Hyper/Hypocalcemia

Question 1

which form of serum calcium is active?

Answer 1

ionized calcium - biologically active, ~50% of serum Ca2+

the rest is bound to albumins, globulins, or anions (citrate, phosphate)

important to measure because ionized Ca2+ can be normal in presence of abnormal total serum Ca2+ or vice versa

Question 2

how can albumin affect serum calcium levels?

Answer 2

much of blood Ca2+ is bound by albumin, but the active form of Ca2+ is ionized

low/high albumin can cause “pseudo-hypo/hypercalcemia” - ionized calcium is normal but there is low total serum calcium

Question 3

how will the following affect blood calcium labs?
a. dehydration
b. nephrotic syndrome
c. cirrhosis

Answer 3

much of blood Ca2+ is bound by albumin, but the active form of Ca2+ is ionized

a. dehydration (high albumin) —> pseudo-hypercalcemia

b. nephrotic syndrome and c. cirrhosis (low albumin) —> pseudo-hypocalcemia

Question 4

how can plasma pH alter calcium labs?

Answer 4

active calcium is in ionized form

acidemia (low pH) increases ionized calcium (and alkalemia lowers it)

so total serum calcium can be normal, but the active form (ionized) is not

Question 5

how does hypercalcemia cause skeletal muscle weakness?

Answer 5

Ca2+ inhibits Na+ movement through voltage-gated channels —> decreased excitability

Question 6

what is the effect of hypercalcemia on renal function?

Answer 6

decreases ability to concentrate urine (NKCC down-regulation, decreased aquaporin expression) —> polyuria, significant volume depletion

can also cause nephrolithiasis (calcium kidney stones)

Question 7

what is the mechanism by which hypercalcemia shortens the QT interval?

Answer 7

L-type Ca2+ channels (plateau, phase 2) depend on intracellular Ca2+ to close

increased Ca2+ influx causes L-type channels to close earlier

Question 8

what is the most common cause of primary hyperparathyroidism?

Answer 8

sporadic parathyroid adenoma: encapsulated lesions composed of neoplastic chief cells (monoclonal), 1 gland involved

Question 9

how is primary hyperparathyroidism diagnosed? (2)

Answer 9

1. lab: high calcium + low phosphate + high PTH
2. imaging: ultrasound or sestamibi scan (nuclear medicine which is performed to localize parathyroid adenoma)

Question 10

if a patient with hypercalcemia is found to have parathyroid hyperplasia (multiple glands involved), what disease should you consider?

Answer 10

consider multiple endocrine neoplasia (MEN) type 1 or 2A

type 1: parathyroid hyperplasia, pituitary tumor, pancreatic islet cell tumor (insulinoma) - esp. this type, primary hyperparathyroidism is commonly #1 presentation

type 2A: parathyroid hyperplasia, pheochromocytoma, medullary carcinoma of thyroid

Question 11

when evaluating a patient with hypercalcemia, what are the first 3 steps?

Answer 11

1. restore intravascular volume! Hypercalcemia can result in significant volume depletion
2. confirm elevated ionized (active) Ca2+
3. check PTH levels (is it PTH dependent or independent?)

Question 12

what are the 3 major causes of hypercalcemia with low or undetectable PTH?

Answer 12

1. malignancy (via PTHrP secretion by squamous cell cancer, renal cell carcinoma, non-Hodgkin lymphoma, multiple myeloma)
2. medication (vitamin D, thiazides, milk-alkali)
3. extra-renal vitamin D synthesis (granulomatous disease, lymphoma)

Question 13

what is the triad of milk-alkali syndrome?

Answer 13

caused by ingestion of large amounts of calcium and absorbable alkali

1. hypercalcemia with hypercalciuria —> diuresis
2. metabolic alkalosis
3. acute kidney injury

Question 14

what is the most common cause of hypoparathyroidism in adults?

Answer 14

surgery - thyroidectomy, radial neck dissection (for squamous cell carcinoma of oropharynx), etc

Question 15

what kind of drug is cinacalcet?

Answer 15

cinacalcet: calcimimetic used to treat end-stage renal disease —> reduces PTH secretion to treat bone demineralization caused by high PTH

binds to calcium-sensing receptors