Unit 5 - Parathyroids and Bone

Question 1

relationship between OPG/RANKL/RANK

Answer 1

RANKL = ligand that is related to TNF
RANK and OPG (osteoprotegerin) are key regulators of resorption, and receptors for RANKL and TNF
-OPG inhibits bone resorption (physiological and pathological)

Question 2

what are bone turnover markers?

Answer 2

formation: bone-specific alkaline phosphatase and osteocalcin
resorption: serum TRAP, serum/urine NTx and CTx

Question 3

control and actions of PTH

Answer 3

• when Ca++ level falls, PTH is stimulated (inverse relationship)
• mainfunction is to defend VS hypocalcemia (activates AC –> increase cAMP release)
• -stimulate bone resorption by OC (indirectly thru OBs)
• -stimulate renal tubular absorption of Ca and Mg
• -inhibit renal tubular reabsorption of PO4 and bicarb
• -stimulate synthesis of active vit D (calcitriol) from 25 form in kidney

Question 4

how does Ca circulate in the plasma?

Answer 4

1. ionized (50%); active
2. protein-bound (40%); mostly to albumin
3. complexed to bicarb, citrate, PO4

Question 5

what does acidosis and alkalosis do to Ca binding to albumin?

Answer 5

acidosis: decreases binding (increases active ionized Ca), enhances tubular reabsorption
alkalosis: increases binding (decreases active ionized Ca), increases tubular clearance

Question 6

what is the main determinant of intestinal absorption of Ca and P?

Answer 6

1,25-(OH)2D

Question 7

who can get phosphorus deficiencies?

Answer 7

alcoholics and people taking antacids with Al (binds phosphate to prevent absorption; used to prevent hyperophosphatemia in renal failure)

Question 8

how is Mg related to PTH?

Answer 8

it is necessary for its release, and for action of hormone on its target tissues
-if Mg low, PTH is stimulated and vice versa

Question 9

what do furosemide and cisplatin do to Mg reabsorption?

Answer 9

inhibit reabsorption in LoH

Question 10

what is “transient hypocalcemia” seen in?

Answer 10

postoperatively after hyperparathyroid treatment

• normal, but suppressed parathyroid glands are regaining sensitivity to Ca++, and usually mild
• if prolonged, it’s rare and rapid deposition of Ca and PO4 into bone

Question 11

what is routine medical followup for conservatively treated parathyroidism?

Answer 11

• yearly Ca and Cr levels
• BMD assessments at spine, hip, and wrist every one or two
• adequate hydration and ambuation
• moderate Ca intake despite hypercalcemia (prevent further stimulation of PTH secretion)

Question 12

what is PTHrp (related peptide) associated with?

Answer 12

humoral factor secretion by squamous cell cancers and ovarian carcinomas
-PTH suppressed, PTHrP increased

Question 13

what do skeletal metastases release?

Answer 13

cytokines and factors that stimulate OC-mediated bone resorption

Question 14

what is familial hypocalcuric hypercalcemia? how does it differ from primary parathyroidism

Answer 14

AD mutation of Ca-sensing receptor

• mostly asymptomatic, with rarely elevated PTH
• urinary Ca collection is low in FHH, unlike primary hyperparathyroidism
• parathyroidectomies willbe unsuccessful

Question 15

what is milk alkali syndrome?

Answer 15

consumption of large amounts of Ca (Tums)

-rare now

Question 16

what medications can cause hypercalcemia?

Answer 16

• Li therapy (chronically increases set point for PTH –> mass)
• thiazides

Question 17

what are the levels of hypercalcemia and specific treatments?

Answer 17

mild (14) - life-threatening malignancy with immediate treatment (poor prognosis)

Question 18

what is the difference between secondary and tertiary hyperparathyroidism?

Answer 18

secondary: plasma Ca is normal/low
tertiary: plasma Ca is high

Question 19

what needs to be checked if low Ca is detected?

Answer 19

• albumin (may be normal if correcting for albumin)

- PTH (if low, it’s hypoparathyroidism; if high, it’s secondary hyperthyroidism)

Question 20

hormonally, what is renal failure caused by?

Answer 20

-limited excretion of phosphate and diminished hydroxylation of 25(OH)D to active calcitriol –> reduce absorption and resorption –> hypocalcemia –> stimulates PTH release

Question 21

why do you limit Ca++ intake when treating hypoparathyroidism?

Answer 21

keep it low-normal to prevent hypercalcuria (renal Ca retaining effect from PTH is lost; if combined with vit D, will have increased absorption and filtered load cleared by kidney, causing stones)

Question 22

what are causes for hypomagnesemia? clinical manifestations?

Answer 22

• loss of Mg from GIT, primary aldosteronism, hypercalcemia

- concomitant hypocalcemia, hypokalemia

Question 23

treatment for acute VS persistent hypocalcemia

Answer 23

acute: depends on severity; if symptomatic, give Ca gluconate (slow injection or steady infusion)
persistent: supplemental Ca and vit D

Question 24

what can hyperphosphatemia be caused by?

Answer 24

• increased intake of oral, phosphate enemas, or IV
• decreased renal excretion (failure, hypoparathyroidism)
• transcellular shift from intra to extracellular space (like hypophos)

Question 25

what are short-term VS long-term consequences of hyperphosphatemia?

Answer 25

short: hypocalcemia, tetany
long: tissue calcification, secondary hyperparathyroidism

Question 26

what are the abnormalities that cause hypophosphatemia

Answer 26

1. decreased intestinal absorption of phosphorus (starvation, malnutrition, vit D deficiency)
2. increased urinary losses (hyperparathyroidism, renal tubular defects, abnormal vit D metabolism, oncogenic osteomalacia, DKA, drugs)
3. transcellular shift from intra to extracellular space (like hyperphos)