Term
| where is 99% of Ca2+ stored? |
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Definition
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Term
| what does endocrine regulation of extracellular Ca2+ affect? |
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Definition
| entry at the kidneys, exit at the kidney, and regulation of the skeletal reservoir |
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Term
| what characterizes the daily turnover for Ca2+? |
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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. |
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Term
| what characterizes intestinal absorption of Ca2+? |
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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+. |
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Term
| what characterizes urinary regulation of Ca2+? |
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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. |
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Term
| can Ca2+ be lost via lactation and sweat? |
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Definition
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Term
| what is the final common pathway through which bone mass is adjusted? |
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Definition
| bone remodeling via osteoclasts/blasts |
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Term
| what factors influence bone remodeling? |
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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. |
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Term
| what are the pathologic conditions of Ca2+? |
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Definition
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Term
| what characterizes hypocalcemia? |
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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. |
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Term
| what are the s/s for hypocalcemia? |
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Definition
| tetany, paraesthesias, increased neuromuscular excitability, laryngospasm, muscle cramps, and tonic-clonic convulsions (grand mal). |
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Term
| what are some situations which may lead to a hypocalcemic state? |
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Definition
| hypoparathyroidism, advanced renal insufficiency, excessive use of potassium phosphate in DKA tx, large quantities of sodium fluoride, and massive transfusions of citrated blood. |
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Term
| what is tx for hypocalcemia? |
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Definition
| dietary Ca2+ : IV if severe or oral supplements w/vit D |
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Term
| what are some different causes for a hypercalcemic state? |
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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) |
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Term
| how is hypercalcemia treated? |
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Definition
| fluids (6-8 L/day), loop diuretics (increased Ca2+ excretion), corticosteroids, calcitonin, plicamycin, IV bisphosphonates, gallium nitrate, oral sodium phosphate, and edetate disodium |
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Term
| what are the major substances involved w/Ca2+ regulation? |
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Definition
| phosphate, parathyroid hormone (PTH), vit D, and calcitonin (CT) |
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Term
| what happens when PTH goes up and CT goes down? |
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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. |
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Term
| what happens when PTH goes down and CT goes up? |
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Definition
| serum phosphate increases and renal Ca2+ excretion increases. bone resorption decreases, vit D decreases, urinary phosphate decreases, and intestinal absorption decreases |
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Term
| what characterizes phosphate and its interactions w/Ca2+? |
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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+. |
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Term
| what are the pathologic states of phosphate? |
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Definition
| rickets (vit D deficiency), osteomalacia, primary/secondary hyperparathyroidism, and chronic renal failure. |
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Term
| what is the primary function of PTH? |
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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. |
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Term
| what characterizes PTH secretion? |
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Definition
| low serum Ca2+ levels (high Ca2+ levels decrease PTH secretion). the response of PTH to Ca2+ levels occurs w/in minutes. |
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Term
| what is the effect of PTH on bone? |
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Definition
| PTH increases overall bone resorption |
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Term
| what is the effect of PTH on the kidney? |
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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) |
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Term
| what is the end result of PTH secretion? |
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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). |
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Term
| what characterizes the role of vit D3 (1,25 dihydroxy...) in Ca2+ regulation? phosphate regulation? |
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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. |
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Term
| what is the role of calcitonin in Ca2+ regulation? |
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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. |
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Term
| what is the mechanism of calcitonin action? |
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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. |
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Term
| what is the effect of administrating exogenous calcitonin? |
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Definition
| lower serum Ca2+ and phosphate levels. a single dose lasts 6-10 hours. |
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Term
| what is the general MOA of the bisphosphonates such as etidronate and pamidronate? |
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Definition
| inhibition of bone resorption via incorporation into bone matrix and incapacitation of osteoclasts. |
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Term
| what is the specific MOA of the bisphosphonate alendronate? |
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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). |
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Term
| what ADRs are associated w/alendronate? |
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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). |
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Term
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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) |
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Term
| what ADRs are associated w/raloxifine? |
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Definition
| flu-like syndrome, hot flashes, general GI, and arthralgia |
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Term
| what is alendronate used for? |
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Definition
| postmenopausal osteoporosis |
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Term
| what is calcitonin used for? |
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Definition
| paget's disease, postmenopausal osteoporosis, and hypercalcemia of malignancy |
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Term
| what is calcitriol used for? |
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Definition
| metabolic bone disease for renal failure |
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Term
| what are dihydrotachysterol and ergocalciferol used for? |
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Definition
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Term
| what is etidronate used for? |
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Definition
| paget's disease and postmenopausal osteoporosis |
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Term
| what is pamidronate used for? |
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Definition
| hypercalcemia of malignancy |
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Term
| what is raloxifene used for? |
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Definition
| postmenopausal osteoporosis |
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