Hypocalcemia

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Overview

Hypocalcemia is the presence of low serum calcium levels in the blood, usually taken as less than 3.5 mmol/L or 8.8 mg/dl or an ionized calcium level of less than 1.1 mmol/L (4.5 mg/dL). It is a type of electrolyte disturbance. In the blood, about half of all calcium is bound to proteins such as serum albumin, but it is the unbound, or ionized, calcium that the body regulates. If a person has abnormal levels of blood proteins then the plasma calcium may be inaccurate. The ionized calcium level is considered more clinically accurate in this case.

Calcium is the most abundant mineral in the body. 99% of the body's calcium is stored in bone. Calcium is found in plasma and is either protein-bound or ionized and readily available.

Alkalosis

As blood plasma hydrogen ion concentration decreases, caused by respiratory or metabolic alkalosis, freely ionized calcium concentration decreases. This freely ionized calcium is the biologically active component of blood calcium. Since a portion of both hydrogen ions and calcium are bound to serum albumin, when blood becomes alkalotic, bound hydrogen ions dissociate from albumin, freeing up the albumin to bind with more calcium and thereby decreasing the freely ionized portion of total serum calcium. For every 0.1 increase in pH, ionized calcium decreases by about 0.05 mmol/l.

This hypocalcemia related to alkalosis is partially responsible for the cerebral vasoconstriction that causes the lightheadedness, fainting, and parasthesia often seen with hyperventilation.

Differential Diagnosis Based Upon Pathophysiology

• Eating disorders
• Magnesium over supplementation
• Prolonged use of medications/laxatives containing magnesium
• Absent parathyroid hormone (PTH)
  • Hereditary hypoparathyroidism
  • Acquired hypoparathyroidism
  • Hypomagnesemia
  • Following parathyroidectomy, "Hungry Bone Syndrome"
  • Following thyroidectomy, the parathyroid glands are located very close to the thyroid and are easily injured or even accidentally removed during thyroidectomy
• Ineffective PTH
  • Chronic renal failure
  • Absent active vitamin D
    • Decreased dietary intake
    • Decreased sun exposure
    • Defective Vitamin D metabolism
      • Anticonvulsant therapy
      • Vitamin-D dependent rickets, type I
  • Ineffective active vitamin D
    • Intestinal malabsorption
    • Vitamin-D dependent rickets, type II
  • Pseudohypoparathyroidism
• Deficient PTH
  • Severe acute hyperphosphatemia
    • Tumor lysis syndrome
    • Acute renal failure
    • Rhabdomyolysis (initial stage)
  • Osteitis fibrosa following parathyroidectomy
• Exposure to hydrofluoric acid
• As a complication of pancreatitis
• As a result of hyperventilation.
• Chelation Therapy

Complete Differential Diagnosis of Hypocalcemia

In alphabetical order.

• Acute pancreatitis
• Adrenocortical hyperplasia
• Alcohol abuse
• Alkalosis
• Anticonvulsants
• Breast cancer
• Bronchial cancer
• Burns
• Chronic Renal Failure
• Cirrhosis
• Decreased ultraviolet/sun (vitamin D deficiency)
• DiGeorge's Syndrome
• Diuretic therapy
• Drugs
• Enemas, laxatives
• Enhanced bone formation
• Excessive secretion of calcitonin
• Familial hypocalcemia
• Hyperphosphatemia
• Hypoalbuminemia (pseudohypocalcemia)
• Hypomagnesiumia
• Hypoparathyroidism
• Hypoproteinemia
• Increased diuresis with physiologic saline solution
• Intravenous phosphate administration
• Kidney diseases with reduced formation of activated vitamin D
• Magnesium depletion
• Malabsorption
• Maldigestion
• Medullary carcinoma of the thyroid
• Neonatal tetany
• Nephrotic Syndrome
• Osteoblastic metastases
• Osteoporosis
• Polyglandular autoimmune syndrome
• Postoperative
• Pseudohypoparathyroidism
• Renal Failure
• Rhabdomyolysis
• Rickets
• Sepsis
• Septic shock
• Short Bowel Syndrome
• Steroid therapy
• Thyroid cancer
• Transfusion of citrated blood
• Tumor Lysis Syndrome
• Vitamin D deficiency

Diagnosis

History and Symptoms

• Fatigue
• Weakness
• Muscle cramping and spasm
• Nausea and vomiting
• Abdominal pain
• Depression
• Irritability
• Delirium
• Psychosis
• Seizures (with severe hypocalcemia)
• Perioral tingling and parasthesia, 'pins and needles' sensation over the extremities of hands and feet. This is the earliest symptom of hypocalcemia.

Signs

• Tetany, carpopedal spasm are seen.
• Latent tetany
  • Trousseau sign of latent tetany (eliciting carpal spasm by inflating the blood pressure cuff and maintaining the cuff pressure above systolic)
  • Chvostek's sign (tapping of the inferior portion of the zygoma will produce facial spasms)
• Tendon reflexes are hyperactive
• Life threatening complications
  • Laryngospasm
  • Cardiac arrhythmias

Clinical Features Associated with Hypocalcemia

• Abdominal pain
• Alopecia
• Anxiety
• Atopic eczema
• Biliary colic
• Brittle nails
• Bronchial spasm
• Calcification of cerebral cortex or cerebellum
• Cardiomyopathy
• Choreoathetosis
• Chvostek's sign
• Coarse hair
• Confusion
• Congestive heart failure
• Delayed tooth eruption
• Disorientation
• Dry skin
• Dysphagia
• Dyspnea
• Dystonic spasms
• Enamel hypoplasia
• Exfoliative dermatitis
• Extrapyramidal signs due to calcification of basal ganglia
• Fatigue
• Impaired intellectual ability
• Impetigo herpetiformis
• Increased dental caries
• Increased intracranial pressure
• Irritability
• Laryngeal spasm
• Muscle cramps
• Nonspecific EEG changes
• Papilledema
• Paresthesia
• Parkinsonism
• Personality disturbances
• Polymyositis
• Prolonged QT interval in EKG
• Psoriasis
• Psychoneurosis
• Psychosis
• Seizures (focal, petit mal, grand mal)
• Shortened premolar roots
• Subcapsular cataracts
• Tetany
• Thickened lamina dura
• Trousseau's sign
• Wheezing

Laboratory Findings

Suggested initial laboratory studies include the following:

• Serum calcium
• Ionized calcium
• Complete blood count
• Blood urea nitrogen (BUN)/creatinine
• Magnesium
• Albumin
• Phosphorus
• Amylase/lipase

Additional laboratory studies to be obtained as part of a more complete evaluation include the following:

• Vitamin D levels
• Parathyroid hormone

Electrocardiographic Findings

1. Prolongation of the QTc interval is the major EKG finding
2. There is a lengthening of the interval between the end of the QRS and the beginning of the T wave (i.e. ST-segment lengthening).

EKG examples

Prolonged QTc interval due to hypocalcemia

Management

• Two ampoules of intravenous calcium gluconate 10% is given slowly in a period of 10 minutes, or if the hypocalcemia is severe, calcium chloride is given instead.
• Maintenance doses of both calcium and vitamin-D (often as 1,25-(OH)₂-D₃, i.e. calcitriol)) are often necessary to prevent further decline.

See also

• Calcium metabolism
• Hypercalcaemia
• Calcium deficiency (plant disorder)
• Hypomagnesemia with secondary hypocalcemia

External links

• Cleveland Clinic
• Endotext
• EKG abnormalities associated with hypocalcemia
• Seizures due to hypocalcaemia worsened by shifting towards alkalosis by bicarbonate therapy
• Electrolytes

Acknowledgements

The content on this page was first contributed by: C. Michael Gibson, M.S., M.D.

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