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MLAB 2401: Clinical Chemistry�Keri Brophy-Martinez

Diseases of Mineral and Bone

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Hypercalcemia

Blood calcium levels above expected range
Caused by:

Malignancy
Primary Hyperparathyroidism
Renal Failure
Multiple myeloma

Hypercalcemia is the state of blood calcium levels above the expected range. Hypercalcemia is usually related to various endocrine and organ physiology factors. Hypercalcemia is a concern because one of the two main causes is malignancy or primary hyperparathyroidism. In primary hyperparathyroidism, the body secretes excess PTH, which in turn increases the blood calcium levels due to the action of PTH on bone and on the kidneys. PTH stimulates the bone to increase osteoclastic activity, which releases calcium. PTH also acts on the kidney to absorb more calcium. Again the net effect is an increase on calcium levels.

If the hypercalcemia is associated with malignancy, usually the cause of the increased calcium is a PTH-related peptide produced by the tumor which binds to PTH receptors and causes the increased calcium levels. If you recall from the Fall semester, in patients with Multiple Myeloma- the abnormal plasma cells result in lytic bone lesions. As calcium is released from the bone- blood calcium increases. In renal failure, if the kidneys are not operating correctly, increased amounts of calcium can be taken up rather than excreted.

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Clinical Symptoms of Hypercalcemia

CNS

Disorientation
Lethargy
Confusion
Depression

GI

Constipation
Nausea
Vomiting

Renal

Kidney stones

Skeletal

Increased risk of fractures

Cardiovascular

Hypertension

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Hypocalcemia

Blood calcium levels below the expected range
Caused by:

Hypoparathyroidism
Decreased vitamin D

Inadequate diet
Malabsorption

Hypo/Hypermagnesemia
Decreased calcium intake

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Clinical Symptoms Of Hypocalcemia

Neuromuscular irritability

Muscle cramps
Seizures
Tetany

Cardiac irregularities

Arrhythmia

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Hypermagnesemia

Increased magnesium
Caused by:

Decreased Excretion	Acute/chronic renal failure Endocrine disorders
Increased Intake	Antacids Enemas
Miscellaneous	Bone cancers Severe dehydration

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Clinical Symptoms of Hypermagnesemia

Cardiovascular	Hypotension Bradycardia
Neuromuscular	Decreased reflexes Respiratory depression
Dermatologic	Flushing
GI	Nausea Vomiting
Metabolic	Warm skin Hypocalcemia

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Hypomagnesemia

Decrease in the blood level of magnesium
Caused by:

Reduced Intake
Decreased Absorption
Increased Excretion

RENAL
ENDOCRINE
DRUG INDUCED

Miscellaneous

Pregnancy

Hypomagnesemia is most frequently encountered in hospitalized individuals in ICUs or those receiving diuretic therapy. These patients usually have an overall tissue depletion of magnesium as a result of severe disease or loss which leads to the low serum values. Although there are many causes of hypomagnesemia, they can be grouped into four general categories. Reduced intake can be due to a magnesium deficient diet or IV therapy which can result in loss of the ion. Various GI disorders can cause a decreased absorption by the intestine, which can result in excess loss of magnesium via the feces. Magnesium loss due to increased excretion by way of the urine can occur as the result of various renal and endocrine disorders or the effects of various drugs on the kidneys. Miscellaneous causes include excess lactation and pregnancy.

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Clinical Symptoms of Hypomagnesemia

Hypertension
Arrhythmia

Depression
Agitation
Psychosis

Cardiovascular

Psychiatric

Neuromuscular

Weakness
Cramps
Tetany

Metabolic

Hypokalemia
Hypocalcemia
Hypophosphatemia
Hypotremia

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Hyperphosphatemia

Elevated levels of phosphate in the blood
Caused by:

Decreased renal excretion

Acute/chronic renal failure

Increased intake

Oral, rectal, IV administration

Increased cellular breakdown

Neoplasms, intravascular hemolysis

Clinical symptoms

No direct symptoms

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Hypophosphatemia

Decreased level of blood phosphate
Caused by:

Increased renal excretion
Hyperparathyroidism
Decreased intestinal absorption

Vitamin D deficiency
Use of antacids

Sepsis

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Clinical Symptoms of Hypophosphatemia

Present once phosphorus levels decrease to one-half the lower limit of normal.
Weakness
Dizziness
Respiratory Failure
Impairment of cardiac contractility

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Parathyroid Disorders

Hyperparathyroidism

Causes

Benign adenoma
Hyperplasia of tissue in response to chronic calcium loss
Secretion of PTH from malignant non-endocrine tumor

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Hyperparathyroidism

Clinical Signs & Symptoms

Increased PTH
Increased urine and serum calcium
Decreased serum phosphorous
Increased urine phosphorous
Kidney problems (stones)
Bone problems (demineralization)

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Hypoparathyroidism

Root Causes

Primary

Idiopathic

Secondary

Thyroid/ parathyroid surgery
Autoimmune destruction of parathyroid tissue

Clinical Signs & Symptoms

Decrease PTH
Decreased serum calcium
Increased serum phosphorus

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Metabolic Bone Diseases

Abnormal mineralization of bone

Deficiency of vitamin D

Rickets

Disease state in growing bone of children & adolescents
Failure of mineralization of bone
Bony deformities

Osteomalacia

Adults
Inadequate or delayed mineralization of bone

Loss of bone mass/ bone tissue

Osteoporosis

Affects women predominantly
Increased risk for fractures, especially hip

A variety of disease states can affect skeletal architecture, strength, and integrity. Some of these disease include rickets, osteomalacia, and osteoporosis.

Rickets and osteomalacia are diseases caused by abnormal mineralization of bone. They result from vitamin D deficiency. Rickets refers to the disease state in growing bone, such as in children or adolescents, while osteomalacia refers to the abnormal mineralization in adult bone. In rickets the patient often demonstrates bony deformities due to the bending of the long bones under the influence of gravity. Both Rickets and osteomalacia are associated with development of secondary hyperparathyroidism. Fractures can result in either case because of poor bone structure.

Osteoporosis is the most common bone disease in adults, occurring mainly in women. Osteoporosis is a disease characterized by low bone mass and deterioration of bone tissue with a consequent increase in bone fragility and bone fracture. Patients with Osteoporosis experience fractures throughout the skeletal system, with the hip and forearm the most common. The most common types of osteoporosis are caused by menopause where the decreased amounts of hormones results in loss of bone mass.

Osteoporosis affects 10.2 million Americans with a 4:1 female to male predominance.

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References

Bishop, M., Fody, E., & Schoeff, l. (2010). Clinical Chemistry: Techniques, principles, Correlations. Baltimore: Wolters Kluwer Lippincott Williams & Wilkins.
Sunheimer, R., & Graves, L. (2010). Clinical Laboratory Chemistry. Upper Saddle River: Pearson .

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