Hypercalcemia (3) Flashcards
What is hypercalcemia defined as?
Serum calcium above the upper limit of normal…
Total calcium > 10.5 mg/dL
Ionized fraction calcium > 5.6 mg/dL
What is considered mild hypercalcemia?
Total calcium 10-12 mg/dL
What is considered moderate hypercalcemia?
Total calcium 12-14 mg/dL
What is considered severe hypercalcemia?
Total calcium > 14 mg/dL
-this is considered a crisis
Total vs ionized calcium
Total calcium is the TOTAL amount of calcium in the blood
It includes free and bound calcium
Normal levels are 8.6-10 mg/dL
And it is an easy/cheap lab to obtain (typically included in BMP)
Ionized calcium is the FREE calcium (calcium unbound to protein - active form)
This is tightly correlated to thyroid function
Normal levels are 4.64 - 5.28 mg/dL (about half of the total calcium)
What labs should be looked at in the initial workup? (6)
- Calcium (total and ionized)
- Albumin (because calcium binds to this protein, so if there is less or more may effect free calcium levels)
- Phosphate (levels are closely associated with calcium levels - inversely related)
- PTH (if high - could be causing the hypercalcemia)
- Vitamin D -
*25-hydroxyvitamin D3 (inactive form)
*1,25-dihydroxyvitamin D3 (calcitriol - active form) - this is increased in non-hodgkin lymphoma - may be causing hypercalcemia - Parathyroid hormone related peptide (PHrP)
-increased in adenocarcinoma or squamous cell cancer - can effect calcium levels
Calcium correction
If we only have the total calcium (not ionized), we need to “correct” it
-it needs to be corrected based on albumin
Corrected calcium (mg/dL) = measured total calcium + 0.8 (4 - serum albumin)
What effect can serum pH have on calcium
the pH effects the binding of calcium to albumin, and therefore effects the ionized/free calcium level
When pH is low (acidosis) = higher ionized calcium (less binding to albumin)
When pH is high (alkalosis) = lower ionized calcium (more binding to albumin)
How does hypercalcemia present?
It is usually asymptomatic
However, if signs/symptoms are present - that means it is SEVERE disease
Pneumonic to remember some symptoms:
Stones, bones, groans, and moans
Stones = renal and pancreatic stones
Bones = bone pain, fractures
Groans = GI pains - constipation, n/v, anorexia/weight loss, peptic ulcer disease
Moans = psychiatric symptoms - malaise, confusion, lethargy
There are also CV symptoms = shortening of QT interval = dysrhythmias
What are the main causes of hypercalcemia (2)
hyperparathyroidism and malignancy (multiple myeloma, neoplasm)
Why is it important to recognize/treat hypercalcemia?
It can lead to coma and death if severe
Calcium absorption
Calcium is primarily absorbed in the small intestine
Only about 10-20% of ingested calcium is absorbed (the rest is used in the skeletal system and other processes of the body that need it)
Normal calcium metabolism (what happens to increase calcium level in the blood?)
Calcium is primarily regulated by PTH and Vitamin D
When calcium levels < 10 mg/dl…
The parathyroid gland stimulated release of parathyroid hormone (PTH)
PTH activates l-alpha-hydroxylase - this is an enzyme that converts calcidiol (inactive vitamin D) into calcitriol (active vitamin D)
Active vitamin D…
-stimulates calcium reabsorption (in the distal part of the nephron)
-stimulates phosphorus excretion
-increases osteoclast production (which increases bone resorption and mobilization of calcium from bone into the blood)
We can target different parts of this pathway (which increases calcium level) to treat hypercalcemia!
Incidence of hypercalcemia in malignancy
Malignancy accounts for 20-30% of hypercalcemia cases
80% die in the first year of treatment
More common in solid tumors than hematologic
-specifically breast, prostate, lung, and multiple myeloma
What are reasons why cancer can cause hypercalcemia (7)
- There are skeletal changes - increased bone resorption causes more release of calcium into serum (increased bone resorption decreased bone formation - unbalances osteoclast/osteoblast activity)
- Decreased renal function is common in cancer - which causes decreased clearance of calcium (increase in serum)
- Immobility - common in cancer patients
- Certain medications
- tumor secretion of PHrP
- Tumor secretion of calcitriol
- osteolytic metastases
What is the most common cancer associated cause of hypercalcemia?
Tumor secretion of parathyroid hormone related protein (PHrP)
In which cancer types can tumor release of PHrP occur? (5)
Lung
Esophagus
Skin
Breast
Kidney
Tumor secretion of parathyroid hormone related protein (humoral hypercalcemia of malignancy) - mechanism of hypercalcemia
The tumor secretes PHrP - this is structurally very similar to PTH
It increases bone resorption (increasing calcium release into blood)
Causes distal tubule calcium reabsorption
Inhibits phosphate transport
And it decreases levels of PTH and active Vitamin D