Hypocalcaemia



This is a low plasma calcium i.e. less than 2.3 mmol per l.
It is far less common than hypercalcaemia
because the skeleton is a readily mobilisable calcium reserve.

Note that reference ranges may vary between different laboratories.

Acute hypocalcaemia



Commonly:

Hyperventilation inducing a transient hypocalcaemia;
serum total calcium levels normal

Less commonly:

- Alkalosis due to alkali infusion to treat acidosis / Salicylate poisoning
- High phosphate:
   - rapid tumour lysis - e.g. cytotoxic treatment of leukaemia
   - Excessive phosphate intake -
   e.g.
   - phosphate containing enemas,
   - excessive oral phosphate (infant milk feeds),
   - parenteral phosphorous
- High citrate from massive blood transfusion if liver cannot metabolise adequately
- Acute pancreatitis

Chronic hypocalcaemia



Commonly:

- Vitamin D deficiency - dietary lack, malabsorption, lack of sunlight
- Chronic renal disease - due to failure of renal conversion of 25 HCC to 1,25 DHCC


Less commonly:

- hypoparathyroidism - including hypomagnesaemia
- pseudohypoparathyroidism
- low plasma albumin - malnutrition, liver disease


Rarely:
- dietary lack:
- low intake
- binding of calcium by organic phosphates
- for example, presence of phytate in chapati flour may be important in Asian people

Clinical features of hypocalcaemia



1. The predominant effects of hypocalcaemia are on the nerves and muscles.
Typical features include:

- Tetany, painful cramps, and tingling in the extremities
- latent tetany may be demonstrated by Trousseau's and Chvostek's signs
- severe tetany may result in spontaneous spasm of the hand - main d'accoucheur - largely precipitated by exercise
- laryngeal spasm may cause stridor, obstructed respiration
- convulsions may occur as hypocalcaemia lowers the seizure threshold

2. Chronic hypocalcaemia may cause psychiatric effects
- from general malaise to overt psychosis

3. Other features depend on the underlying cause.

They are more features of chronic disease and may include:
Candidosis,
Dystrophic nails,
Alopecia,
Intracranial calcification especially of basal ganglia,
Cataracts,
Addison's disease,
Mental deficiency,
Papilloedema,
Prolonged QT on ECG - from hypoparathyroidism
Rickets / osteomalacia - from vitamin D deficiency

Trousseau's sign of latent tetany



This is a sign of latent tetany.
Compression of the forearm in subjects having undue neuromuscular excitability due to hypocalcaemia
produces spasm in the hand and wrist. The thumb is adducted, the fingers bunched and the wrist flexed.

Chvostek's sign



Chvostek's sign is contraction of the muscles of the eye, nose or mouth,
elicited by tapping along the course of the facial nerve.
The examiner taps gently over the facial nerve in front of the ear.

This is a sign of a latent tetany.

Diagnosis



Uraemia and an elevated serum creatinine indicate chronic renal failure

Elevated serum phosphate and normal renal function indicate hypoparathyroidism
- skeletal abnormalities will indicate pseudohypoparathyroidism

Hypoparathyroidism due to hypomagnesaemia
produces a hypocalcaemia uncorrected by calcium

Treatment of hypocalcaemia



Treatment depends on the primary disease and severity of symptoms:

treatment usually commences with administration of calcium
form of calcium and the need for additional agents such as vitamin D
depends on the acuity and severity of the hypocalcaemia
as well as the underlying cause

Patients with symptomatic hypocalcaemia
or those with corrected serum levels of 1·875 mmol/L (7·5 mg/dL) or less
treated with parenteral calcium until the symptoms cease or the calcium concentration rises above this point

In acute symptomatic hypocalcaemia there is a rapid decrease in serum calcium
associated with signs and symptoms of hypocalcaemia
generally occurs at concentrations of 1·875 mmol/L (7·5 mg/dL) or less

Infusion of 15 mg/kg (3·75 mmol/kg) of elemental calcium over 4-6 h
will increase the total serum calcium by 0·5-0·75 mmol/L (2-3 mg/dL)

Chronic, asymptomatic mild hypocalcaemia


is usually treated with oral calcium supplements

note that calcium binds with dietary phosphate and oxalate to form insoluble and unabsorbable salts
- therefore calcium is better absorbed when taken between meals

patients with little or no PTH are usually treated with calcium and vitamin D
treatment of chronic hypocalcaemia requires oral calcium to increase availability for intestinal absorption
and, often, vitamin D to enhance absorption
teatment usually begins at a daily dose of 1000-2600 mg (250-650 mmol)
divided into two, three, or four doses
and taken between meals,
the dose of oral calcium is adjusted according to follow-up calcium levels

calcium carbonate is widely available in tablets containing 500-750 mg calcium

calcium citrate is well absorbed
- however it enhances aluminium absorption
and may predispose to aluminium toxicity in patients with renal insufficiency

calcium phosphate should be avoided because it may exacerbate hyperphosphataemia
and metastatic calcification


when the hypocalcaemia is associated with insufficient vitamin D,
replacement of the vitamin D is usually required

oral 1,25(OH)2D3

acts rapidly since it requires no further metabolism to function
0·5-1·0 µg daily is generally sufficient
- however in extreme cases (e.g. immediately post-parathyroidectomy) larger doses may be required

vitamins D2 or D3

are adequate to avoid nutritional deficiency at doses of 400 units a day
or for malabsorption at higher doses (50 000-100 000 units)

vitamins D2 and D3 require conversion to 1,25(OH)2D3 for maximal biological action
therefore they are not suitable if the 25- or 1a-hydroxylation are impaired

causes of impairement of 25- or 1a-hydroxylation include
liver and renal failure,
hypoparathyroidism,
and vitamin-D-dependent rickets type 1
in contrast to the rapid elimination of 1,25(OH)2D3,
vitamins D2 and D3 may continue to function for several weeks,
potentially resulting in hypervitaminosis D

Notes:

General principles apply to the management of a hypocalcaemic patient
Magnesium level should be checked and, if low, corrected

In a setting of sepsis or renal failure,
metabolic acidosis may accompany hypocalcaemia
and calcium must be replaced before the acidosis is corrected

Calcium and Hydrogen ions compete for protein-binding sites
therefore an increase in pH with alkali therapy
will increase the binding sites for calcium
leads to a rapid fall in ionised calcium,
potentially resulting in cardiac arrest
- therefore calcium levels should be corrected first

Sodium bicarbonate and calcium salts must be infused in separate lines
to avoid precipitation of calcium carbonate

Patients on digoxin should be monitored carefully
because administration of calcium
may potentiate digitalis toxicity and cause death

Patients with hypoparathyroidism
have decreased renal calcium reabsorption

Oral calcium supplementation, especially with concomitant vitamin D administration,
increases the filtered load of calcium and results in hypercalciuria
with possible nephrocalcinosis or nephrolithiasis
in this situation serum calcium levels should be maintained at the lower limit of normal
with 24 h urinary calcium excretion kept below 1 mmol/kg (4 mg/kg)

thiazide diuretics

increase renal calcium reabsorption
and may be useful in patients with hypoparathyroidism

hyperphosphataemia

may accompany hypocalcaemia in patients with
hypoparathyroidism, renal disease, rhabdomyolysis, and tumour lysis
in this situationm, to avoid soft-tissue calcium phosphate precipitation,
calcium supplementation should be accompanied by oral phosphorus binders
also, if possible, calcium supplementation should be delayed
until the serum phosphate has fallen below 1·5 mmol/L (6 mg/dL)
Reference:

(1) Bushinksy DA, Monk RD. Calcium. Lancet 1998; 352 (9124): 306-311.