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57 Cards in this Set

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What is the range of plasma Ca concentrations?
2.2-2.6 mM (very narrow)
What are the results of hypocalcemia?
Muscle failure, tetany, convulsions, death.
What are the results of hypercalcemia?
Renal dysfunction, muscle weakness, coma.
What is the level of intracellular Ca concentration?
100 μM
What will happen if intracellular Ca is increased for prolonged periods?
Ca-dependent proteases, nucleases, and lipases will cause cytodegradation.
What % of Ca is bound, and to what protein is it bound?
50%; albumin.
What is measured to estimate free Ca?
Albumin.
What are the results of severe hypophosphatemia?
Muscle weakness, abnormal bone formation.
What are the 3 points of regulation for Ca?
1) Intestine
2) Kidney
3) Bone
What are the 2 points of regulation for phosphate?
1) Kidney
2) Bone
How is the intestine affected by PTH?
No direct effect.
How is the intestine affected by Vit D?
Increase Ca absorption (primary action of Vit D) via active mechanisms.
*Vit D is the only steroid hormone that regulates Ca at the intestine.
How is the intestine affected by Calcitonin?
No known effect.
How is the kidney affected by PTH?
Increase Ca reABsorption
Decrease Phosphate reABsorption (increase Phosphate excretion)
*Remember, PTH wants to keep plasma Ca levels high, but in the case of the kidney, will release phosphate.
How is the kidney affected by Vit D?
Increase Ca absorption
Increase Phosphate reABsorption
How is the kidney affected by Calcitonin?
Increase Ca excretion
Increase Phosphate excretion
*Calctinonin wants to keep Ca levels in the plasma low.
How is bone affected by PTH?
Increase Ca resorption
Increase Phosphate resorption (primary purpose of PTH)
How is bone affected by Vit D?
Increase Ca resorption
Increase Phosphate resorption
(only during hypocalcemia, when Vit. D levels are extremely high; otherwise it will aid in bone formation.)
How is bone affected by Calcitonin?
Decreased Ca resorption/Increased Ca absorption (primary purpose).
What is ectopic PTH and what are its effects?
Cancerous hypersecretion of PTH that promotes bone resorption and hypercalcemia.
Why are canaliculi useful in the bone?
Canaliculi provide a large interface between mineralized bone and intracellular fluid for efficient bone remodeling to occur.
What are osteoclasts?
Chew bone for resorption, releasing Ca and phosphate into circulation.
What are osteoblasts?
Build bones - lay down osteoid to rebuild bone.
What 3 hormones will increase bone formation?
1) Vit D (mineralization occurs when within normal plasma range)
2) Calcitonin
3) PTH (intermittent, low levels)
What 2 hormones will increase bone resorption?
1) Vit D - at excessive levels
2) PTH (constant)
How will an increase in Ca affect PTH levels?
Drastic decrease because no bone resorption necessary.
How will a decrease in Ca affect PTH levels?
Drastic increase because because bone resorption is necessary to increase plasma Ca.
What is the result of PTH binding to bone cell receptors?
Bone resorption, releasing Ca and phosphate into the circulation.
*Remember, PTH wants to keep plasma Ca high.
What is the result of PTH binding to kidney receptors?
Stimulates Ca reabsorption, BUT increases phosphate excretion.
What is the general name for Vit D?
Calciferol.
What is cholecalciferol?
Form of Vit D3 found mostly in animals.
What is calcidiol?
25-OH-Vit D
What is calcitriol?
1,25-(OH)2-Vit D, active form.
Describe the endogenous pathway of 1,25-(OH)2-Vit D synthesis.
SLiK pathway - begins with skin Vit D formation by UV light, transport to the liver, and then to the kidney.
Describe the exogenous pathway of 1,25-(OH)2-Vit D synthesis.
Intestinal absorption of Vit D enters into the liver.
What is transcalciferin?
Transport globulin that binds Vit D in the plasma.
Also known as DBP.
How is Vit D status measured in patients?
Assays of 25-OH-Vit D because it is more stable, have high levels in the plasma, longer 1/2 life.
What is the inactive, storage form of Vit D?
24,25-(OH)2-Vit D
What are rickets?
Childhood softening of the bone due to Vit D deficiency.
How do Vitamin D Receptors (VDR) work?
Bind Vit D and then become transcription factors in the nucleus. They heterodimerize with RXR to increase or decrease transcription, depending on the target.
How is 1,25-(OH)2-Vit D regulated at the kidney level?
Low levels of Ca or Phosphate will produce more 1,25-(OH)2-Vit D.
Production of 1,25-(OH)2-Vit D is negative feedback for PTH because plasma Ca will already be high.
???
Describe passive intestinal absorption of Ca.
Passive absorption occurs paracellularly and is independent of 1,25-(OH)2-Vit D.
Describe active intestinal absorption of Ca.
Active absorption occurs transcellularly and is dependent on 1,25-(OH)2-Vit D.
Much more Ca is absorbed by active, transcellular absorption with Vit D.
How does Ca get from the intestinal lumen to the blood stream?
Via the Ca binding protein, calbindin.
What is the result of Vit D binding to VDR on the parathyroid?
Suppresses PTH secretion (PTH tries to raise plasma Ca) as negative feedback.
What promising benefit does activated VDR seem to have?
Anti-proliferative, pro-apoptotic signals to tumor cells.
Where is Calcitonin produced?
In parafollicular "C" cells of between thyroid follicles.
What hormone stimulates the release of Ca postprandially?
Gastrin to prevent diet-induced hypercalcemia.
What is the effect of calcitonin on the bone?
Increases bone formation by absorbing Ca and phosphate, decreasing their levels in the circulation.
What is the effect of calcitonin on the kidney?
Increase phosphate excretion.
What is the relationship between PTH and Calcitonin?
Inversely related.
Vit D, Calcitonin, PTH: which of these are nonessential for human survival?
Calcitonin.
What enzyme is responsible for activating Vit D
[25-OH-Vit D3 --> 1,25-(OH)2-Vit D3]?
1-α-hydroxylase, which occurs in the kidney.
*Obviously this must be a 1-hydroxylase by looking at the product.
What factors cause conversion of 25-OH-Vit D to active 1,25-(OH)2-Vit D3?
Any Ca, phosphate, or Vit D deficiency, and an increase in PTH secretion.
What factors cause conversion of 25-OH-Vit D to inactive 24,25-(OH)2-Vit D3?
Any Ca, phosphate, or Vit D sufficiency or excess.
How does Ca homeostasis respond to a state of hypocalcemia?
PTH levels will increase, plasma Ca will increase, Vit D will increase, and phosphate will be excreted out through the kidney.
Once levels normalize, PTH and Vit D will decrease to normal levels. Both are regulated by plasma Ca levels.
How does phosphate homeostasis respond to hypophosphatemia?
Vit D will increase, intestinal absorption of phosphate will increase, bone resorption of phosphate will increase, a subsequent increase in Ca will suppress PTH, which will decrease kidney excretion of phosphate, and plasma phosphate levels will be restored. Vit D will return to normal levels once plasma phosphate normalizes.