1.3 - Hypocalcemia & Hypercalcemia Flashcards
What is the role of calcium in the body and where is it stored?
- Calcium is essential for bone formation and neuromuscular function.
- Approximately 99% is in bone, 1% in the ECF. Nearly 50% of serum calcium is ionized or free. The remainder is complexed to albumin (40%) and anions such as phosphate (10%).
How are calcium levels regulated in the body?
Calcium balance is regulated by parathyroid hormone (PTH) and calcitriol. PTH increases serum calcium by stimulating bone resorption, increasing calcium reclamation in the kidney and promoting renal conversion of vitamin D to calcitriol. This in turn stimulates the intestinal resorption of calcium.
What is hypocalcemia?
- Occurs when the serum calcium (Ca) concentration is less than 8.6 mg/dl with a normal serum albumin.
- Normal values is 8.6-10.2 mg/dl
What is pseudo hypocalcemia?
- It describes the situation where the total calcium is reduced due to hypoalbuminemia but the corrected calcium remains normal
- Correct serum calcium for decreased albumin
How and why do you get a corrected calcium?
- Calcium in serum is bound to proteins, principally albumin. As a result, the total serum calcium concentration in patients with low or high serum albumin levels may not accurately reflect the physiologically important ionized (or free) calcium concentration.
- Formula for Corrected calcium = serum calcium + 0.8 * (4 - serum albumin)
What are 7 common causes for hypocalcemia?
1. Hypoparathyroidism - usually surgical post thyroidectomy or parathyroidectomy,
- Reduced PTH activity can lead to decreased calcium levels. This can be caused by autoimmune, infiltrative or iatrogenic (surgical) destruction of parathyroid tissue
2. Hypomagnesemia - especially if the magnesium is less than 1.1
3. Pancreatitis - There is a 40-70% incidence in patients with acute pancreatitis due to fat necrosis, release of fatty acids that combine with calcium and form insoluble salts. Known as saponification
4. Vitamin D deficiency
- Malnutrition especially in infants and the elderly
- Fat malabsorption as seen in those with exocrine insufficiency (chronic pancreatitis) or patients with regional enteritis (intestinal fat malabsorption). Also seen in patients with jejunoileal bypass
- Chronic renal failure patients
5. Chronic alcoholism
6. Drugs - including phenytoin, cisplatin and estrogen therapy
7. A low serum free calcium level - common in critically ill patients, possibly due to a cytokine mediated decrease in PTH and calcitriol release with target organ resistance to their effects
What are the subjective findings associated with hypocalcemia?
a. Mental status changes including depression, anxiety and confusion
b. Extrapyramidal changes including tremors, ataxia and dystonia
c. Tetany, circumoral or distal paresthesias
d. Seizures
e. Weakness
What are the physical exam findings associated with hypocalcemia?
a. Chvostek’s sign: facial twitch when tapping on ipsilateral facial nerve
b. Trousseau’s sign: carpal spasm when BP cuff inflated
c. Proximal muscle weakness
d. Dry skin, brittle hair and nails
e. Clues to the diagnosis include a thorough physical examination for evaluation of previous neck surgery, family history of hypocalcemia and review of drugs
What determines the severity of the clinical manifestations of hypocalcemia?
- Clinical manifestations vary with the degree of hypocalcemia and rate of onset.
- The most acute, severe hypocalcemia can cause laryngospasm, confusion, seizures or vascular collapse.
- This would possibly be seen after a parathyroidectomy (total or subtotal). The patients with a higher likelihood would have severe preoperative hypercalcemia removal of a large adenoma, elevated alkaline phosphatase and/or chronic renal disease.
What diagnostic tests can be done to diagnose hypocalcemia?
a. Serum calcium corrected for serum albumin, serum ionized calcium if necessary
b. Serum albumin (normal 3.5 – 4.6 grams/dl). May need to correct serum calcium level
c. Serum magnesium to check for possible hypomagnesemia (seen in about 20% of patients with hypocalcemia
d. PTH level - if it is low or inappropriately normal in the setting of hypocalcemia is indicative of hypoparathyroidism. A high PTH is often found with vitamin D deficiency, PTH resistance and hyperphosphatemia
e. Serum phosphorous – can be helpful in identifying vitamin D deficiency if there is a low calcium and low phosphorous or intravascular chelation of calcium if there is a low calcium and a high phosphorous
f. Vitamin D level
g. EKG – look for a prolonged QTc interval, bradycardia and nonspecific T wave changes
How do you manage a patient with symptomatic hypocalcemia?
If symptomatic with tetany or seizures, has acute hypocalcemia or if NPO:
- Check the phosphorous In severe hyperphosphatemia (> 6.5 mg/dL) administration of calcium may exacerbate the formation of calcifications. In these cases, dialysis may be indicated.
- Check serum magnesium
- Get a corrected calcium
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Treat with one of the following:
- Calcium chloride: 1gram 10% solution IV over 3-5 minutes
- Calcium gluconate: 1 gram 10% solution IV over 3-5 minutes for 2 doses
- Follow with 1 gram/hr calcium gluconate in 500 ml D5W or NS over 3 hours as the effect of the initial infusion is transient.
Calcium gluconate is generally preferred due to a decreased risk of tissue toxicity with possible extravasation.
How do you manage a patient with asymptomatic hypocalcemia?
Treat with:
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Calcium carbonate or another calcium salt. They must receive 2-3 grams elemental calcium a day in divided doses; start with calcium carbonate 500 mg by mouth 3-4 times a day.
- Total daily dose should be 1.5 grams per day.
- Patients will need docusate 250 mg PO BID and or senokot 8.8-17.6 mg by mouth daily along with adequate fluid intake.
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Vitamin D oral preparation
- Choices include ergocalciferol (Drisdol) 50,000-200,000 U orally or IM once a day. Can also use calcitriol (Rocaltrol) 0.5-2 mcg/day
Make sure to monitor for the development of hypercalcemia during calcium supplementation. If it occurs, discontinue both calcium tablets and Vitamin D, Monitor serum calcium until a decline is efficient. Then restart both at a lower dose. If the patient was only treated with calcitriol then the hypercalcemia should resolve in a week.
What is hypercalcemia?
- It is a level of increased total and ionized serum calcium.
- Total serum calcium corrected for serum albumin greater than 10.2 mg/dl or ionized calcium greater than 5.3 mg/dl.
This occurs when the entry of calcium into the circulation exceeds the excretion of calcium into the urine or deposition in the bone.
What are 7 common causes of hypercalcemia?
1. Hyperparathyroidism - 10-20% of these patients have an elevated calcium. This is the most common cause.
- If hypercalcemia has been present for greater than 6 months and no etiology has been discovered, primary hyperparathyroidism is the cause.
- Hypercalcemia in primary hyperparathyroidism is due to PTH mediated activation of osteoclasts leading to increased bone resorption.
2. Malignancy – Most common cause seen in hospitalized patients. It can include solid tumors and leukemia. Tumor types of cancers include lung, renal and breast. This is the second most common cause
- Circulating parathyroid hormone related peptide (protein) (PHRP). The most common cause of hypercalcemia with nonmetastatic solid tumors is secretion of this
- Local bone resorption of metastatic disease
3. Vitamin D excess
- Exogenous intake: high dose Vitamin D plus calcium supplements
- Endogenous production caused by granulomatous diseases such as sarcoidosis
4. Vitamin A intoxication - due to high dose therapy given to patients for tumor treatment
5. Hyperthyroidism, thyrotoxicosis – mild hypercalcemia seen in around 20% of these patients due to a thyroid hormone mediated increase in bone resorption. Correction of the hyperthyroid state typically resolves the increased calcium. If not, a PTH should be evaluated to see if there may be a concomitant etiology
6. Immobilization – patients that are paralyzed or in a total body cast, especially in the young
7. Thiazide diuretic therapy - urinary calcium excretion is decreased. It is not usually a problem in a normal adult but can cause hypercalcemia in a patient with underlying hyperparathyroidism or bone resorption problems
What are the signs and symptoms associated with hypercalcemia?
- Neurological – including lethargy that can progress to coma (possible if calcium > 14 mg/dL), depression, personality changes. The most severe symptoms can also occur in older adults with rapidly rising calcium concentrations.
- Gastrointestinal – N/V, constipation (may be related to decreased smooth muscle tone), and anorexia occur commonly.
- MSK – proximal muscle weakness, bone pain can occur with primary hyperparathyroidism or malignancy
- Renal – polyuria can be caused by the decreased ability to concentrate urine in the distal tubule. Also, nocturia, nephrocalcinosis and ectopic soft tissue calcifications (can occur if the calcium rises above 13 mg/dL). Renal tubular acidosis and renal insufficiency can also be seen.
- Hypertension - can be seen in patients with moderate, chronic hypercalcemia
- Hypotension - can be seen in severe hypercalcemia with volume depletion
The history and physical exam should focus on the duration of the patient’s symptoms, the clinical evidence of any of the usual causes of hypercalcemia and S&S of malignancy. Patients with mild hypercalcemia (< 12 mg/dL) may be asymptomatic or have vague nonspecific symptoms.
What laboratory/diagnostic tests are used to diagnose hypercalcemia?
- Serum calcium corrected for serum albumin, serum ionized calcium if necessary. The first step is to verify with repeat measurement with both to document a true increase
- Parathyroid hormone (PTH) level – an elevated PTH is likely the result of primary hyperparathyroidism; low to normal PTH is most consistent with non PTH mediated hypercalcemia (malignancy, Vitamin D intoxication, chronic granulomatous disorders)
- Thyroid panel including TSH and T3
- Vitamin D levels
- X-rays of bones to assess for changes caused by hyperparathyroidism or metastases
- PHRP level if appropriate
- EKG – look for shortened QTc
