HYPOCALCEMIA

Definition
• Ionized calcium < 4.5 mg/dL;
total calcium < 8.5 mg/dL
if serum protein is normal
 Clinical manifestations
• The clinical manifestations of hypocalcemia
result from increased neuromuscular
irritability and include
muscle cramps,
carpopedal spasm (tetany),
weakness,
paresthesia,
laryngospasm,
and seizure-like activity
• Tetany can be detected by the Chvostek sign
(facial spasms produced by lightly tapping
over the facial nerve just in front of the ear) or
by the Trousseau sign (carpal spasms
exhibited when arterial blood flow to the
hand is occluded for 3 to 5 minutes with a
blood pressure cuff inflated to 15 mm Hg
above systolic blood pressure).
• Hypoproteinemia may lead to a false
suggestion of hypocalcemia because the
serum total calcium level is low even though
the ionized Ca2+ remains normal.
• It is best to measure serum ionized calcium if
hypocalcemia or hypercalcemia is suspected.
 ETIOLOGIC CLASSIFICATION OF
HYPOCALCEMIA
• PARATHYROID HORMONE DEFICIENCY
• PARATHYROID HORMONE RECEPTOR DEFECTS
(PSEUDOHYPOPARATHYROIDISM)
• MITOCHONDRIAL DNA MUTATIONS
• MAGNESIUM DEFICIENCY
• EXOGENOUS INORGANIC PHOSPHATE EXCESS
• VITAMIN D DEFICIENCY
 PARATHYROID HORMONE
DEFICIENCY
• Aplasia or hypoplasia of parathyroids
• Suppression of neonatal PTH secretion due to
maternal hyperparathyroidism
• Preproparathyroid hormone gene mutation
• Ca2+-sensing receptor activating mutation
• Autoimmune parathyroiditis
• Infiltrative lesions
• Primary hypoparathyroidism causes
hypocalcemia, but does not cause rickets.
 Etiology of primary
hypoparathyroidism
• Congenital malformation (e.g., DiGeorge syndrome
or other complex syndromes) resulting from
developmental abnormalities of the third and fourth
branchial arches
• Surgical procedures, such as thyroidectomy or
parathyroidectomy, in which parathyroid tissue is
removed either deliberately or as a complication of
surgery for another goal
• Autoimmunity (autoimmune polyglandular syndrome
type 1), which may destroy the parathyroid gland
 Pseudohypoparathyroidism
• Pseudohypoparathyroidism may occur in one
of four forms, all with hypocalcemia and
hyperphosphatemia.
• Neonatal tetany is most often noted in
premature or asphyxiated infants and infants
of diabetic mothers.
• Excessive phosphate retention, as occurs in
renal failure, also produces hypocalcemia.
• If the PTH concentration is not elevated
appropriately relevant to low serum calcium,
hypoparathyroidism (transient, primary, or
caused by hypomagnesemia) is present.
 Treatment
• Treatment of severe tetany or seizures
resulting from hypocalcemia consists of
intravenous calcium gluconate (1-2 mL/kg of a
10% solution) given slowly over 10 minutes,
while cardiac status is monitored by
electrocardiogram (ECG) for bradycardia,
which can be fatal.
• Long-term treatment of hypoparathyroidism
involves administering vitamin D, preferably as
1,25-dihydroxyvitamin D, and calcium.
• Therapy is adjusted to keep the serum calcium
in the lower half of the normal range to avoid
episodes of hypercalcemia that might produce
nephrocalcinosis and to avoid pancreatitis.
 Important Physiologic Changes in
Bone and Mineral Diseases
• Condition Calcium Phosphate Parathyroid Hormone 25(OH)D
Primary hypoparathyroidism ↓ ↑ ↓ Nl
Pseudohypoparathyroidism ↓ ↑ ↑ Nl
Vitamin D deficiency Nl(↓) ↓ ↑ ↓
Familial hypophosphatemic rickets Nl ↓ Nl (sl↑) Nl
Hyperparathyroidism ↑ ↓ ↑ Nl
Immobilization ↑ ↑ ↓ Nl
 RICKETS
• Rickets is defined as decreased or defective
bone mineralization in growing children;
osteomalacia is the same condition in adults.
• The proportion of osteoid (the organic portion
of bone) is excessive.
• As a result, the bone becomes soft and the
metaphyses of the long bones widen.
• In nutritional vitamin D deficiency, calcium is
not absorbed adequately from the intestine.
• Poor vitamin D intake (food fads or poor
maternal diet affecting breast milk vitamin D)
or avoidance of sunlight in infants exclusively
breastfed may contribute to the development
of rickets.
• Defects in vitamin D metabolism by the kidney
(renal failure, autosomal recessive deficiency
of 1α-hydroxylation, vitamin D-dependent
rickets) or liver (defect in 25-hydroxylation)
also can cause rickets.
• Rickets usually is treated with 1,25-
hydroxyvitamin D and supplemental calcium.
• In hypophosphatemic rickets, phosphate
supplementation (not calcium) must
accompany vitamin D therapy, which is given
to suppress secondary hyperparathyroidism.