosis account
for many of the clinical features. Neurological signs include confusion, weakness, ataxia,
tremors, carpopedal spasm and seizures. A wide QRS, long PR, inverted T, and U wave
may be seen on ECG. Arrhythmias may occur, including severe ventricular arrhythmias
(torsades de pointes), and there is increased potential for cardiac glycoside toxicity.
The underlying cause must be addressed. Symptomatic moderate-to-severe
hypomagesaemia will require parenteral therapy. In the event of an acute arrhythmia or
seizure, 8–10mmol of magnesium sulphate can be given over 5min followed by 25mmol
over 12h. The rate should be titrated against serum levels. Potassium should be replaced
at the same time. Oral magnesium sulphate is a laxative and may cause diarrhoea.
Hypermagnesaemia is usually iatrogenic (e.g. excess i.v. administration). High
magnesium levels antagonise the entry of calcium and prevent excitation.
These include hypotension, bradycardia, drowsiness and hyporeflexia (knee jerk is a
useful clinical test and is lost above 4mmol l−1). Levels >6mmol l−1 cause coma and
Administration of magnesium should be stopped. Calcium chloride will antagonise the
effect of magnesium. Diuretics increase renal loss. In severe cases dialysis may be
Total body phosphate in adults is about 700g: approximately 85% is in bone and 15% is
in extracellular fluid and soft tissue. Phosphate is found in adenosine triphosphate (ATP),
2,3-diphosphoglycerate (2,3-DPG) in red blood cells, phospholipids and phosphoproteins.
Phosphate is essential in many cellular functions and also acts as a buffer. The normal
serum level is 0.85–1.4mmol l−1.
Hypophosphataemia results from internal redistribution, increased urinary excretion and
decreased intestinal absorption.
• Internal redistribution of phosphate may result from respiratory alkalosis, refeeding
after malnutrition, recovery from diabetic ketoacidosis and the effects of hormones
and other agents (insulin, glucagon, adrenaline (epinephrine), cortisol, glucose).
• Increased urinary excretion of phosphate occurs in hyperparathyroidism, vitamin D
deficiency, malabsorption, volume expansion, renal tubular acidosis and alcoholism.
• Decreased intestinal absorption of phosphate occurs in antacid abuse, vitamin D
deficiency and chronic diarrhoea.
The clinical features are usually seen when the phosphate level has fallen below 0.3mmol
l−1. They are often non-specific but may include weakness (which may contribute to
respiratory failure and problems with weaning from mechanical ventilation), cardiac
dysfunction, paraesthesia, coma and seizures.
The underlying cause should be corrected. Oral phosphate can be given in doses of 2–3g
daily. When needed, 10mmol potassium phosphate can be given i.v. over 60min and
repeated depending on measured levels (a sodium phosphate preparation is also
available). There is a risk of hypocalcaemia associated with i.v. replacement and serum
calcium must be maintained.
Renal failure is the most common cause.
• Reduced renal excretion: renal failure, hypoparathyroidism, acromegaly,
bisphosphonate therapy and magnesium deficiency.
• Increased exogenous load: i.v. infusion, excess oral therapy, phosphate-containing
• Increased endogenous load: tumour lysis syndrome, rhabdomyolysis, bowel infarction,
malignant hyperthermia, haemolysis and acidosis.
• Pseudohyperphosphataemia: multiple myeloma.
Hypocalcaemia and tetany may occur with rapid rise in level. A large rise in
calcium×phosphate product causes ectopic calcification in tissues, nephrocalcinosis and
Aluminium hydroxide is used as a binding agent. Magnesium and calcium salts are also
effective and aluminium accumulation is a risk. Dialysis may be required.
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