Term
| what is an ideal Ca++ intake for an adult? |
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Definition
| 900 mg/day - which equals daily Ca++ loss |
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Term
| why is accumulation of Ca++ bad? |
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Definition
| calcium has to be deposited somewhere else other than the bone, and it can even to hypercalcemia |
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Term
| what is the optimum Ca++ serum level for the body? |
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Definition
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Term
| what can hypercalcemia lead to? |
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Definition
| decreased mental status, kidney injury, calcium deposits all over the body |
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Term
| what can hypocalcemia lead to? |
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Definition
| irritability of the nerves, seizures, muscle cramping, potentially hypotension |
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Term
| what is the goal of calcium regulation in the body? |
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Definition
| to maintain intracellular Ca++ at a low level (a few micro mol) and extracellular Ca++ at a narrow range (1 mmol) |
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Term
| where does vit D come from? what is the role of vit D in calcium regulation? |
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Definition
| 1,25 - dihydroxy-vit D is a vitamin produced in the skin that has to be processed in the liver and kidney to become activated. activated vit D allows you to absorb Ca++ across your small bowel. |
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Term
| what is serum Ca++ in equilibrium with? why? |
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Definition
| bone, which needs to be renewed constantly - or else it becomes weak due to microfractures which occur all the time |
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Term
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Definition
| favoring the bone breakdown side of the Ca++ equilibrium - happens most often to older women w/northern european backgrounds |
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Term
| what regulates Ca++ levels? |
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Definition
| PTH, via the Ca++ sensing receptor in the neck (may be the only known protein that sense the level of ion in the blood) |
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Term
| how does the PTH regulated Ca++ levels? |
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Definition
| whenever the serum Ca++ falls (even a little), it released PTH. it will *favor bone breakdown* over formation as the Ca++ released to maintain serum levels comes from the bone |
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Term
| what would be the result of an extended lack of Ca++ intake on a pt? |
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Definition
| a little Ca++ would be lost through urine and stool, dropping the serum level slightly over time - which would then be compensated for by PTH release, which would take Ca++ from the bone to replace the lost serum Ca++. over an extended period, this could result in hyperparathyroidism and markedly reduced bone mass |
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Term
| what is the link between phosphorus and Ca++? what is the implication of this? |
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Definition
| calcium and phosphorus combined create the crystalline material of bone - therefore phosphorus has to create an equilibrium w/bone in the same fashion as Ca++ (bone is breaking down and releasing phosphorus, while new phosphorus comes in) |
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Term
| how important is phosphorus in the body? |
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Definition
| very - remember all the regulation rxns - cyclic AMP, protein kinase C, tyrosine kinases, etc |
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Term
| is phosphorus absorption dependent on vit D? |
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Definition
|
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Term
| what should conc serum phosphorus be? intracellular? |
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Definition
| serum: about 1 mmol/L or about 3 mg/dL. intracellular: about 100 mmol/L |
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Term
| what is one of the major problems with chronic kidney disease? |
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Definition
| high levels of phosphorus are ingested, but the kidney is the only way to get rid of it, so if the kidneys are not working correctly - excess phosphorus combines with calcium and precipitates in deposits found in bone, muscle or soft tissue |
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Term
| how can high phosphorus levels be associated with CV disease? |
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Definition
| excess phosphorus combines with calcium and creates deposits in the vasculature - which is a major problem for CKD pts who can't secrete phosphorus |
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Term
| is phosphorus retention in patients with kidney disease an important cause of vascular disease in patients with renal insufficiency? |
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Definition
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Term
| what is the normal range for serum phosphorus? is the upper range associated with CV disease? |
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Definition
| 2.5-4.5, and the upper range is associated with CV disease |
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Term
| what does the vascular stiffness associated with renal failure/high serum phosphorus do to the heart? |
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Definition
| make it work harder - can result in CHF ultimately |
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Term
| what does vit D metabolism consist of? |
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Definition
| vit D exists as 7-dihydrocholesterol in the skin and transformed into cholecalciferol under the influence of UV light. cholecalciferol is then transported to the liver where it gains a -OH group, becoming 25-hydroxycholecalciferol which gets transported to the kidney. in the kidney, a second hydroxyl group gets added on and now you have the active form of vit D in the body (1,25-hydroxycholecalciferol). |
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Term
| how does kidney disease cause a problem w/vit D, phosphorus and Ca++ levels? |
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Definition
| if the kidneys are not functioning correctly, active vit D is not being produced, and Ca++ cannot be absorbed from the small bowel. this causes serum phosphorus levels to increase (=CV disease) and serum Ca++ levels to decrease (= PTH levels increase, leading to hyperparathyroidism) |
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Term
| is vit D needed for PTH to work on bone? |
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Definition
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Term
| in summary, what are the main effects of kidney failure on Ca++, phosphorus, and vit D levels? |
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Definition
| phosphorus accumulates (Ca-PO4 deposits = CV disease and lower serum Ca++) and the body is chronically vit D deficient (less Ca++ reabsorbed from the small bowel, less Ca+ released from the bone, lower serum Ca++ levels, and PTH levels increase) |
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Term
| virtually everyone that has chronic renal disease has secondary ____________ |
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Definition
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Term
| what can cause primary hyperparathryoidism? |
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Definition
| an adenoma of the PT glands - generally benign, the pt just makes too much PTH |
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Term
| what do pts with PT adenomas look like? |
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Definition
| hypercalcemia, high vit D levels (high PTH increases vit D activation), low phosphorous (*PTH tells kidney to increase PO4 excretion, which further raises serum Ca++ b/c it has nothing to bind to - accomplishes goal of PTH, to raise serum Ca++) |
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Term
| what happens in pts with no kidney and hyperparathyroidism? |
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Definition
| bone breakdown, no vit D production, no excretion of phosphorus |
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Term
| what is the effect of osteodystrophy on the vertebrae called? |
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Definition
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Term
| what happens to the clavicle in renal osteodystrophy? |
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Definition
| the distal third becomes radiolucent |
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Term
| what goes wrong in early renal disease? |
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Definition
| abnormal Ca++ metabolism. abnormal phosphate metabolism. abnormal vit D metabolism. abnormalities of PTH secretion. abnormal skeletal response to PTH. |
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Term
| what are the main efects of renal disease on the Ca++/PO4/vir D balance? |
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Definition
| PO4+Ca->CaPO4, kidney -> vit D deficient, vit D deficient -> hypocalcemia, low Ca -> hyperparathyroidism |
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Term
| what are factors that influence PTH secretion? |
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Definition
| 1) Ca++ sensing receptor on the surface of PT cells 2) vit D receptor in the cell PT nucleus 3) putative sensor of serum PO4 level 4) parathyroid mass (more cells = more PTH) |
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Term
| what are the 2 regulatory pathways control the PT gland's release of PTH? |
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Definition
| high Ca++ levels shut off PTH *secretion via the PT gland's Ca++ receptor. high vit D levels shut off PTH *production, which it can do as a steroid hormone that activates a nuclear receptor, altering gene translation |
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Term
| what are characteristics of (secondary) hyperparathyroidism in early renal disease? |
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Definition
| normal serum PO4 (only normal b/c PTH is pushing its excretion, otherwise it would be retained), low/normal Ca++ (due to higher PTH, not absorption), low 1,25 vit D levels (due to FGF-23 accumulation, not kidney atrophy), and high PTH |
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Term
| what are characteristics of (secondary) hyperparathyroidism in advanced renal disease? |
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Definition
| elevated serum phosphate (calcium-phosphate deposits), low serum Ca++, very low 1,25, vit D, and very high PTH (sometimes insuppressible) |
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Term
| what are abnormalities in Ca++ metabolism in early renal failure? |
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Definition
| decreased Ca++ intake (endemic), and decreased Ca++ absorption |
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Term
| what are abnormalities in Ca++ metabolism in late renal failure? |
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Definition
| abnormalities in receptor density and function in the PT gland. depressed serum Ca++ (late w/hyperphosphatemia and skeletal exhaustion or skeletal resistance to PTH-action to mobilize Ca++) |
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Term
| how can PO4 retention stimulate PTH release in late renal disease? |
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Definition
| 1) PO4 uses up serum Ca++ to make CaPO4, causing the PT to secrete more PTH. 2) vit D activation is inhibited by PO4 |
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Term
| why do vit D levels fall in early renal disease? |
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Definition
| not b/c of kidney atrophy, but b/c of fibroblast growth factor-23 (FGF-23) that accumulates in early renal disease *suppresses vit D levels* . FGF-23 is made in bone and seems to be a factor that helps the kidney excrete its PO4 load. this substance accumulates higher the closer you get to ESRD. there is also a correlation between high FGF-23 levels and CV mortality. |
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Term
| what are the effects of late renal failure in terms of Ca++/PO4 levels and hyperparathyroidism? |
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Definition
| there are low levels of vit D/calcitriol associated with accumulation of FGF-23. there is PO4 retention and hypocalcemia. this will all lead to hyperparathyroidism. |
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Term
| how is the PT gland affected grossly by renal failure? |
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Definition
| early one there is diffuse stimulation of proliferation b/c you have less vit D and more stimulation of PTH. later in renal failure, nodules form that have less of the Ca++ sensing receptors and are less sensitive to vit D(which remain even if Ca++ levels return to normal). this continues the hyperparathyroidism problem. |
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Term
| how is soft tissue affected by renal disease? |
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Definition
| phosphate retention leads to its binding with Ca++, to form CaPO4 deposits that cause vascular occlusion leading to necrosis of the skin, destruction of heart tissue, etc |
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Term
| how is soft tissue accumulation of CaPO4 in ESRD pts treated? |
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Definition
| give Ca++ binders with meals that bind PO4 in the GI tract, preventing it from being absorbed. but these pills usually result in poor compliance so pts are educated to eat fresh food which has less PO4. they also need adequate amounts of vit D and Ca++ in their diet. |
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Term
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Definition
| a drug that binds to the calcium sensing receptor and makes the PT gland think that there is plenty of calcium in the ECF and shuts off PTH secretion |
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