Results from five mechanisms: decreased serum binding proteins, increased serum phosphate with increase in calcium-phosphate solubility product, increased in renal calcium excretion, decreased intestinal calcium absorption or loss of calcium to the skeleton.

Leads to reduction in the potential difference across cell membranes.

Ionized calcium is the necessary plasma fraction for normal physiologic processes, as it facilitates nerve conduction, muscle contraction, and muscle relaxation.

Calcium is necessary for bone mineralization.

Calcium is an important cofactor for hormonal secretion in endocrine organs, and at the cellular level is an important regulator of ion transport and membrane integrity.

Calcium turnover is estimated to be 10-20 mEq/day.

Approximately 500 mg of calcium is removed from the bones daily and needs to replaced by an equal amount.

The amount of calcium absorbed by the intestines is matched by urinary calcium excretion.

Ionized calcium levels remain stable because of control maintained by parathyroid hormone (PTH), vitamin D, and calcitonin through complex feedback loops, acting at bone, renal, and GI sites.

Calcium levels are also affected by magnesium and phosphorus levels.

Associated with heart failure, prolonged QT interval, and life-threatening cardiac arrhythmias and sudden death.

Almost 1/3 of all heart failure patients suffer from hypocalcemia and an associated poor prognosis.

PTH stimulates osteoclastic bone reabsorption and distal tubular calcium reabsorption.

PTH mediates 1,25-dihydroxyvitamin D (1,25[OH]2 D) intestinal calcium absorption.

Vitamin D stimulates intestinal absorption of calcium, regulates PTH release by the chief cells, and mediates PTH-stimulated bone reabsorption.

Calcitonin lowers calcium by targeting bone, renal, and GI losses.

The parathyroid gland has a sensitivity to ionized serum calcium changes due to the calcium-sensing receptor (CaSR), a 7-transmembrane receptor linked to G-protein with a large extracellular amino-terminal region.

Binding of calcium to the calcium-sensing receptor (CaSR) induces activation of phospholipase C and inhibition of PTH secretion.

A decrease in calcium stimulates the chief cells of the parathyroid gland to secrete PTH.

The loss of calcium-sensing receptor (CaSR) function leads to pathologic states, such as familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism.

In renal failure, calcium-sensing receptor (CaSR) agonists suppress the progression of hyperparathyroidism and parathyroid gland growth.

Homeostasis of calcium is maintained by an extracellular-to-intracellular gradient, which is largely due to abundant high-energy phosphates intracellularly.

Intracellular calcium regulates cyclic adenosine monophosphate (cAMP)–mediated messenger systems.

Extracellular calcium levels are maintained at 8.7-10.4 mg/dL.

Variations depend on serum pH, protein and anion levels, and calcium-regulating hormone function.

Patients with a decrease in total serum calcium may not have actual hypocalcemia, which is defined as a decrease in ionized calcium.

A reduction in total serum calcium can result from a decrease in albumin secondary to liver disease, nephrotic syndrome, or malnutrition.

Alkalemia induces tetany due to a decrease in ionized calcium, whereas acidemia is protective.

With renal failure who have hypocalcemia because rapid correction of acidemia or development of alkalemia may trigger tetany

Associated with hyperexcitability of neuromuscular cells with seizures, paresthesias an muscle spasms.

Physical signs that may be present inclde Trousseau’s sign, the spontaneous contraction of forearm muscles in response to blood pressure cuff around the upper arm inflated above the systolic blood pressure, and Chvostek’s sign-twitching of the facial muscles with tapping on the facial nerve as it exits the parotid gland.

In ESRD, low vitamin D levels, hyperphosphatemia, skeletal resistance to parathyroid hormone lead to hypocalcemia and renal osteodystrophy.

A predictor of death in geriatric patients and in patients with acute renal failure.

Falsely low calcium levels can occur with the use of gadolinium during MRI studies.

Electrocardiographic sings include prolonged QTc interval.

Severe abnormality can rarely be associated with myocardial hypocontractility and congestive heart failure.

Secondary changes from prolonged hypoparathyroidism can be associated with basal ganglia calcifications.

Seen in disorders of Vitamin D metabolism.

Seen in malabsorption syndromes such as short bowel syndrome or celiac sprue where calcium and vitamin D are malabsorbed.

Long term anticonvulsants such as phenytoins or Phenobarbital may lead to osteomalacia and hypocalcemia.

May be associated with vitamin D dependent rickets type I with a deficiency of enzyme vitamin D-1-alpha hydroxylase, or vitamin D dependent rickets type II with mutated vitamin D receptor.

Sepsis may be associated with mild hypocalcemia and confers a poor prognosis.

May be seen with elevated magnesium levels.

One of the most common causes is hypomagnesemia, often associated with alcoholism, impaired nutrition, intestinal malabsorption and cisplatin chemotherapy exposure.

Rapid rates of bone mineralization can lead to a net calcium entry into the skeleton and hypocalcemia, such as is seen in the hungry bone syndrome following parathyroidectomy.

May occur in patients with vitamin D deficiency with osteomalacia or rickets and unmineralized osteoid and treated with vitamin D with resultant use of calcium.

Rarely can occur in extensive osteoblastic metastases in breast or prostate cancer.

Patients undergoing long-term dialysis associated with increased risk in annual incidence of renal cancer and the risk increased with increasing duration of treatment.

In dialysis patients acquired renal cystic disease of kidneys appears to be the major factor in the increased risk of renal cancer.

Disorders that lead to hyperphosphatemia (renal failure, crush injuries, rhabdomyolysis, and tumor lysis syndrome) may cause hypocalcemia by exceeding the calcium-phosphate solubility product in serum.

May be caused by medications including mithramycin, bisphosphonates, calcitonin, fluoride intoxication, citrate in large volume transfusions, radiographic intravenous contrast agents and antiviral drug foscarnet.

Commonly caused by pancreatitis with formation of calcium free fatty acid soaps.

Pancreatitis releases lipase into peritoneum and retroperitoneum with auto digestion of retroperitoneal and omental fat with release of free fatty acids palmitrate, linoleate, and stearate from triglyceride fat stores.

Free fatty acids are negatively charged and chelate (bind) to extracellular calcium leading to insoluble calcium free fatty acid salts in the retroperitoneum and depletes calcium.

The treatment of hypocalcemia depends on the cause, severity, the presence of symptoms, and how rapidly the hypocalcemia developed.

The treatment of hypocalcemia depends on how rapidly the hypocalcemia developed.

Hypocalcemia generally results from another disease process.

Awareness of the diseases that cause hypocalcemia is important so that the cause can be identified and managed early.

Most hypocalcemic emergencies are mild and require only supportive treatment and further laboratory evaluation.

Severe hypocalcemia may result in seizures, tetany, refractory hypotension, or arrhythmias that require a more aggressive approach.

In the emergency department, magnesium and calcium are the medications necessary to treat hypocalcemic emergencies.

Rapid correction of symptomatic or severe hypocalcemia with cardiac arrhythmias or tetany with parenteral administration of calcium.

Administer 1-2 ampules 10% calcium gluconate in 50-100 mL of D5W over 5-10 minutes.

Calcium chloride 10% solution can deliver higher amounts of calcium, but it should be administered via a central line.

Serum calcium levels should be monitored every 4-6 hours to maintain serum calcium levels at 8-9 mg/dL.

In the presence of hypoalbuminemia ionized calcium levels should be monitored.

If patients have cardiac arrhythmias or are taking digoxin ECG monitoring during calcium replacement because of the possibilty of digitalis toxicity.

Oral calcium and vitamin D treatment should be initiated.

Treatment with calcium and vitamin D for 1-2 days prior to parathyroid surgery may help prevent the development of hypocalcemia.

Patients with hypoparathyroidism and pseudohypoparathyroidism can be managed with the oral calcium supplements.

With severe hypoparathyroidism, vitamin D treatment may be required, but because parathyroid deficiency impairs the conversion of vitamin D to calcitriol the most efficacious treatment is the addition of of calcitriol or 1-alpha-hydroxyvitamin D3.

Dialysis postparathyroidectomy patients may have hypocalcmia and oral calcium supplements and calcitriol should be provided.

Oral calcium preparations containing 1-2 g of elemental calcium per day can treat patients with a calcium deficiency.

Calcium chloride delivers 3 times more elemental calcium than calcium gluconate.

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