Calcium Imbalance

I. INTRODUCTION:

Calcium (Ca), an extracellular and intracellular cation, has a

normal serum range of 4.5 to 5.5 mEq/L or 9 to 11 mg/dl.
Approximately, 99% of the body’s calcium is in bone and teeth. The
other 1% is in tissue and intravascular fluid, of which half is bound to
protein, mostly albumin, and the remaining half is free, ionized
calcium. It has many functions in the body. It acts as a catalyst in the
transmission and conduction of nerve impulses and stimulates the
contraction of skeletal, smooth, and cardiac muscles. It maintains
normal cellular permeability. Increased serum calcium levels
decrease cellular permeability, and decreased serum calcium levels
increase cellular permeability. It promotes coagulation of blood in all
phases but mostly the prothrombin to thrombin phase. Calcium
promotes absorption and utilization of vitamin B12. Finally, it
promotes strong and durable bones and teeth. Calcium is excreted in
the urine and feces.

II. DISEASE ENTITY:

A. Hypocalcemia

• Cardiovascular complications: In severe cases, hypocalcemia

may lead to arrhythmias, hypotension, and heart failure. Some
patients may manifest digitalis insensitivity.
• Neurologic complications: In addition to acute seizures or tetany,
hypocalcemia may lead to basal ganglia calcification,
parkinsonism, hemiballisms, and choreoathetosis. Although
some patients with hypocalcemia may improve with treatment,
the calcification typically is not reversible.
• Hungry bone syndrome
Surgical correction of primary or secondary hyperparathyroidism
may be associated with severe hypocalcemia due to a rapid
increase in bone remodeling. Hypocalcemia results if the rate of
skeletal mineralization exceeds the rate of osteoclast-mediated
bone resorption. A less severe picture is also observed after
correction of thyrotoxicosis, after institution of vitamin D therapy
 for osteomalacia, and with tumors associated with bone
formation (eg, prostate, breast, leukemia).
• Acute pancreatitis
Pancreatitis can be associated with tetany and hypocalcemia. It
is caused primarily by precipitation of calcium soaps in the
abdominal cavity, but glucagon-stimulated calcitonin release
and decreased PTH secretion may play a role. When the
pancreas is damaged, free fatty acids are generated by the
action of pancreatic lipase. Insoluble calcium salts are present in
the pancreas, and the free fatty acids avidly chelate the salts,
resulting in calcium deposition in the retroperitoneum.

B. Hypercalcemia

• Hypercalcemia affects nearly every organ system in the body,

but it particularly affects the CNS and kidneys.
• Renal effects include nephrolithiasis from the hypercalciuria.
Distal renal tubular acidosis may be observed, and the increase
in urine pH and hypocitraturia also may contribute to stone
disease. Nephrogenic diabetes insipidus occurs from medullary
calcium deposition and inhibition of aquaporin-2, the arginine-
vasopressin–regulated water channel. Renal function may
decrease due to hypercalcemia-induced renal vasoconstriction or
if hypercalcemia is prolonged from calcium deposition
(nephrocalcinosis) and interstitial renal disease.
• High calcium levels also affect the conducting system of the
heart and cause cardiac arrhythmias. Calcium has a positive
inotropic effect. Hypercalcemia also causes hypertension,
presumably from renal dysfunction and direct vasoconstriction.
• The GI manifestations of hypercalcemia include anorexia,
nausea, vomiting, and constipation. Prolonged hypercalcemia
tends to cause high gastrin levels, which may contribute to
peptic ulcer disease and may lead to pancreatitis or the
deposition of calcium in any soft tissue. This deposition of
calcium is especially prevalent if phosphorous levels also are
elevated, as in renal failure.

III. PATHOPHYSIOLOGY
 A. Hypocalcemia ( serum calcium level below 4.5 mEq/L or 8.5
mg/dl )

A lack of PTH results in inactivity of osteoclasts and a

consequent fall in serum calcium levels. Nerve fibers become more
and more excitable and may discharge spontaneously, causing
muscles to twitch and to go into spasms or even tetany. Spasms of
the muscles of the larynx interfere with respiration and may lead to
death. During hypocalcemia, the bone is stimulated to release
calcium, which makes the bone osteoporotic and subject to fracture.
Hypocalcemia increases capillary permeability; causes neuromuscular
excitability of skeletal, smooth, and cardiac muscles; and decreases
blood coagulation, which results in bleeding. Severe hypocalcemia
causes neuromuscular excitability that result in tetany. If it is
untreated, convulsions and death can occur. Acute hypocalcemia
may cause cardiac insufficiency and cardiac dysrhythmias.

B. Hypercalcemia ( serum level over 5.5 mEq/L or 11 mg/dL )

Because calcium levels are increased, there is a lesser

gradient between the cell and the serum. There is also an increased
amount of calcium in the cell. Therefore, the threshold becomes
more difficult to achieve and the cell membrane becomes refractory
to depolarization. As a result, cardiac and smooth muscle activity is
decreased. Calcium in the bloodstream impairs renal function and it
precipitates as a salt, forming renal stones. Some cancer tumors
destroy the bone, whereas others such as lung and breast cancers
cause an ectopic PTH production. Hypophosphatemia is a
complication of excessive PTH production that promotes calcium
retention. A shortened QT segment and depressed T waves may be
seen on ECG.

IV. MEDICAL MANAGEMENT ( Diagnostic Tests ):

A. Hypocalcemia
 Medical management is focused on determining and
correcting the cause of the hypocalcemia. Other medical
management is dictated by the level of the serum calcium.

Imaging Studies

• Skeletal x-rays
•
o Disorders associated with rickets or osteomalacia present
with the pathognomonic Looser zones, better observed in
the pubic ramus, upper femoral bone, and ribs.
o Osteoblastic metastases from certain tumors (eg, breast,
prostate, lung) can cause hypocalcemia.
• CT scan of the head may show basal ganglia calcification and
extrapyramidal neurologic symptoms (in idiopathic
hypoparathyroidism).

Other Tests

• Electrocardiogram (ECG): Hypocalcemia leads to a prolonged QT

interval and severe ST abnormalities (see Media file 1).

Procedures

• Bone biopsy: If the diagnosis of osteomalacia is suspected, a bone biopsy can determine the
final diagnosis.
• Parathyroidectomy (subtotal or total) may be indicated in certain
patients with severe secondary hyperparathyroidism and renal
osteodystrophy

B. Hypercalcemia

Imaging Studies

• Chest radiographs always should be performed to help rule out

lung cancer or sarcoidosis. Other radiographs should be
 considered to help evaluate for possible malignancies,
metastases, or Paget disease.
• Mammograms should be considered to help rule out breast
cancer, and CT scan and ultrasound should be considered to
help rule out renal cancer.
• When a biochemical diagnosis of primary hyperparathyroidism is
made, CT scan, ultrasound, MRI, and radionuclide imaging of the
parathyroid gland may be helpful to assist with preoperative
localization.

Other Tests

• Miscellaneous
o Peripheral smear
o Serum and urine immunofixation electrophoresis

Procedures

• Tissue histology
o Biopsy of solid tumor
o Biopsy of bone marrow

V. MEDICATION:

A. Hypocalcemia

Drug Category: Electrolytes

Restores serum calcium levels. Calcium chloride delivers 3 times

more elemental calcium than calcium gluconate.

Drug Name Calcium chloride

Description Ventricular fibrillation not associated with
hyperkalemia, digitalis toxicity, hypercalcemia, renal
insufficiency, or cardiac disease. Preferred when
patient is in cardiac arrest and in other serious cases.
Ten mL of calcium chloride 10% (1 g/10 mL) contain
 272 mg of elemental calcium.
Documented hypersensitivity; ventricular fibrillation
Contraindica
not associated with hyperkalemia; digitalis toxicity;
tions
hypercalcemia; renal insufficiency; cardiac disease
Coadministration with digoxin may cause arrhythmias;
with thiazides, may induce hypercalcemia; may
antagonize effects of calcium channel blockers,
Interactions
especially verapamil; decreases effects of atenolol,
tetracyclines, salicylates, fluoroquinolones, and sodium
polystyrene sulfonate
C - Fetal risk revealed in studies in animals but not
Pregnancy established or not studied in humans; may use if
benefits outweigh risk to fetus

Drug Name Calcium carbonate (Oystercal, Caltrate)

Indicated to restore and maintain normocalcemia when
Description hypocalcemia is not severe enough to warrant rapid
replacement.
Documented hypersensitivity; renal calculi;
Contraindicat hypercalcemia; hypophosphatemia; renal or cardiac
ions disease; digitalis toxicity
May decrease effects of tetracyclines, atenolol,
salicylates, iron salts, and fluoroquinolones; large
Interactions intakes of dietary fiber may decrease calcium
absorption and levels; calcium potentiates digitalis
effects
C - Fetal risk revealed in studies in animals but not
Pregnancy established or not studied in humans; may use if
benefits outweigh risk to fetus

Drug Category: Vitamins

Restore calcium levels in conditions associated with vitamin D

deficiency. Vitamin D helps control hyperparathyroidism in patients
with chronic renal failure and end-stage renal disease.

Drug Name Calcitriol (Calcijex, Rocaltrol)

 Increases calcium levels by promoting calcium
absorption in intestines and calcium retention in
Description kidneys. To prevent hyperparathyroidism, patients on
dialysis may require higher doses, >1 mcg/d divided 2-
3 times per wk.
Contraindicat Documented hypersensitivity; hypercalcemia;
ions malabsorption syndrome; hyperphosphatemia
Cholestyramine and colestipol decrease absorption of
Interactions calcitriol; magnesium-containing antacids and thiazide
diuretics can increase calcitriol effects
C - Fetal risk revealed in studies in animals but not
Pregnancy established or not studied in humans; may use if
benefits outweigh risk to fetus

B. Hypercalcemia

Drug Category: Bisphosphonates

Inhibit bone reabsorption.

Drug Name Pamidronate (Aredia)

Used after initial hydration to inhibit bone reabsorption
Description and maintain low serum calcium levels, especially in
hypercalcemia of malignancy and Paget disease.
Contraindica
Documented hypersensitivity; hypocalcemia
tions
Interactions None reported
Monitor hypercalcemia-related parameters (eg, serum
levels of calcium, phosphate, magnesium, and
potassium) once treatment begins; adequate intake of
calcium and vitamin D are necessary to prevent severe
Precautions
hypocalcemia; caution when administering
bisphosphonates in patients with active upper GI
problems; do not coadminister with alendronate for
osteoporosis in postmenopausal women
Drug Category: Antineoplastic drugs

Some agents in this drug class can reduce bone turnover.

Drug Name Gallium nitrate (Ganite)

Available in the United States. Use should be limited to
Description those with extensive experience in this field (ie,
oncologists).
Contraindica
Documented hypersensitivity; renal failure
tions
Nephrotoxic effects increase when administered with
Interactions
amphotericin B or aminoglycosides
Precautions Caution in renal failure

Drug Category: Antidote, hypercalcemia agents

Inhibit bone resorption and increase renal calcium excretion.

Drug Name Calcitonin (Miacalcin, Osteocalcin)

Lowers elevated serum calcium in patients with
multiple myeloma, carcinoma, or primary
hyperparathyroidism. Expect higher response when
serum calcium levels are high.
Description Onset of action is approximately 2 h following
injection, and activity lasts for 6-8 h. May lower
calcium levels for 5-8 d by approximately 9% if given
q12h. IM route is preferred at multiple injection sites
with dose > 2 mL.
Contraindicat
Documented hypersensitivity
ions
Interactions None reported
Hypocalcemia may occur; examine urine sediment
Precautions
during prolonged therapy

Drug Category: Glucocorticoids

Inhibit cytokine release and have a direct cytolytic effect on some

tumor cells.
 Drug Name Prednisone (Deltasone, Orasone, Sterapred)
Immunosuppressant for treatment of autoimmune
disorders; may decrease inflammation by reversing
Description increased capillary permeability and suppressing PMN
activity. Stabilizes lysosomal membranes and
suppresses lymphocytes and antibody production.
Documented hypersensitivity; viral infection, peptic
Contraindicat ulcer disease, hepatic dysfunction, connective tissue
ions infections, and fungal or tubercular skin infections; GI
disease
Coadministration with estrogens may decrease
clearance; concurrent use with digoxin may cause
digitalis toxicity secondary to hypokalemia;
Interactions phenobarbital, phenytoin, and rifampin may increase
metabolism of glucocorticoids (consider increasing
maintenance dose); monitor for hypokalemia with
coadministration of diuretics
Abrupt discontinuation of glucocorticoids may cause
adrenal crisis; hyperglycemia, edema, osteonecrosis,
myopathy, peptic ulcer disease, hypokalemia,
Precautions
osteoporosis, euphoria, psychosis, myasthenia gravis,
growth suppression, and infections may occur with
glucocorticoid use

Drug Category: Minerals

Phosphate inhibits calcium absorption and promotes calcium

deposition. Theorized to help bind dietary calcium, thus rendering it
an unabsorbable calcium-phosphorous product, but used rarely.

Drug Name Potassium phosphate (Neutra-Phos-K)

Increases urinary pyrophosphate and complexes with
calcium, thus decreasing urinary calcium level, while
pyridoxine results in a reduction of urinary oxalate
Description excretion. All dosage forms must be mixed in 6-8 oz of
water. Never give IV. Never give if renal function is
abnormal or if serum phosphorous levels are > 3
mg/dL.
Contraindicat Abnormal renal function, renal failure, serum
ions phosphorous >4.5 mg/dL; IV administration
Magnesium-containing and aluminum-containing
antacids or sucralfate can act as phosphate binders
Interactions and decrease serum phosphate levels; potassium-
sparing diuretics, ACE inhibitors, and salt substitutes
may increase serum phosphate levels
Caution in patients with renal insufficiency and
metabolic alkalosis; admixture of phosphate and
Precautions
calcium in IV fluids can result in calcium phosphate
precipitation

VI. NURSING MANAGEMENT:

A. Hypocalcemia

The nurse should have a high index of suspicion for those

clients at risk for hypocalcemia and present with clinical
manifestations. If neuromuscular and cardiac symptoms are present,
the hypocalcemic state is usually severe. Assessing the medications
and diet of the client is taking is important. If the client is taking a
digitalis preparation, administration of calcium will enhance the
action of digitalis and may cause digitalis toxicity. The client’s diet
may also give clues to hypocalcemia due to malnutrition or lack of
calcium intake.
Two tests used to check for increased neuromuscular
excitability and tetany are the Trousseau’s sign and Chvostek’s sign.
The Trousseau’s sign is carpopedal spasm. It is best elicited by
inflating a blood pressure cuff on the upper arm for 1-5 minutes,
constricting circulation. A positive test result is carpopedal spasm.
The Chvostek’s sign is spasm of the muscles innervated by the facial
nerve. It is best determined by tapping the client’s face lightly below
the temple. Spasm of the face, lip or nose would indicate a positive
for tetany.

B. Hypercalcemia
 The nurse should have a high index of suspicion for those
clients at risk for hypercalcemia or with early symptoms of this
disorder. When the nurse notes an elevated serum calcium level, the
nurse should assess the client for signs and symptoms of
neuromuscular and cardiac changes associated with hypercalcemia.
An accurate nursing history may identify factors such as excessive
use of calcium supplements or calcium-containing antacids that could
cause a mild to moderate hypercalcemia. A drug history is important
for determining whether the medications the client is taking could be
affected by the hypercalcemic state. For example, an increased
calcium level enhances the action of digitoxin; thus, digitalis toxicity
may result.
The client’s hydration status should be assessed for fluid
volume depletion caused by hypercalcemia. ECG changes and the
state of the client’s sensorium should be reported.