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calcium regulation
ENDO
41
Medical
Graduate
12/03/2010

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Term
where is 99% of Ca2+ stored?
Definition
in the bones
Term
what does endocrine regulation of extracellular Ca2+ affect?
Definition
entry at the kidneys, exit at the kidney, and regulation of the skeletal reservoir
Term
what characterizes the daily turnover for Ca2+?
Definition
~ 800 mg is taken in daily and ~ 800 mg is lost daily. 300 mg is absorbed into the blood and 500 mg goes directly the feces. additionally, 150 mg is lost in sloughed off intestinal cells and 150 mg is excreted by the kidneys. *this means in order to have any effect on raising Ca2+ levels, a significant amount of supplemental Ca2+ is necessary.
Term
what characterizes intestinal absorption of Ca2+?
Definition
Ca2+ is absorbed via active vit D-dependent transport in the proximal duodenum (facilitated diffusion) and efficiency of this transport is inversely related to Ca2+ intake. the level of absorption decreases w/age, glucocorticoids, phytate, oxylate and phenytoin. diseases states can also lead to fecal loss of Ca2+.
Term
what characterizes urinary regulation of Ca2+?
Definition
urinary excretion:reabsorption of Ca2+ is regulated by PTH minute to minute and is also influenced by filtered Na+. diuretics such as ethacrynic acid, furosemide, and thiazide diuretics will increase Ca2+ loss.
Term
can Ca2+ be lost via lactation and sweat?
Definition
yes
Term
what is the final common pathway through which bone mass is adjusted?
Definition
bone remodeling via osteoclasts/blasts
Term
what factors influence bone remodeling?
Definition
hyperthyroidism, hypervitaminosis D, and hyperparathyroidism all *increase the activation of remodeling units. high doses of corticosteroids or ethanol will *impair osteoblastic functional adequacy. decreased estrogen will *augment osteoclastic resorptive capacity.
Term
what are the pathologic conditions of Ca2+?
Definition
hyper/hypocalcemia
Term
what characterizes hypocalcemia?
Definition
hypocalcemia is promoted by combined deprivation of Ca2+ and vit D. hypocalcemia stimulates PTH release which then increases bone remodeling = more Ca2+ being released into the blood+extracellular fluid.
Term
what are the s/s for hypocalcemia?
Definition
tetany, paraesthesias, increased neuromuscular excitability, laryngospasm, muscle cramps, and tonic-clonic convulsions (grand mal).
Term
what are some situations which may lead to a hypocalcemic state?
Definition
hypoparathyroidism, advanced renal insufficiency, excessive use of potassium phosphate in DKA tx, large quantities of sodium fluoride, and massive transfusions of citrated blood.
Term
what is tx for hypocalcemia?
Definition
dietary Ca2+ : IV if severe or oral supplements w/vit D
Term
what are some different causes for a hypercalcemic state?
Definition
high ingestion of Ca2+ (rare, except in hypothyroidism), hyperparathyroidism (most common outpt), familial benign hypercalcemia, vit D excess, or systemic malignancy (common in hospital pts)
Term
how is hypercalcemia treated?
Definition
fluids (6-8 L/day), loop diuretics (increased Ca2+ excretion), corticosteroids, calcitonin, plicamycin, IV bisphosphonates, gallium nitrate, oral sodium phosphate, and edetate disodium
Term
what are the major substances involved w/Ca2+ regulation?
Definition
phosphate, parathyroid hormone (PTH), vit D, and calcitonin (CT)
Term
what happens when PTH goes up and CT goes down?
Definition
bone resorption of Ca2+ increases, intestinal absorption of Ca2+ increases, vit D increases, and urinary phosphate increases. serum phosphate decreases and renal excretion of Ca2+ decreases.
Term
what happens when PTH goes down and CT goes up?
Definition
serum phosphate increases and renal Ca2+ excretion increases. bone resorption decreases, vit D decreases, urinary phosphate decreases, and intestinal absorption decreases
Term
what characterizes phosphate and its interactions w/Ca2+?
Definition
phosphate is absorbed from the GI tract and reabsorbed from the proximal tubules in the kidney due to vit D stimulation. PTH increases urinary phosphate (blocks reabsorption) which allows for higher serum Ca2+ levels as *decreased serum phosphate permits more spaces for serum Ca2+.
Term
what are the pathologic states of phosphate?
Definition
rickets (vit D deficiency), osteomalacia, primary/secondary hyperparathyroidism, and chronic renal failure.
Term
what is the primary function of PTH?
Definition
to maintain a constant concentration of Ca2+ in the extracellular fluid via regulation of intestinal Ca2+ absorption, mobilization of bone Ca2+, and excretion of Ca2+ in urine/feces/sweat/milk.
Term
what characterizes PTH secretion?
Definition
low serum Ca2+ levels (high Ca2+ levels decrease PTH secretion). the response of PTH to Ca2+ levels occurs w/in minutes.
Term
what is the effect of PTH on bone?
Definition
PTH increases overall bone resorption
Term
what is the effect of PTH on the kidney?
Definition
PTH enhances the efficiency of Ca2+ reabsorption, inhibits tubular reabsorption of phosphate, and stimulation of vit D to hormonal form (1,25 dihydroxy-vitamin D or calcitriol)
Term
what is the end result of PTH secretion?
Definition
filtered Ca2+ is avidly retained, Ca2+ plasma concentration increases, calcitriol is secreted into circulation, and calcitriol contributes to increased GI Ca2+ absorption (= increased serum Ca2+ levels).
Term
what characterizes the role of vit D3 (1,25 dihydroxy...) in Ca2+ regulation? phosphate regulation?
Definition
vit D3 is synthesized in the skin and kidneys and binds to receptors in target tissues, *ultimately resulting in increased plasma Ca2+. vit D maintains normal Ca2+ AND phosphate levels in the plasma by facilitating their absorption by the small intestine, interacting w/PTH to enhance their mobilization from bone, and decreasing their excretion by the kidney.
Term
what is the role of calcitonin in Ca2+ regulation?
Definition
calcitonin secretion is increased when serum Ca2+ levels are high and decreased when serum Ca2+ levels are low (synthesis and release is Ca2+ dependent). glucagon, gastrin, and serotonin can also increase calcitonin levels. the circulating half-life of calcitonin is ~10 min.
Term
what is the mechanism of calcitonin action?
Definition
direct inhibition of osteoclastic bone resorption = hypocalcemia and hypophosphatemia (bone is composed of both calcium+phosphate, therefore inhibiting its breakdown = lower blood levels of both). calcitonin also stimulates formation of bone by osteoblasts.
Term
what is the effect of administrating exogenous calcitonin?
Definition
lower serum Ca2+ and phosphate levels. a single dose lasts 6-10 hours.
Term
what is the general MOA of the bisphosphonates such as etidronate and pamidronate?
Definition
inhibition of bone resorption via incorporation into bone matrix and incapacitation of osteoclasts.
Term
what is the specific MOA of the bisphosphonate alendronate?
Definition
inhibition of osteoclast-mediated bone resorption via preferential localization to the site of bone resorption. bone turnover in postmenopausal pts taking alendronate is roughly equivalent to that in premenopausal (estrogen inhibits bone turnover).
Term
what ADRs are associated w/alendronate?
Definition
mild GI, bone/muscle/joint pain, and muscle cramps. this drug needs to be taken on an empty stomach and the pt needs to remain upright at least 30 min to avoid any worse ADRs (if the pt is recumbent = esophageal problems).
Term
what is raloxifine?
Definition
a SERM (selective estrogen receptor modulator) which blocks estrogen pathways to the uterus/breast and activates them to the bone = reducing bone turnover as well as decreasing total cholesterol and LDL. (HDL and triglycerides are unaffected)
Term
what ADRs are associated w/raloxifine?
Definition
flu-like syndrome, hot flashes, general GI, and arthralgia
Term
what is alendronate used for?
Definition
postmenopausal osteoporosis
Term
what is calcitonin used for?
Definition
paget's disease, postmenopausal osteoporosis, and hypercalcemia of malignancy
Term
what is calcitriol used for?
Definition
metabolic bone disease for renal failure
Term
what are dihydrotachysterol and ergocalciferol used for?
Definition
vit D replacement
Term
what is etidronate used for?
Definition
paget's disease and postmenopausal osteoporosis
Term
what is pamidronate used for?
Definition
hypercalcemia of malignancy
Term
what is raloxifene used for?
Definition
postmenopausal osteoporosis
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