Hypocalcemia

Background

Hypocalcemia is frequently encountered in patients who are hospitalized. Presentations

vary widely, from asymptomatic to life-threatening situations. A 70-kg person has
approximately 1.2 kg of calcium in the body, most of which is stored as hydroxyapatite in
bones (>99%). Less than 1% (5-6 g) of this calcium is located in the intracellular and
extracellular compartments, with only 1.3 g located extracellularly. The total calcium
concentration in the plasma is 4.5-5.1 mEq/L (9-10.2 mg/dL). Fifty percent of plasma
calcium is ionized, 40% is bound to proteins (90% of which binds to albumin), and 10%
circulates bound to anions (eg, phosphate, carbonate, citrate, lactate, sulfate).

At a plasma pH of 7.4, each gram of albumin binds 0.8 mg/dL of calcium. This bond is
dependent on the carboxyl groups of albumin and is highly dependent on pH. Acute
acidemia decreases calcium binding to albumin, whereas alkalemia increases binding,
which decreases ionized calcium. Clinical signs and symptoms are observed only with
decreases in ionized calcium concentration (normally 4.5-5.5 mg/dL).

Pathophysiology

Ionized calcium is the necessary plasma fraction for normal physiologic processes. In the
neuromuscular system, ionized calcium levels facilitate nerve conduction, muscle
contraction, and muscle relaxation. Calcium is necessary for bone mineralization and is
an important cofactor for hormonal secretion in endocrine organs. At the cellular level,
calcium is an important regulator of ion transport and membrane integrity. The calcium
turnover is estimated at 10-20 mEq/d. Approximately 500 mg of calcium are removed
from the bones daily and replaced by an equal amount. Normally, the amount of calcium
absorbed by the intestines is matched by urinary calcium excretion. Despite these
enormous fluxes of calcium, the levels of ionized calcium remain stable because of the
rigid control of parathyroid hormone (PTH) and vitamin D levels. Normocalcemia
requires PTH and normal target-organ response to PTH. The parathyroid gland has a
remarkable sensitivity to ionized serum calcium changes.

These changes are recognized by 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 CaSR induces activation of phospholipase C and
inhibition of PTH secretion. On the other hand, a slight decrease in calcium stimulates the
chief cells of the parathyroid gland to secrete PTH. CaSR is crucial in PTH secretion. A
loss of CaSR function leads to pathological states, such as familial hypocalciuric
hypercalcemia and neonatal severe hyperparathyroidism. In renal failure, CaSR agonists
suppress the progression of hyperparathyroidism and parathyroid gland growth. PTH
stimulates osteoclastic bone reabsorption and distal tubular calcium reabsorption and
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. Patients with a decrease in total
serum calcium may not have "true" 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. Hypocalcemia
causes neuromuscular irritability and tetany. Alkalemia induces tetany due to a decrease
in ionized calcium, whereas acidemia is protective. This pathophysiology is important in
patients with renal failure who have hypocalcemia because rapid correction of acidemia
or development of alkalemia may trigger tetany.

Medical Care

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

• Acute hypocalcemia
•
o Promptly correct symptomatic or severe hypocalcemia with cardiac
arrhythmias or tetany with parenteral administration of calcium salts.
o
 Administer 1-2 ampules 10% calcium gluconate (93 mg/10 mL) in
50-100 mL of D5W over 5-10 minutes. Calcium chloride 10%
solution (273 mg/10-mL ampule) delivers higher amounts of
calcium and is advantageous when rapid correction is needed,
but it should be administered via central venous access.
 Measure serum calcium every 4-6 hours to maintain serum calcium
levels at 8-9 mg/dL. If low albumin is also present, ionized
calcium should be monitored.
o Patients with cardiac arrhythmias or patients on digoxin therapy need
continuous ECG monitoring during calcium replacement because calcium
potentiates digitalis toxicity.
o Identify and treat the cause of hypocalcemia and taper the infusion.
o Start oral calcium and vitamin D treatment early. Patients with
postparathyroidectomy hungry bone disease, especially those with osteitis
fibrosa cystica, can present with a dramatic picture of hypocalcemia.
o Treatment with calcium and vitamin D for 1-2 days prior to parathyroid
surgery may help prevent the development of severe hypocalcemia.
• Chronic hypocalcemia: Treatment of chronic hypocalcemia depends on the cause
of the disorder.
•
o PTH deficiency: Patients with hypoparathyroidism and
pseudohypoparathyroidism can be managed initially with the oral
administration of calcium supplements. The hypercalcemic effects of
thiazide diuretics may offer some additional benefits. In patients with
severe hypoparathyroidism, vitamin D treatment may be required;
however, remember that PTH deficiency impairs the conversion of
 vitamin D to calcitriol. Therefore, the most efficient treatment is the
addition of 0.5-2 mcg of calcitriol or 1-alpha-hydroxyvitamin D3.
o Hypocalcemia in patients on dialysis: Most patients on hemodialysis will
be hypercalcemic. However, postparathyroidectomy, patients may have
considerable difficulty in maintaining appropriate calcium levels. These
levels can be managed several ways. First, oral calcium supplements
should be provided. They must be given between meals; otherwise, they
will primarily act as phosphate binders. Active vitamin D administration
(calcitriol) enhances the absorption of calcium. Finally, the calcium in the
dialysate bath can be increased.
o Nutritional vitamin D deficiency from lack of sunlight exposure or poor
oral intake of vitamin D: Ultraviolet light or sunlight exposure can treat
these patients. Treat nutritional rickets with vitamin D2. Oral calcium
preparations containing 1-2 g of elemental calcium per day can treat
patients with a calcium deficiency. For infants who are breastfed, adjust
the dose to 30 mg/kg/d. Calcitriol may be used, but it has the
disadvantages of a higher price and the possibility of producing
hypervitaminosis D with hypercalcemia.

Surgical Care

Parathyroidectomy (subtotal or total) may be indicated in certain patients with severe

secondary hyperparathyroidism and renal osteodystrophy.

Diet

• An increase in dietary calcium to greater than 1 g/d is an important part of the

treatment of chronic hypocalcemia, particularly in cases of vitamin D deficiency.
• In patients with hypocalcemia and chronic renal failure, the dietary intake of
phosphate should be lowered to 400-800 mg/d to prevent hyperphosphatemia.

Further Inpatient Care

• After correction of serum calcium, initiate a workup to help diagnose the cause of
hypocalcemia.

Further Outpatient Care

• After determining the cause for hypocalcemia, direct the treatment at preventing
further episodes of hypocalcemia and avoiding the complications of chronic
hypocalcemia.
• Following parathyroidectomy, patients should be seen in 5-7 days for follow-up
determination of serum calcium.

In/Out Patient Meds

 • Patients with hypocalcemia due to resistance to PTH generally will require long-
term therapy with vitamin D and calcium supplementation.
• Patients with hypocalcemia associated with chronic renal failure often require
phosphate binders and vitamin D supplementation.

Transfer

• Patients with hypocalcemia and renal failure may require transfer to a facility with
hemodialysis available.

Complications

• Complications of chronic hypocalcemia predominantly are those of bone disease.

•
o Osteomalacia and rickets result from vitamin D deficiency.
o Osteitis fibrosis cystica and osteomalacia occur in patients with
hypercalcemia and secondary hyperparathyroidism.

Prognosis

• Prognosis usually is favorable and depends on the cause and duration of

hypocalcemia.

Patient Education

• The primary component of patient education involves dietary instruction in

patients with hypocalcemia.
• Patients with chronic hypocalcemia should be informed about the early symptoms
of hypocalcemia, such as paresthesias and muscle weakness, so they can obtain
care prior to developing more severe symptoms.

Causes of Hypocalcemia (Serum levels below 4.5mEq/l or 9 mg./dL)

• Inadequate calcium intake,Vitamin D, or lactase deficiency, chrones disease or other

malabsorptive disorders
• para-thyroid hormone deficiency, renal disease (calcium is excreted - phosphorus is
retained)

More Causes of Hypocalcemia

• some cancers, massive blood transfusions (they put citrate in the blood to preserve it, the
citrate binds with calcium so it is not usable in the body), abuse of laxatives or enemas
• Some drugs (glucocorticoids, heparin, loop diuretics,glucagon)
 Symptoms of Hypocalcemia

• Tingling of hands, fingers, feet, or around the mouth

• laryngeal spasm, bleeding tendencies
• Tetany - grimacing, muscle twitching, cramping, hyperactive reflexes (Chvostek’s sign -
tapping the facial nerve causes facial twitch)

Symptoms of hypocalcemia

• severe flexion of the wrist and ankle joints when circulation is interrupted for a few
minutes(Trousseau’s sign) - Calcium channels are too open letting impulses go through
too fast
• diarrhea (intestinal motility), restlessness, lack of concentration.

Treatment of Hypocalcemia

• Calcium gluconate or calcium chloride IV (causes sloughing if infiltrates)

• Oral calcium suppliments (Tums, calcium lactate)
• Increased calcium in diet - milk, cheese, green leafy veggies

Treatment of Hypocalcemia

• pre-manapausal women should have 1000mg/day - post 1500 to prevent osteoporosis.

Must have Vit D to absorb calcium (added to milk)

Your patient who has serum calcium of 8.4 states that she hates milk

• what could you suggest to help her improve the serum calcium level (you cannot order
medication of any kind)

Nursing Process

• Take a history for hypoparathyroidism, radiation or injury to the neck,overuse of laxatives

or anticids, dietary history, use of vitamin D suppliments or calcium medication
• Assess for S/S of hypocalcemia

Possible nursing diagnoses

• Risk for injury related to tetany secondary to hypocalcemia

 • Altered nutrition less than body requirements related to inadequate intake of calcium or
vitamin D
• avoid use laxatives (especially ones containing phosphates) or antacids containing
magnesium

hypercalcemia
Background

Hypercalcemia is a disorder that most commonly results from malignancy or primary

hyperparathyroidism. Other causes of elevated calcium are less common and usually are
not considered until malignancy and parathyroid disease are ruled out.

Hypercalcemic crisis does not have an exact definition, although marked elevation of
serum calcium, usually more than 14 mg/dL, is associated with acute signs and symptoms
of hypercalcemia. Treatment of the elevated calcium level may resolve the crisis.

The reference range of serum calcium levels is 8.7-10.4 mg/dL, with somewhat higher
levels present in children. Approximately 40% of the calcium is bound to protein,
primarily albumin, while 50% is ionized and is in physiologic active form. The remaining
10% is complexed to anions.

Pathophysiology

Plasma calcium is maintained within the reference range by a complex interplay of 3

major hormones, parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (ie, calcitriol),
and calcitonin. These 3 hormones act primarily at bone, kidney, and small intestine sites
to maintain appropriate calcium levels.

Calcium enters the body through the small intestine and eventually is excreted via the
kidney. Bone can act as a storage depot. This entire system is controlled through a
feedback loop; individual hormones respond as needed to increase or decrease the serum
calcium concentration.

For hypercalcemia to develop, the normal calcium regulation system must be

overwhelmed by an excess of PTH, calcitriol, some other serum factor that can mimic
these hormones, or a huge calcium load.

Hypercalcemia can result from a multitude of disorders. The causes are divided into
PTH-mediated hypercalcemia and non–PTH-mediated hypercalcemia.

PTH-mediated hypercalcemia

Primary hyperparathyroidism originally was the disease of "stones, bones, and abdominal
groans." In most primary hyperparathyroidism cases, the calcium elevation is caused by
increased intestinal calcium absorption. This is mediated by the PTH-induced calcitriol
synthesis that enhances calcium absorption. The increase in serum calcium results in an
increase in calcium filtration at the kidney. Because of PTH-mediated absorption of
calcium at the distal tubule, less calcium is excreted than might be expected. In PTH-
mediated hypercalcemia, bones do not play an active role because most of the PTH-
mediated osteoclast activity that breaks down bone is offset by hypercalcemic-induced
bone deposition. Hypercalcemia of this disorder may remain mild for long periods
because some parathyroid adenomas respond to the feedback generated by the elevated
calcium levels.

Non–PTH-mediated hypercalcemia

Hypercalcemia associated with malignancy commonly is the result of multiple myeloma,

breast, or lung cancer and is caused by increased osteoclastic activity within the bone.
Granulomatous disorders with high levels of calcitriol may be found in patients with
sarcoidosis, berylliosis, tuberculosis, leprosy, coccidioidomycosis, and histoplasmosis.
Iatrogenic disorders of calcium levels may increase secondary to the ingestion of many
medications.

Prehospital Care

Prehospital care is primarily supportive with management of the ABCs. If a patient has a
history of hypercalcemia and displays evidence of acute hypercalcemia, immediately
begin IV hydration.

Emergency Department Care

The treatment of hypercalcemia depends on the level, the chronicity, and the underlying
cause of the problem. In mild-to-moderate elevations of calcium, few treatment options
may be available in the ED. A physical evaluation to help delineate the source of the
elevation is always appropriate, as is a subsequent timely follow-up visit.

• Initial goals of treatment

•
o Stabilization and reduction of the calcium level
o Adequate hydration
o Increased urinary calcium excretion
o Inhibition of osteoclast activity in the bone
o Discontinuation of pharmacologic agents associated with hypercalcemia
o Treatment of the underlying cause (when possible)
• The initial step in the care of severely hypercalcemic patients is hydration with
saline. Hydration helps decrease the calcium level through dilution. The
expansion of extracellular volume also increases the renal calcium clearance. The
rate of fluid therapy is based upon the following:
•
o Degree of hypercalcemia
o Severity of dehydration
 o Ability of the patient to tolerate rehydration - Vigilance to prevent volume
overload is critical.
o Hydration is ineffective in patients with kidney failure because diuresis is
impossible. Dialysis is necessary to correct hypercalcemia in patients with
renal failure.
• Loop diuretics
•
o A loop diuretic (eg, furosemide) may be used with hydration to increase
calcium excretion. This may also prevent volume overload during therapy.
o In contrast to loop diuretics, avoid thiazide diuretics because they increase
the reabsorption of calcium.
• Bisphosphates - These agents will inhibit osteoclast activity for up to a month.

Consultations

• Patients with renal failure or heart failure may not be able to tolerate fluid
hydration or some of the other medications. Patients in this group who present
with severe elevations of calcium may require urgent dialysis. Consult a
nephrologist immediately in such cases.
• Patients with primary hyperparathyroidism may require surgery to eliminate the
condition, but surgery usually does not need to be performed on an urgent basis.
• Patients with malignancy may require surgery, chemotherapy, or radiation
treatment. Appropriate consultation should be undertaken.

Further Inpatient Care

• Serum calcium level generally responds to fluids and Lasix; however, this therapy
has no effect on the principle pathologic process causing hypercalcemia.
Additional therapy must be added to the temporizing treatment described above.
• Treatment of the underlying disease must be addressed.

Further Outpatient Care

• Patients with primary hyperparathyroidism who present with symptoms of severe

or moderate elevations of calcium levels should be referred for
parathyroidectomy. This referral may be urgent, depending on the severity of the
hypercalcemia.
• Patients with mild-to-moderate elevations of calcium who have no symptoms may
be evaluated on an outpatient basis and usually are treated medically. For those
patients with malignancy as the cause of their hypercalcemia, a cure may not be
possible.
• The ideal scenario finds a treatable underlying cause for hypercalcemia and
allows the physician to attend to this primary process. If this is accomplished, the
patient may not need therapy for the hypercalcemia itself.
• The drug regimen most appropriate for each individual depends on the cause of
the elevation and usually is not managed by the ED physician.
 • Patients may require ongoing treatment for calcium elevation.
• This type of treatment can be frustrating and difficult, and it is not always
successful.

Transfer

• Transfer may be considered in a number of situations.

•
o If a patient presents with severe hypercalcemia and renal failure,
emergency dialysis is necessary. Consider transfer if this is unavailable at
the initial treatment center.
o If no intensivist or physician familiar with the inpatient treatment of
hypercalcemia is available, consider transferring patients with normal
kidney function who are being treated for severe hypercalcemia.

Deterrence/Prevention

• Avoid prolonged bedrest for patients known to have rapid bone turnover.
• Consider elective surgical procedures for patients with Paget disease after therapy
has been initiated for calcium elevation. Mobilize patients as quickly as possible
to minimize bone loss.
• Worsening hypercalcemia is common in patients with known metastatic disease
who are too ill to ambulate. This should be anticipated and treated before the
patient becomes symptomatic.
• Patients at risk for hypercalcemia should have scheduled appointments with
ongoing evaluation to monitor for development or progression of the disease.
• Avoid salt restriction, diuretics, and other causes of volume depletion and
dehydration in patients with active or potential hypercalcemia.

Prognosis

• The prognosis of patients with hypercalcemia depends upon the etiology of the
elevation.
•
o Prognosis is very poor with malignancy that has progressed into
development of hypercalcemia.
o Prognosis is excellent when the underlying cause is treatable and treatment
is initiated promptly.

Causes of Hypercalcemia (Serum levels over 10.5mg/dL)

• Excessive intake of Vitamin D

• Excessive intake of milk or alkaline antacids
• hyperthyroidism or some cancers
• immobility or reduced renal function
• thiazide diuretics (HTZ)
 Symptoms of Hypercalcemia

• Decreased neuromuscular irritability - muscle weakness, lack of coordination, absent

deep tendon reflexes, slurred speech, confusion, lethargy, and impaired memory,
depression
• Gastrointestinal problems: decreased peristalsis, anorexia, nausea, vomiting, and
constipation,
• puritis (itching), kidney stones and bone pain

Treatment of Hypercalcimia

• IV normal saline, loop diuretics

• treat the cause - stop taking too much vitamin D, diagnose and treat the hyperthyroidism
or cancer

Your patient has a serum calcium of 10.6

• name 4 behaviors that if present could indicate hypercalcemia

Nursing Process

• Obtain history of health problems associated with hypercalcemia, cancer,

hyperparathyroidism, immobility, hyperthyroidism, and renal failure, Use of medications
(glucocorticoids,thiazide diuretics, calcium or vit D supliments & antacids. foods
containing calcium.
• Assess for S/S or hypercalcemia

Possible Nursing Diagnoses

• Constipation related to decreased intestinal motility

• Risk for injury related to muscle weakness incoordination, memory lapses and confusion

Treatment Return to top

Treatment is directed at the cause of hypercalcemia whenever possible. In cases of

hyperparathyroidism, surgery may be needed to remove the abnormal parathyroid gland
and cure the hypercalcemia.

If your hypercalcemia is mild and caused by primary hyperparathyroidism, your health

care provider will follow you closely over time.
Severe hypercalcemia that causes symptoms and requires a hospital stay is treated with
the following:

• Calcitonin
• Dialysis
• Drugs that stop bone breakdown and absorption by the body, such as pamidronate
or etidronate (bisphosphonates)
• Fluids through a vein (intravenous fluids)
• Glucocorticoids (steroids)

Outlook (Prognosis) Return to top

How well you do depends on the cause of hypercalcemia. Patients with mild
hyperparathyroidism or hypercalcemia with a treatable cause (for example, primary
hyperparathyroidism or dietary hypervitaminosis D) may not have complications.

Patients with hypercalcemia due to conditions such as cancer or granulomatous disease

may not do well due to the disease itself, rather than to the hypercalcemia.

Possible Complications Return to top

Gastrointestinal

• Hypertension
• Pancreatitis
• Peptic ulcer disease

Kidney

• Calcium deposits in the kidney (nephrocalcinosis)

• Dehydration
• Kidney failure
• Kidney stones

Psychological

• Depression
• Difficulty concentrating or thinking

Skeletal

• Bone cysts
• Fractures
• Osteoporosis

The complications of long-term hypercalcemia are uncommon today.

When to Contact a Medical Professional Return to top

Contact your physician or health care provider if you have:

• Family history of hypercalcemia

• Family history of hyperparathyroidism
• Symptoms of hypercalcemia

Prevention Return to top

Most causes of hypercalcemia cannot be prevented. Women over the age of 50 should see
their health care provider regularly and have their blood calcium screened periodically.

You can avoid hypercalcemia from calcium and vitamin D supplements by contacting
your health care provider for advice if you are taking supplements without a prescription.