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42 Cards in this Set
- Front
- Back
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Name 3 hormones involved in regulating calcium metabolism
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1) 1,25 DHCC - steroid hormone from vitamine D. Increase Ca absorption from intestine
2) PTH - secreted by parathyroid gland; mobilizes Ca from bone and increases phosphate excretion 3) Calcitonin - calcium lowering hormone secreted by cells in thyroid gland; inhibits bone resorption |
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What leads to hypocalcemic tetany?
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Low calcium concentration increases nerve and muscle cell excitability
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What leads to hypercalcemia?
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high plasma calcium that causes cardiac arrhythmia and depresses neuromuscular excitability
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How is calcium balanced achieved in an individual?
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99% Ca is stored in bone. Avg. intake is 600-1000 mg/day; net gain of 0.175 g in body is offset by equal loss in kidney via urine. Amt absorbed by gut decreases as one gets older
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Ca regulation in bone
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500 mM in rapidly exchangeable pool while 25,000 mM is in stable pool. plasma Ca regulated by the 2 pools + bone remodeling via constant resorption + deposition
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Ca regulation in kidney 2) Ca in GI tract
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1) large amt is filtered, 98-99% reabsorbed 2) active transport via Ca-dep ATPase regulated by 1,25 (OH)2D3
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How do osteoblasts promote calcium phosphate crystallization?
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Osteoblasts secrete alkaline phosphatase during mineralization. This cleaves PP, which reduces stabilization, and increases P to add to Ca.
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Why can osteoclasts dissolve mineral crystals?
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Secrete acids and proteases
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Describe the synthesis of the hormone 1,25(OH)2D3
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1) Vit D made by UV light on 7-dehydrocholesterol in skin
2) transport Vit D form skin through plasma and go to liver 3) Vit D3 hydroxlyation at 25 position and returns to blood 4) In renal prox tubules- 25OHD3 is further hydroxylated at 1 position 5) create 1,25(OH)2D3 |
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What is 1,25(OH)2D3 production stimulated by?
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PTH, hypocalcemia, and hypophosphatemia. PTH via action on enhancing phosphate diuresis, decreases intracellular P in kidney, and results in increased 1,25(OH)2D3.
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Describe actions of 1,25(OH)2D3
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formed in kidney, and travels through blood and effects GI tract and other organs
2) binds cytoplasmic receptor and forms VDR complex 3) VDR moves to nucleus, changes DNA transcirption, and creates Ca binding proteins (CaBP) |
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What is 1,25(OH)2D3 a potent inhibitor of?
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Inhibits proliferation of cells that have VDR.
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How does 1,25(OH)2D3 act in GI tract?
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Increase Ca pumping out of basolateral membranes in intestines
2) increase P and Ca uptake via 1,25(OH)2D3 induced increases in epithelial Ca channels (ECaC) + intracellular calcium binding proteins (Calbindin) 3) increase alkaline phosphatase activity leads to increase P uptake |
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How does 1,25(OH)2D3 act in bone?
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Increase pumping of Ca and P via osteoblasts + increase Ca and P indirectly via promoting absorption in gut
2) also acts indirectly to promote osteoclasts |
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How does 1,25(OH)2D3 act in kidney?
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Facilitate Ca reabsorption in kideny in proximal and distal nephron via ECaC + Calbindin. Enhance P uptake from tubular fluid in proximal nephron
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How is 1,25(OH)2D3 regulated?
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Plasma Ca and P regulate it by negative feedback of 1alpha-hydroxylase. Enzyme synthesis is stimulated by high PTH and low P.
Neg feedback via 1) P and Ca in plasma 2) 1,25(OH)2D3 overproduction on 1alpha-hydroxylase 3) positive feedback via stimulation of 24-hydroxylase + production of 24,25(OH)2D3 maybe leading to degradative pathway |
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Describe PTH synthesis + breakdown
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Pre-pro hormone stored in chief cells of parathyroid.
1) go to ER cleave to Pro-PTH 2) secrete PTH (1/2 life 20 min) Breakdown 1) take up by Kupfer cells of liver. 2) secrete as C terminal and N terminal fragments |
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How do the parathyroid glands monitor Ca?
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via Calcium sensor in blood (7-transmembrane receptor). Low Plasma Ca trigger Ca sensor in chief cells and through signal transduction, increase PTH gene and PTH secretion in blood
2) High Ca means PTH is no longer made or secreted |
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How does PTH affect bone?
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Stimulates RANKL expression on osteoblasts. RANK is on osteoclasts. RANK/RANKL interaction promotes preosteoclasts to become multinucleated giant osteoclast.
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How does body regulate preosteoclasts interaction osteoblasts RANKL?
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Regulates by producing soluble ligan called OPG. This blocks RANKL and prevents it from activating RANK.
1) estrogens enhance OPG and depress RANKL 2) cortisol inhibits OPG production. |
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What's the short term effect of PTH?
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Osteoclastic and osteoblastic activity increase, but bone resorption predominates
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What's the effect of PTH on kidney?
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PTH increases Ca in distal nephron, inhibits reabsorption of P in proximal tubule. with high PTH levels (primary hyperparathyroidism), increases in plasma Ca leading to increased filtered Ca load can exceed tubular reabsorption threshold + causes rise in urine Ca.
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How are Mg and PTH related?
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Low MG or very high Mg will inhibit PTH. Mg deficiency lowers Na-K-ATPase activity
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How is PTH secretion regulated?
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Ca increases leads to PTH inhibition; Ca deposited in bone; Ca decreases leads to PTH increase, and more Ca is mobilized from bone.
2) 1,25(OH)2D3 acts on PT gland by decreasing pre-pro PTH production 3) chronic kidney disease there is less 1,25(OH)2D3, means low plasma calcium leading to overstimulation of PT gland, and secondary hyperparathyroidism |
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What are the results of parathyroidectomy?
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Occurs by accidental removal of thyroid gland; increase plasma P but PTH injections can correct chemical abnormalities, Ca injections also provide temporary relief
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What does PTH excess result in?
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Tumor of PT gland leads to hyperparathyroidism.
1) hypercalcemia (cardiac arrhythmia) 2) hypophosphatemia (P excreted in excess) 3) demineralization of bones (increase bone resorption) 4) hypercalciururia 5) Ca containing stones |
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Describe actions of calcitonin
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1) decrease plasma Ca and P by decreasing bone resorption via acts on calcitonin receptors on osteoclasts,
2) increases Ca excretion in urine maybe more active in kids w/ bone formation, protects against post-prandial Ca increase |
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How do glucocorticoids effect Ca balance?
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Result in negative Ca balance.
1) decrease absorption of Ca by kidney 2) hypocalcemia that results is corrected by PTH. BUT glucocorticoids inhibit osteoblast formation, so balance is shift toward bone resorption. |
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How does GH affect Ca?
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Increases it via intestinal absorption
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How do T3 and T4 affect Ca?
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Increases it via increasing bone resorption
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How does estrogen affect Ca?
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Decrease osteoporosis by counteracting PTH effect on bone and promoting its effect on kidneys
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What increases permeability to Ca in osteoblasts? Decreases it?
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PTH increases it in osteoblasts; CT decreases it
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What inhibits 1 alpha-hydroxylase?
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1) negative feedback of 1,25(OH)2D3
2) free phosphate from bone |
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Describe the relationship between PTH and Mg
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PTH is synthesized all the time but is kept in low quantities. Low Mg will decrease PTH synthesis, and high Mg will decrease PTH secretion since it competitively inhibits the Calcium sensor receptor on chief cell
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In the kidneys, PTH acts to increase Ca reabsorption. What must also occur in the kidneys to ensure that Ca is free?
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Must excrete Phosphate so that Ca and Phosphate don't bind with each other. Urinary phosphate increases (phosphaturic action)
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Osteoclasts and osteoblasts work together to maintain bone homeostasis, but overtime, osteoclasts are favored. How do we maintain bone homeostasis?
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Give increments of PTH injections. Over time, this favors formation of both osteoclasts and osteoblasts.
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Describe relationship between 1,25(OH)2D3 and PTH
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Can be syngeristic for bone resorption. in absence of vitamin D, PTH isn't as efficient as it would be w/ 1,25(OH)2D3. In absence of PTH, 1,25(OH)2D3 isn't as efficient as it is w/ PTH. BUT very high amts of 1,25(OH)2D3 will turn off PTH.
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What is one way that Rickets and osteomalacia are caused?
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Low Vit D leads to low Ca and low P absorption. Low Ca will trigger increase of PTH which increases bone resorption, and increase Ca. However, increase PTH also decreases phosphate. This decreases bone mineralization and causes these diseases.
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What can hypocalcemia lead to?
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If Pca < 40% normal value, you have this. may be caused by accidental removal of the PT glands.
a. tetany- Trousseau's sign b. low cardiovascular fcn, lower contractility, and lower BP |
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What can hypercalcemia lead to?
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Only if Pca > 14 mg/dl. Increase PTH due to tumor of PT gland (hyperparathyroidism). can lead to bradycardia.
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Name other factors that increase bone formation
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1) estrogen (post-menopause)
2) load bearing exercise 3) bisphosphanates 4) pulsatile PTH 5) insulin 6) statins |
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Name other factors that decrease bone formation
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1) cortisol leads to decrease OPG
2) menopause 3) thyroid hormone |
