three forms of calcium in extracellular compartment
1. ionized Ca2+ - 50% (MET. ACTIVE) 2. bound to albumin - 40% 3. complexed with anions such as citrate and phosphate - 10%
total calcium measurement has to be adjusted ...
for every 1g/dL of serum albumin that deviates from 4mg/dL -> causes a 0.8 mg/dL variation in calcium
two main hormones involved in calcium metabolism
1. PTH 2. 1,25-hyhydroxy vit D
target organs of the hormones that regulate Ca
bone kidney intestines
what the most important hormone for Ca regulation
PTH -changes in serum Ca level will increase or decrease the levels PTH in a matter of minutes
low Ca levels will cause inc or dec secretion of PTH?
how does the parathyroid know what the Ca levels are?
calcium sensing receptors
what is necessary for noraml secretion of PTH?
normal serum Mg
PTH effects on bone
-stimulates bone turnover, activation of osteoclasts ->results in release of Ca into the circulation
effects of PTH on kidneys
1)inc reabsorption in the distal tubules 2)dec phosphate reabsorption in prox tubules 3) stimulation of the renal cortical enzyme 1-ALPHA-HYDROXYLASE which causes: 25-hydroxy vit D ->to active 1,25 dihydroxy vit D -this leads to inc absorption of Ca and PO in the gut
effects of PTH on intestines
indirect effect by increasing 1,25 dihydroxy vit D -> inc Ca and PO in gut
how does vit D get into the curculation?
-oral ingestion -via conversion of 7-dehydrocholestrol -> vit D via UV light
what happens to vit D from sun light?
in the liver it is converted to 25-hydroxy vit D then in the renal cprtex it is converted to 1,25-dihydroxy vit D
what enzyme? and where? vit D (cholicalciferol) -> 25-hydroxy vit D
what enzyme? and where? 25-hydroxy vit D -> 1,25 dihydroxy vit D
1- alpha-hydroxylase (renal cortex)
which form of vit D is active and what does it do?
1,25 dihydroxy vit D
-promotes Ca absorption in the gut -dec PTH synthesis -promotes PO absoption from gut
which vit D do we test?
25-hydroxy vit D
what is the difference between PTH and active vit D?
PTH -> inc Ca and dec PO Vit D-> inc Ca and inc PO
more than 10.2mg/dL
most common presentation of hypercalcemia
LAB FINDINGS most pts don't have syms until total Ca is over 12 md/dL definitly have syms over 14 mg/dL
decreased perception of calcium by the calcium sensing receptors on the parathyroid gland and in teh kidney
- NO SURGERY! low calcium in the urine
there is almost always underlying renal dz MORE INFO
causes of primary hyperparathyroidism (HPT)
70-80% of ppl are asymp 3: women:men
80% single parathyroid adenoma 15% have 4-gland hyperplasia 0.5% parathyroid carcinoma
tx for primary HPT
surgery is the only definitive treatment 95% sucess rate
indication for surgery for HPT
1. serum Ca >1mg/dL above upper limit of normal 2.presence of sign or symptoms of hypercalcemia 3. urine calcium >400 mg/24hrs 4. creatine clearance reduced below #0% of age0matched normal 5. decreased bone mineral density 6. pt under 50 7.vit D deficncy (not part of the national recommendations)
1. direct bony met 2. elaboration of PTHrP 3. cytokine production associated with osteoclast activation: lymphotoxin, transforming growth factors, interlukins, TNF, 4. in creased active vit D production (lymphoma)
peptide responsible for the syndrome HHM (humoral hypercalcemia of malignancy) -frequenctly with squamous cell cancers, renal cell and breast cancers -PTH level suppressed for degree of hyper-Ca -PTHrP mimics many of the bio actions of PTH but does NOT stimulate renal hydroxylase therfore NO increase in vit D
intact PTH: high 1,25 vit D level: high phosphorus: normal or low PHTrP: low
dd of hypercalcemia:
intact PTH: low 1,25 vit D level: normal or low phosphorus: normal or low PHTrP: high
dd of hypercalcemia:
intact PTH: normal or low 1,25 vit D level: high phosphorus: high PHTrP: low
tx of hypercalcemia
1st: enhance renal Ca excretion-> lasix and IV fluid 2nd: inhibit bone resorption (inhibit oseoclasts) ->calcitonin ->mithramycin-a cytotoxic ABX that inhibits RNA syn thereby inhibiting osteoclasts (not used very often b/c of toxicity) ->bisphosphonates 3rd: inhibit gut absorption -> glucocorticoids other: oral phosphate therapy
most common outpt cause of hypercalcemia
most common inpt cause of hypercalcemia
serum PTH is low or high in malig-assoc hypercalcemia