Unit 5 - Parathyroids and Bone Flashcards
relationship between OPG/RANKL/RANK
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)
what are bone turnover markers?
formation: bone-specific alkaline phosphatase and osteocalcin
resorption: serum TRAP, serum/urine NTx and CTx
control and actions of PTH
- 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
how does Ca circulate in the plasma?
- ionized (50%); active
- protein-bound (40%); mostly to albumin
- complexed to bicarb, citrate, PO4
what does acidosis and alkalosis do to Ca binding to albumin?
acidosis: decreases binding (increases active ionized Ca), enhances tubular reabsorption
alkalosis: increases binding (decreases active ionized Ca), increases tubular clearance
what is the main determinant of intestinal absorption of Ca and P?
1,25-(OH)2D
who can get phosphorus deficiencies?
alcoholics and people taking antacids with Al (binds phosphate to prevent absorption; used to prevent hyperophosphatemia in renal failure)
how is Mg related to PTH?
it is necessary for its release, and for action of hormone on its target tissues
-if Mg low, PTH is stimulated and vice versa
what do furosemide and cisplatin do to Mg reabsorption?
inhibit reabsorption in LoH
what is “transient hypocalcemia” seen in?
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
what is routine medical followup for conservatively treated parathyroidism?
- 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)
what is PTHrp (related peptide) associated with?
humoral factor secretion by squamous cell cancers and ovarian carcinomas
-PTH suppressed, PTHrP increased
what do skeletal metastases release?
cytokines and factors that stimulate OC-mediated bone resorption
what is familial hypocalcuric hypercalcemia? how does it differ from primary parathyroidism
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
what is milk alkali syndrome?
consumption of large amounts of Ca (Tums)
-rare now
what medications can cause hypercalcemia?
- Li therapy (chronically increases set point for PTH –> mass)
- thiazides
what are the levels of hypercalcemia and specific treatments?
mild (14) - life-threatening malignancy with immediate treatment (poor prognosis)
what is the difference between secondary and tertiary hyperparathyroidism?
secondary: plasma Ca is normal/low
tertiary: plasma Ca is high
what needs to be checked if low Ca is detected?
- albumin (may be normal if correcting for albumin)
- PTH (if low, it’s hypoparathyroidism; if high, it’s secondary hyperthyroidism)
hormonally, what is renal failure caused by?
-limited excretion of phosphate and diminished hydroxylation of 25(OH)D to active calcitriol –> reduce absorption and resorption –> hypocalcemia –> stimulates PTH release
why do you limit Ca++ intake when treating hypoparathyroidism?
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)
what are causes for hypomagnesemia? clinical manifestations?
- loss of Mg from GIT, primary aldosteronism, hypercalcemia
- concomitant hypocalcemia, hypokalemia
treatment for acute VS persistent hypocalcemia
acute: depends on severity; if symptomatic, give Ca gluconate (slow injection or steady infusion)
persistent: supplemental Ca and vit D
what can hyperphosphatemia be caused by?
- increased intake of oral, phosphate enemas, or IV
- decreased renal excretion (failure, hypoparathyroidism)
- transcellular shift from intra to extracellular space (like hypophos)
what are short-term VS long-term consequences of hyperphosphatemia?
short: hypocalcemia, tetany
long: tissue calcification, secondary hyperparathyroidism
what are the abnormalities that cause hypophosphatemia
- decreased intestinal absorption of phosphorus (starvation, malnutrition, vit D deficiency)
- increased urinary losses (hyperparathyroidism, renal tubular defects, abnormal vit D metabolism, oncogenic osteomalacia, DKA, drugs)
- transcellular shift from intra to extracellular space (like hyperphos)
