Calcium Total

Sample for Calcium Total

1. It is done on the serum of the patient.
2. The blood should be collected without much pressure on the arm.
   1. Avoid prolonged tourniquet.
3. EDTA cannot be used as an anticoagulant for the plasma.
4. Obtain blood with minimal venous occlusion and without exercise or after restoring circulation.
5. The serum is stable for 8 hours at 22 to 25 °C. But can keep at 4 °C for a longer period.

Purpose (Indications) of Calcium Total

1. The serum level of calcium is used to evaluate parathyroid function and metabolism.
2. Serum calcium level is used to monitor renal failure and renal transplantation.
3. Serum calcium level is used to evaluate hyperparathyroidism.
4. Serum calcium levels may be done in malignancies like multiple myeloma.
5. Serum calcium levels may be done to monitor calcium levels before and after blood transfusions.
6. It is advised following thyroidectomy and parathyroidectomy.
7. It is advised in acute pancreatitis.
8. It is advised in various drugs to see their effect.

Precautions for Calcium Total

1. Venous stasis during blood collection by prolonged tourniquet application increases the calcium level.
2. A fasting specimen is preferred.
3. Venous stasis or erect posture increased the calcium level by 0.6 mg/dL.
4. Diurnal variation is higher in PM (around 9 PM) than in AM (lowest).
5. Separate serum immediately from RBCs to avoid calcium uptake by these cells (RBCs).
6. Excessive intake of milk leads to increased calcium levels.
7. Vitamin D intoxication also increases the calcium level.
8. Check the albumin level because hypoalbuminemia leads to an artificial decrease in the calcium level.
9. Drugs like calcium salts, alkaline antacids, thiazide diuretics, vitamin D, parathyroid and thyroid hormones, and androgens may increase the serum calcium level.
10. Drugs like aspirin, anticonvulsants, heparin, laxatives, diuretics, magnesium salts, and oral contraceptives may decrease the calcium level.
11. Calcium is increased by hyperalbuminemia, like in multiple myeloma and Waldenstrom macroglobulinemia.
12. It is increased by dehydration.
13. Hyponatremia (<120 meq/L) increases the protein-bound fraction of calcium. At the same time, hypernatremia decreases serum calcium.
14. The hemodilution decreases serum calcium.

Definition of Calcium (Total):

1. Calcium (Ca ⁺⁺) is our body’s 5th most common element and most common cation in our body.
2. The average human body contains around 1 kg (24.95 mol) of calcium.
3. Calcium is found in the skeleton, soft tissue, and extracellular fluid.
4. A calcium daily intake of calcium is about 400 mg is needed by the body.
5. The minerals required by our body are:
   1. Sodium.
   2. Potassium.
   3. Calcium.
   4. Chloride.
   5. Phosphorus.
   6. Magnesium.
   7. Organically bound-S.
6. Other elements required in trace amounts are:
   1. Iron.
   2. Zinc.
   3. Copper.
   4. Manganese.
   5. Selenium.
   6. Chromium.
   7. Molybdenum.
   8. Cobalt.
   9. Iodine.

Calcium Metabolism:

Calcium distribution:

1. There is a large amount of calcium in the body, mainly in the bones and teeth.
2. About 99% of calcium is deposited in the skeleton as a mixture of:
   1. Amorphous calcium phosphate.
   2. Crystalline hydroxyapatite.
   3. Calcium phosphate crystal (hydrated).
3. A small amount of fluoride is incorporated into the calcium phosphate in the teeth and bone.
4. Half of the calcium in blood circulation is free in ionized form, and half is protein-bound, mostly with albumin.
   1. 50% free or ionized (active) form of calcium.
   2. 40% is bound to the protein of calcium.
      1. 80% of calcium is bound to albumin, and 20% is bound to globulin.
   3. 10% is complex with anions.
      1. Some physician prefers ionized serum calcium level to avoid the effect of albumin level.

5. Complexed calcium is complexed with small diffusible anions:
   1. Bicarbonate.
   2. Lactate.
   3. Phosphate.
   4. Citrate.
6. Calcium in the blood is virtually all present in the plasma.
7. It increases in acidosis and decreases in alkalosis.
8. An increase in the plasma proteins leads to an increase in serum total calcium.
9. Decreased plasma proteins lead to a decrease in the total serum calcium.
10. Half of the calcium in blood circulation is free in ionized form, and half is protein-bound, mostly with albumin.

Distribution of calcium in the body:

Intake of calcium and balance (Absorption and excretion):

1. Most individuals ingest 500 to 1000 mg of calcium daily in their food.
   1. They excrete excess amounts in the feces and urine.
   2. Dairy products like milk and cheese are good sources of calcium.
   3. A large amount of dietary calcium is not absorbed because of the formation of insoluble calcium compounds like PO₄, oxalate, phytate, and soap in the intestine and excreted in the feces.
2. Calcium balance is maintained by:
   1. Absorption of calcium from the intestine.
   2. Excretion by the kidneys.
   3. Movement of calcium in and out of the bones.

3. Calcium phosphate in the bone is not an inert substance.
4. There is dynamic equilibrium with Ca⁺⁺ and HPO4^– of the body fluids by resorption and deposition.

Distribution of the calcium in the body

 Calcium functions:

1. Calcium is also needed to maintain metabolic processes like muscle contraction, the transmission of neural impulses, clotting of the blood, cardiac function, and inhibit cell destruction.
2. Calcium stabilizes the plasma membranes and influences permeability and excitability.
3. The intracellular calcium functions are:
   1. Muscle contraction.
   2. Hormone secretion.
   3. Glycogen metabolism.
   4. Cell division.
   5. Activation of enzymes.
   6. Transfer of the ions across the cell membrane.
4. The intracellular calcium is bound to:
   1. Protein in the cell membrane.
   2. Present in the mitochondria.
   3. Present in the nucleus.

5. The extracellular calcium (extracellular calcium provides calcium ions) functions are:
   1. Bone Mineralization.
   2. Blood coagulation factors.

1. 3. Plasma membrane potential.
   4. Maintenance of intracellular calcium.
   5. Calcium decreases neuromuscular excitability.

Calcium control mechanism:

1.  Hypocalcemia:
   1. Normally the level of calcium in the blood is carefully controlled. When blood calcium levels get low is called hypocalcemia.
   2. The bones release calcium to bring them back to a normal blood level.
2. Hypercalcemia:
   1. When blood calcium levels get high is called Hypercalcemia.
   2. The extra calcium is stored in the bones or passed out of the body in stool and urine.
3. Body serum calcium levels are maintained:
   1. By a parathyroid Hormone PTH (Parathyroid gland hormone, calcium regulating hormone).
   2. Calcitonin (produced by C or parafollicular thyroid cells) also plays a role in the control of serum calcium.

4. The ectopic PTH-like hormone may be secreted by the tumors of the lung, breasts, and kidneys.
5. PTH increases the serum calcium level:
   1. By increasing bone resorption.
   2. By mobilizing Calcium.
   3. PTH indirectly increases calcium absorption from the gastrointestinal tract by producing vit. D.

6. PTH also increases the excretion of phosphate in the urine.
   1. Calcitonin decreases serum calcium and phosphate levels by inhibiting bone resorption.
   2. Decreasing calcium levels increases PTH, activating the calcium reservoir and releasing it into circulation.
7. Calcium binds to negative charge sites on the proteins, depending on the pH.
8. Alkalosis, increased negative charge sites on proteins lead to increased calcium binding and decreased free calcium levels.

Calcium in alkalosis

9. In acidosis, negative charge sites are decreased, leading to increased free calcium.
10. A patient with low serum albumin will have low serum calcium.
11. So the serum albumin level may be estimated with the serum calcium level. Serum calcium level decreases to 0.8 mg with every decrease of 1 gram of albumin.

Effect of the albumin on serum calcium:

1. A decrease in 1 gram/dL of serum albumin decreases total serum calcium by around 0.8 mg/dL.
2. This is the average decrease, but this may change in different situations.
3. Because no effect of serum albumin on ionized calcium is preferred.

Hypocalcemia:

Etiology of hypocalcemia:

1. The most common cause is hypoalbuminemia.
   1. One gram/dL of albumin binds 0.8 mg/dL of calcium.
      1. So there may be decreased albumin-bound calcium.
      2. Or decrease in free calcium.
2. Chronic renal failure leads to hypocalcemia because:
   1. There is an increased loss of protein by the kidney in the urine.
   2. There is hyperphosphatemia.
   3. There is decreased serum 1,25(OH)₂ D.
   4. There is skeletal resistance to PTH.

Signs and symptoms of hypocalcemia:

1. Neuromuscular hyperexcitability.
   1. Like tetany.
   2. Paresthesia.
   3. Seizures.
2. A rapid fall in calcium level may lead to hypotension.
3. Acute symptomatic hypocalcemia may be associated with the following:
   1. Rapid remineralization of the bone after the surgery of primary hyperparathyroidism is called hungry bone syndrome.
   2. Acute pancreatitis.

Hypercalcemia:

Etiology of hypercalcemia:

1. Hypercalcemia is due to an increase in the increased influx of calcium into the extracellular compartment from the:
   1. Skeletal system.
   2. Intestine.
   3. Kidney.
2. Primary hyperparathyroidism is the most common cause in outdoor patients.
3. Malignancy is the most common cause of hospitalized patients.
   1. The above two conditions constitute 90% to 95% of the causes of hypercalcemia.
4. Also seen in 10% to 20% of the cases of cancers.
5. Hypercalcemia (malignancy-associated)  is seen in the following cancers:
   1. Myeloma = 30% (20% to 50%).
   2. Renal cell carcinoma = 11% (10% to 13%) due to ectopic production of PTH.
   3. Lung cancers = 10% (7% to 13%) due to ectopic production of PTH.
   4. Breast = 15% 7% to 23%) due to ectopic production of PTH.
   5. Non-Hodgkins lymphoma = 5% (3% to 13%).
   6. Leukemia = 3% (2% to 11%).
6. Some lymphomas may produce 1,25(OH)₂ D  and cause hypercalcemia.
7. Primary sarcoidosis shows hypercalcemia in 5% to 10% of the cases (1% to 62%).

Symptoms of hypercalcemia are:

1. Anorexia.
2. Lethargy.
3. Nausea.
4. Vomiting.
5. Ultimately coma.
6. Other patients may show:
   1.  Nervousness.
   2. Excitability.
   3. Tetany.

To label hypercalcemia, one should have the following:

1. Three separate raised levels of calcium.
   1. Serum or plasma calcium = >10.3 mg/dL
   2. Ionized calcium = >1.30 mmol/L.

A normal  Calcium total:

Source 1

• Infant to one month = 7.0 to 11.5 mg/dL.
• One month to one year = 8.6 to 10.2 mg/ dL.
• Adult = 9 to 10.5 mg/dL.
  • Its low level may lead to tetany.

Source 2

• The conversion factor is x 0.25 for SI unit mmol/L

Hypercalcemia (plasma level = >10.5 mg/dL) may be seen in the following conditions :

1. Hyperparathyroidism (primary and secondary).
2. Hyperthyroidism.
3. Acute and chronic renal failure.
4. Following renal transplant.
5. Metastatic bone tumor of lung, breast, and kidney.
   1. Bone metastasis is around 30% of the cases.
6. 2% of Hodgkin’s lymphoma and non-Hodgkins lymphoma.
7. Milk-alkali syndrome.
8. Multiple myelomas.
9. Paget’s disease.
10. Osteomalacia with malabsorption.
11. Aluminum-associated osteomalacia.
12. Granulomatous diseases:
    1. Sarcoidosis (mostly uncommon).
    2. Tuberculosis.
    3. Leprosy.
13. Uncommonly may be seen in:
    1. Mycosis.
    2. Berylliosis.
    3. Silicon granuloma.
    4. Crohn’s disease.
    5. Eosinophilic granuloma.
14. Tumors produce a PTH-like substance.
15. Vitamin D intoxication.
    1. Ectopic production of 1,25 -dihydroxy -vitamin-D3, e.g., from Hodgkin’s and Non-Hodgkin’s lymphoma.
16. Vitamin A intoxication.
17. Excessive calcium intake.
18. Prolonged immobilization.
19. Thiazide diuretics.
20. Withdrawal of steroids.
21. Most (80 to 90 %) of hypercalcemia cases are due to hyperparathyroidism or malignancy.
22. Thyrotoxicosis in 20% to 40% of the cases is usually <14 mg/dL.
23. Multiple endocrine neoplasias.
24. Hypercalcemia is also seen in some of the neoplasms:
    1. Breast =  15% (7 to 23%).
    2. Lung = 10% (7 to 13%).
    3. Kidneys =  11% (10.5 to 13%).
    4. Colon = 5%.
    5. Cervix = 7%
    6. Non-Hodgkin’s lymphoma = 5% (3 to 13%).
    7. Leukemia = 3% (2 to 11.5%)
    8. Multiple myeloma = 30% (20 to 50%).

Causes of Hypercalcemia (>10.5 mg/dL):

Hypocalcemia (plasma level = <8.5 mg/dL) may be seen in the following conditions :

1. Hypoparathyroidism.
   1. Surgical.
   2. Idiopathic.
   3. Infiltration of the parathyroid gland by sarcoidosis, amyloidosis, hemochromatosis, and neoplasm.
   4. Hereditary conditions like DiGeorge syndrome.
2. Pseudohypoparathyroidism is due to a lack of response to PTH.
3. Malabsorption (inadequate absorption of nutrients from the intestinal tract).
4. Hypoalbuminemia.
5. Osteomalacia
6. Pancreatitis
7. Renal failure (chronic). Chronic renal failure with uremia and phosphate retention.
   1. It is also seen in Fanconi syndrome and renal tubular acidosis.
8. Bone diseases like osteomalacia and rickets.
9. Malabsortion of calcium and vitamin D.
   1. Insufficient ingestion of calcium, phosphorus,  and vitamin D.
   2. Starvation.
10. Liver disease (decreased albumin production).
    1. Obstructive jaundice.
11. Hypomagnesemia.
12. Hyperphosphatemia like phosphate enema and infusion.
13. Drugs like:
    1. Cancer chemotherapy like cisplatin, cytosine arabinoside, and mithramycin.
    2. Antibiotics like ketoconazole, gentamicin, and pentamidine.
    3. Chronic use of anticonvulsant drugs like phenobarbitol and phenytoin.
    4. Use of calcitonin.
    5. Excessive use of fluoride (fluoride intoxication).
14. Neonates of complicated pregnancies.
    1. Infants of diabetic mothers.
    2. Premature babies.
15. In the case of osteoblastic tumor metastasis.
16. In the case of cerebral injuries.
17. Temporary hypocalcemia after subtotal thyroidectomy was seen in >40% of the patients, and >20% showed signs and symptoms.

Lab findings of hypocalcemia:

Causes of hypocalcemia and lab findings:

The most common cause of hypocalcemia:

It may be seen in Hypoalbuminemia, in which the ionized fraction may be normal while the total calcium level is decreased due to the low percentage of calcium bound to albumin.

• A correction formula is needed as follows:
  • Corrected calcium level = measured calcium — albumin g/dL + 4

 Natural foods are a good source of calcium:

Critical values:

• Acute hypo or hypercalcemia can be life-threatening
• > 14 mg/dL Hypercalcemia leads to come and cardiac arrest.
• < 4 mg/dL Hypocalcemia leads to tetany (another reference says <6.5 mg/dL).

Questions and answers: