Pharmacology of Parathyroids and Bone Flashcards
What type of bone is in the shafts of long bones? vertebral bodies, ribs, pelvis and ends of long bones?
- shafts-cortical
- vertebral bodies, ribs, pelvis and ends of long bones-trabecular
What are the 3 main cell types in bone and what is their function?
- osteoblasts-bone forming cells
- osteoclasts-bon resorption
- osteocytes-communication and mobilization
What are the 2 types of matrix in bone and what are they made up of?
organic-type 1 collagen and proteins
inorganic-hydroxyapatite
What controls the secretion of PTH?
-ionized calcium (when low PTH is stimulated)
Which 2 organs does PTH directly effect?
- bone-releases Ca from bone (activates osteoblasts which activate osteoclasts–>according to pathoma)
- Kidney-reabsorbtion of Ca and production of Vitamin D which leads to absorbtion of Ca and PO4 in small intestine
- All lead to increased serum Ca levels*
What are the 3 forms of Ca in the circulation and which are the most important physiologically?
1) Ionized Ca
2) protein bound Ca
3) Complexed to bicarb, citrate or phos
* *Ionized and free more important physiologically**
Changes in which protein in the blood can affect the measurement of calcium?
albumin
What is the equation to correct Ca based on albumin levels?
corrected Ca= measured Ca+.8 X (4-measured albumin)
What 3 things can increase PT reabsorbtion of Phosphorous?
- phosphate depletion
- hypoparathyroidism
- hypocalcemia
What increased Phosphate excretion?
- PTH
- PTHrp
- hypercalcemia
- hypokalemia
- hypomagnesemia
- calcitonin
- glucocorticoids
- diuretics
What is magnesium necessary for?
the release of PTH and the action of PTH on its target tissues
Where is Vitamin D made? Where do it’s 2 hydroxylations occur? How does it maintain normal serum Ca level?
- made in the skin
- hydroxylations in the liver and kidney
- mantains Ca by increasing absorption of dietary Ca and stimulating bone cells to become osteoclasts
If a patient has hypercalcemia and their PTH level is not suppressed (high or normal) what do they most likely have?
primary hyperparathyroidism-excessive secretion of PTH from parathyroid glands (usually in 6th decade of life)
If a patient has hypercalcemia and their PTH level is low, what other tests should be ordered in order to make a dx?
-PTHrp, Vitamin D, and 24 hour urine calcium
What would the lab values of Ca, PTH, Phosphorous and Urine calcium be like in primary hyperparathyroidism?
- Ca high
- PTH high or normal
- Phosphorous low
- Urine calcium high
What are some of symptoms of primary hyperparathyroidism?
lethargy drowsiness stupor coma proximal muscle weakness hyporeflexia N/V pancreatitis Polyuria Polydipsia Nephrocalcinosis Nephrolithiasis HTN Short QT bradycardia increased sensitivity to digitalis
How is primary hyperparathyroidism usually treated?
Surgery to remove abnormal tissue
if disease is mild or asymptomatic they could be followed
What medications can be used to medically treat hyperparathyroidism?
- Bisphosphonates-tx low bone density
- Calcimimetics: to reduce PTH and Ca levels by altering fxn of Ca sensing receptor
- Sensipar (Cinacalcet): for hyperparathyroidism in renal disease and parathyroid carcinoma or in pts who refuse surgery
What are some other causes of hypercalcemia aside from hyperparathyroidism?
- malignancy
- Familial hypocalciuric hypercalcemia-PTH is normal or slightly high
- milk alkali syndrome-excessive OTC Ca use
- Granulomatous Diseases-can increase Vit D levels
- Medications: thiazides and Lithium
What are the 3 general ways to decrease serum Ca?
- expand volume
- increase urine Ca excretion
- inhibit bone resorption
How is mild hypercalcemia treated? (Ca<12)
increase fluid intake
moderate Ca in diet
avoid certain meds
What are the 5 main treatments for hypercalcemia?
- fluids-possible need for loop diuretic after to increase Ca excretion and prevent volume overload
- Bisphosphonates
- calcitonin
- corticosteroids
- Dialysis
What is the mechanism of Biphosphonates and what are the 2 most commonly used?
- inhibits bone resorption
- Pamidronate and Zoledronic Acid
- Not effective immediately*
What is mechanism of calcitonin and what can repeated exposure lead to, making it most useful in the acute setting?
- rapid lowering of Ca by increasing urinary Ca excretion and inhibiting bone resorption
- repeated exposure can lead to downreg of calcitonin receptors–>tachyphylaxis in 2-3 days
- *lowers Ca 1-2mg/dl within 2-4 hours–>Thus used for SEVERE Hypercalcemia**
What is the mechanism of corticosteroids in the treatment of hypercalcemia?
- decreases production of Vitamin D
* *Used in Vit D intoxication, granulomatous diseases and hematologic malignancies**
