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Back to the basics: calcium and phosphorus 101.


Disorders of calcium metabolism are usually associated with alterations of phosphorus (as inorganic phosphate). Therefore, the metabolism of these two substances will be considered together.

Calcium and phosphorus enter the body via the gastrointestinal tract and are absorbed by the small intestine with the aid of vitamin D and parathyroid hormone (PTH). Absorption is enhanced by the acid pH of the intestine.

Calcium is involved in a variety of roles in human physiology. In bone, calcium combines with phosphorus to form hydroxyapatite crystals that give strength to bone structure and provide a reservoir of calcium for the remainder of the body. Ninety-nine percent of the calcium and 80% of the phosphorus in the body are associated with the skeletal system. Therefore, from a quantitative point of view, the most important function of calcium and phosphorus is in the maintenance of skeletal structure. Calcium also functions in blood coagulation (factor IV), muscle contraction, enzyme activation, and membrane permeability. Phosphorus is a necessary component of nucleic acids, phospholipids, adenosine triphosphate (ATP), and a number of carbohydrate intermediates. Calcium and phosphorus utilized in these processes are in constant equilibrium with their circulating concentrations.

Reference Ranges

Reference ranges for serum calcium are dependent up the laboratory methodology and instrument utilized and should be interpreted in the context of that individual laboratory's reported reference range. In general, the reference range for calcium is approximately 8.5-10.5 mg/ dL in adults and 10.5-12.5 mg/dL in growing children. The reference range for phosphorus in adults is between 2.5-4.5 mg/dL and 4.5-6.5 mg/dL in growing children. Healthy adults with average diets excrete phosphorus at the rate of 900-1300 mg/24 hours and calcium at a rate of 30-150 mg/24 hours.

Forms of Calcium

Calcium is found in the blood in three forms: (1) ionized (50%), (2) protein-bound (45%), and (3) complexed (5%). The protein-bound fraction is bound predominately to albumin while the remainder is bound to globulins. The complexed form is loosely bond to citrate, phosphate, and sulfate. The ionized form is biologically active and has been termed diffusible calcium. In cases of acidosis the ionized form increases while in alkalosis the ionized form decreases. Plasma protein concentration and pH help to determine the amount of ionized calcium in the blood.

Regulation of Calcium

Several factors are involved in the regulation of serum calcium and as a general rule, these factors also affect serum phosphorus. There are three hormones that can be considered controlling hormones since the concentration of these hormones is altered in response to serum calcium levels. The first hormone is parathyroid hormone (parathormone, PTH), which is stimulated by a decrease in calcium, and conversely an increase in calcium will turn off the secretion of PTH. PTH exerts its effect on both the kidneys and bone. In the kidneys PTH increases tubular reabsorption of calcium and decreases reabsorption of phosphorus. PTH also stimulates renal production of 1, 25-dihydroxycholecalciferol which causes an increase in intestinal absorption of calcium and phosphorus. In bone, PTH acts on osteoclasts of the bone causing bone resorption and subsequent release of calcium to the extracellular fluid.

The second hormone is calcitonin (CT) which originates from the C cells or parafollicular cells of the thyroid and thymus glands. CT is secreted in response to high calcium levels and acts to lower serum calcium levels. CT also inhibits bone resorption by increasing the number of osteoblasts, causing a shift toward bone formation and calcium utilization. CT also increases excretion of calcium, sodium, and phosphorus through the kidneys.

The third hormone is vitamin D or cholecalciferol (CC or Vitamin D3). The precursor of vitamin D3 is 7-dehydrocholesterol also known as provitamin D3. Following exposure to UV-B radiation, the provitamin is converted to vitamin D3 which is biologically inactive. Vitamin D3 is most often obtained either nutritionally (diet or supplement) and via exposure of the skin to sunlight. This process is inhibited by application of sunscreens of SPF 8 or greater. Vitamin D3 in this form must be further metabolized before it can exert an effect on calcium levels. Vitamin D3 which originates in the intestine or epidermis is transported to the liver where it is converted to 25-hyroxycholecalciferol and then to the kidney where it is further metabolized by hydroxylation to 1, 25-dihydroxycholecalciferol which is biologically active. 1, 25-dihyroxycholecalciferol then exerts its effects on the (1) intestine to increase calcium absorption, (2) bone to increase resorption, and (3) kidneys to increase reabsorption by the proximal tubules.

Three other groups of hormones also exert an influence on serum calcium level: (1) thyroid hormones, (2) adrenal steroid hormones, and (3) sex hormones. Thyroid hormones (thyroxine and triiodothyronine {T4 and T3}) cause increased mobilization of calcium in bone. The adrenal steroid hormones (glucocorticoids) may alter excretion of calcium by the kidneys, particularly in cases of renal insufficiency and induce osteoporosis. Finally, the sex hormones (estrogen, progesterone, and testosterone) have been related to calcium levels and loss of bone mass in postmenopausal women leading to osteoporosis.

Clinical Significance of Calcium

Hypocalcemia (low calcium in the blood) can be observed in cases of osteomalacia, hypomagnesemia, vitamin D deficiency, hypoparathyroidism, steatorrhea, pregnancy and lactation, nephrosis, nephritis, and hepatocellular or renal parenchymal cell disease. The major symptom associated with hypocalcemia is increased neuromuscular excitability which can lead to tetany and convulsions. With prolonged hypocalcemia, cataracts and psychiatric symptoms such as depression may occur.

Hypercalcemia (elevated calcium in the blood) is also noted in a variety of conditions such as hyperparathyroidism, hypervitaminosis D, bone neoplasms, milk-alkali syndrome (seen in patients who ingest large amounts of milk or alkali for relief of gastric acidity associated with peptic ulcer disease), sarcoidosis, thyrotoxicosis, multiple myeloma, and polycythemia rubra vera. Symptoms of hypercalcemia may include nausea, vomiting, abdominal pain, polyuria, calcium phosphate calculi formation in the bladder and ureters, and abnormal calcification of other tissues.

Calcium and phosphorus levels tend to maintain an equilibrium in the blood and changes in calcium level are often reflected reciprocally in the phosphorus level. Therefore, low serum calcium levels are often accompanied by increased serum phosphorus levels. The converse also holds true.

Clinical Significance of Phosphorus

Hypophosphatemia (low phosphorus in the blood) may be observed in hyperparathyroidism, Fanconni anemia (a genetic defect affecting the proximal tubules), vitamin D deficiency causing rickets in children and osteomalacia in adults, chronic use of antacids which bind phosphates in the intestine, chronic alcoholism, malabsorption syndrome, and sometimes associated with administration of hyperalimentation fluids.

The symptoms of hypophosphatemia include muscle weakness and pain, rhabdomyolysis (muscle necrosis), metabolic acidosis, central nervous system (CNS) changes such as confusion and a dulled sensitivity to pain, leukocyte dysfunction, and signs of cardiac failure due to cardiomyopathy.

Hyperphosphatemia is caused by chronic renal failure, Addison's disease, hypervitaminosis D, cytotoxic treatment of certain leukemias, lymphomas, metastatic bone tumors, diabetic ketoacidosis, and healing bone fractures.

Large quantities of phosphorus (as inorganic phosphate) are excreted by the kidneys; thus when the kidneys are not functioning properly retention of phosphorus results. Since urea nitrogen (BUN) and creatinine levels are an indication of kidney function, one might expect that an elevated BUN and/or creatinine might be accompanied by and elevated phosphorus level.

The concentration of phosphorus in circulation is influenced by parathyroid gland function, intestinal absorption, renal function, bone metabolism, and nutrition. Thus a request for a phosphorus determination is appropriate when investigating the possibility of these diseases in a particular patient.

Samples for Testing

Ideally, patients should be fasting since serum values for phosphorus are generally lower following a meal. Either heparinized plasma or serum is suitable for analysis of calcium and phosphorus. Other anticoagulated plasma samples are unacceptable due to chelation of calcium. Grossly lipemic samples may cause falsely elevated results while hemolyzed samples exhibit a negative bias due to interference with color formation in some methods.

Suggested Readings

Endocrine Control of Calcium and Phosphate Homeostasis downloaded 1/11/2015 from hbooks/pathphys/endocrine/thyroid/calcium.html

Calcium Homeostasis downloaded 1/11/2015 from http://courses/

Disorders involving Calcium, Phosphorus, and Magnesium downloaded 1/11/2015 from

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1. The protein-bound component of total calcium is the biologically active component of serum calcium.

A. True

B. False

2. Phosphorus is most closely associated with which of the following?

A. Muscle contraction

B. Coagulation mechanisms

C. Membrane permeability

D. Component of nucleic acids

3. A decreased level of which of the following hormones is associated with loss of bone mass and development of osteoporosis in females?

A. Estrogen

B. Parathormone

C. Thyrocalcitonin

D. Triidothyronine

4. Which of the following hormones related to calcium levels in the body acts by increasing osteoblastic activities and decreasing serum calcium levels in the body?

A. T4

B. Estrogen

C. Parathormone

D. Thyrocalcitonin

5. Which of the following is MOST commonly associated increased BUN and creatinine levels of chronic renal disease?

A. Hypocalcemia

B. Hypercalcemia

C. Hypophosphatemia

D. Hyperphosphatemia

6. Based upon the normal values provided by the author, a serum calcium of 12.0 mg/dL would be considered a normal finding in:

A. A 12-year-old child

B. A 22-year-old diabetic in ketoacidosis

C. A 46-year-old male with end-stage renal disease

D. A 65-year-old female with a broken hip due to osteoporosis

7. A serum calcium of zero (0) was noted on a sample submitted from the Emergency Room for a Comprehensive Metabolic Profile (CMP). What is the MOST likely cause of this finding?

A. The patient may have multiple myeloma.

B. An incorrect sample was submitted for testing.

C. Patient was not fasting and sample was lipemic.

D. The sample is from a patient with severe osteoporosis.

8. Which of the following hormones necessary for normal calcium metabolism is produced in the body following exposure of the skin to sunlight?

A. Thyroxine

B. Calcitonin

C. Cholecalciferol

D. Parathyroid hormone

9. A common finding in patients with hyperparathyroidism would be:

A. Hypocalcemia and hypophosphatemia

B. Hypocalcemia and hyperphosphatemia

C. Hypercalcemia and hypophosphatemia

D. Hypercalcemia and hyperphosphatemia

10. Which of the following findings would support a diagnosis of tetany?

A. Hypocalcemia

B. Hypercalcemia

C. Hypophosphatemia

D. Hyperphosphatemia

George Roberts, Ed.D., MT(AMT), MLS(ASCP), Dean, School of Health Sciences, Natural Sciences and Math, Louisiana Delta Community College, Monroe, LA
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Author:Roberts, George H.
Publication:Journal of Continuing Education Topics & Issues
Article Type:Report
Geographic Code:1USA
Date:Jan 1, 2015
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