Serum PTH Concentrations in Hypercalcemia and Hypocalcemia Haden

Serum PTH Concentrations in Hypercalcemia and Hypocalcemia Πρωτοπ. Υπερπαρα/σμός ΥπερΑσβεστ. Κακοήθ. /Ακινητοποίηση Υποπαραθυρεοειδισμός Κατά Φύσιν Haden ST et al. Clin Endocrinol 2000; 52: 329

Serum PTH Concentrations in Hypercalcemia and Hypocalcemia Πρωτοπ. Υπερπαρα/σμός ΥπερΑσβεστ. Κακοήθ. /Ακινητοποίηση Υποπαραθυρεοειδισμός Κατά Φύσιν Haden ST et al. Clin Endocrinol 2000; 52: 329

Σχόλια-Παραδείγματα Ca/P i. PTH levels should be low in hypercalcemia due to immobilization. . . Schoenau E, Neu CM, Rauch F, Manz F. The development of …. J Clin Endocrinol Metab 2001; 86: 613 -618. Sato Y. Abnormal bone and calcium metabolism in patients after stroke. Arch Phys Med Rehabil 2000; 81: 117 -121 Bikle DD, Halloran BP. The response of bone to unloading. J Bone Miner Metab 1999; 17: 233 -244 Wang W, Li C, Kwon TH, et al. Reduced expression of renal transporters in rats with hypercalcemia. Am J Physiol 2004; 286: F 534 -F 545

The Exact Mechanisms of Immobilization Hypercalcemia Remain Elusive Loss of mechanical stress (mechanostat critical for bone loss theory) has proven Another proposed mechanism is the acidic environment created by low blood flow that may impair mineralization of bone and increase PTH activity Overall, increased osteoclastic bone resorption and decreased osteoblastic bone formation are hallmarks in bone biopsy. Sato Y , Fujimatsu Y , Kikuyama M , Kaji M , Oizumi K. Influence of. . J Neurol Sci. 1998; 156: 205– 210 Bikle DD, Halloran BP. The response of bone to unloading. J Bone Miner Metab 1999; 17: 233 -244

Σχόλια-Παραδείγματα Vit-D OH HO Vitamin D 3 HO 25 -Hydroxyvitamin D 3 25 (OH)D Αποθηκευτική μορφή OH HO OH 1, 25 -Dihydroxyvitamin D 3 1, 25 (OH)2 D 3 or Calcitriol Ενεργός μορφή

Σχόλια-Παραδείγματα Vit-D 25(OH)D serum levels are accepted as a measure of Vit-D nutritional status… Norman serum levels: 30 -50 ng/ml Στον γενικό πληθυσμό: <20 ng/ml=έλλειψη, <30 ng/ml=ανεπάρκεια (Holick, NEJM, 2007) Shah N, Bernardini J, Piraino B. Prevalence and correction of 25(OH) vita. . . Perit Dial Int 2005; 25: 362– 6 Taskapan H, Ersoy FF, et al. Severe vitamin D deficiency in chro. . . Clin Nephrol 2006; 66: 247– 55

Σχόλια-Παραδείγματα Vit-D Vitamin- D: Levels- Actions Parameter 25(OH)D Total plasma concentration, recommended values 30 to 50 ng/ml 70 to 125 nmol/L 1, 25(OH)2 D 30 to 50 pg/ml 75 to 125 pmol/L Total plasma concentration, Relative levels 1000 1 Binding affinity to vit-D-binding protein Relative levels Half-life 1000 1 Free concentration relative levels VDR affinity, relative values 25 to 30 days 1 1 4 -8 hours 1 500 -1000 Andress DL, Kidney Int. 2006; 69: 33 -43. Brown AJ, et al. Am J Physiol. 1999; 277; 157 -175. Healy KD, et al. Proc Nati Acad Sci USA. 2005; 102: 4724 -4728

Σχόλια-Παραδείγματα Vit-D Vitamin- D: Levels- Actions Parameter Total plasma concentration, recommended values Total plasma concentration, Relative levels Binding affinity to vit-D-binding protein Relative levels Half-life Free concentration relative levels VDR affinity, relative values 25(OH)D 30 to 50 ng/ml 70 to 125 nmol/L 1, 25(OH)2 D 30 to 50 pg/ml 75 to 125 pmol/L 1000 1 25 to 30 days 1 1 4 -8 hours 1 500 -1000 Andress DL, Kidney Int. 2006; 69: 33 -43. Brown AJ, et al. Am J Physiol. 1999; 277; 157 -175. Healy KD, et al. Proc Nati Acad Sci USA. 2005; 102: 4724 -4728

Σχόλια-Παραδείγματα Vit-D Vitamin- D: Levels- Actions Parameter 25(OH)D Total plasma concentration, recommended values Total plasma concentration, Relative levels Binding affinity to vit-D-bind protein Relative levels Half-life Free concentration relative levels VDR affinity, relative values 30 to 50 ng/ml 70 to 125 nmol/L 1000 25 to 30 days 1 1 1, 25(OH)2 D 30 to 50 pg/ml 75 to 125 pmol/L 1 1 4 -8 hours 1 500 -1000 Andress DL, Kidney Int. 2006; 69: 33 -43. Brown AJ, et al. Am J Physiol. 1999; 277; 157 -175. Healy KD, et al. Proc Nati Acad Sci USA. 2005; 102: 4724 -4728

Σχόλια-Παραδείγματα Vit-D Vitamin- D: Levels- Actions Parameter Total plasma concentration, recommended values 25(OH)D 30 to 50 ng/ml 70 to 125 nmol/L 1, 25(OH)2 D 30 to 50 pg/ml 75 to 125 pmol/L Total plasma concentration, Relative levels 1000 1 Binding affinity to vit-D-binding protein Relative levels 1000 1 Half-life Free concentration relative levels VDR affinity, relative values 25 to 30 days 1 1 4 -8 hours 1 500 -1000 Andress DL, Kidney Int. 2006; 69: 33 -43. Brown AJ, et al. Am J Physiol. 1999; 277; 157 -175. Healy KD, et al. Proc Nati Acad Sci USA. 2005; 102: 4724 -4728

Σχόλια-Παραδείγματα Vit-D Vitamin- D: Levels- Actions Parameter Total plasma concentration, recommended values 25(OH)D 30 to 50 ng/ml 70 to 125 nmol/L 1, 25(OH)2 D 30 to 50 pg/ml 75 to 125 pmol/L Total plasma concentration, Relative levels 1000 1 Binding affinity to vit-D-binding protein Relative levels Half-life 1000 1 VDR affinity 25 to 30 days 1 4 -8 hours 500 -1000 Andress DL, Kidney Int. 2006; 69: 33 -43. Brown AJ, et al. Am J Physiol. 1999; 277; 157 -175. Healy KD, et al. Proc Nat Acad Sci USA. 2005; 102: 4724 -4728

Σχόλια-Παραδείγματα Vit-D …. when 25(OH)D is circulating at high levels , it can compete with 1, 25(OH)2 D for binding to VDR and during Vit-D intoxication, 25(OH)D can induce actions that usually are attributed to 1, 25(OH)2 D….

Σχόλια-Παραδείγματα Vit-D Επίπεδα 25 -(OH)D @ Ιστομορφομετρικοί Δείκτες ΧΝΝ-5 σταδίου n: 104 pts Ρυθμός Σχηματισμού Οστικής Μάζας @ Επίπεδα 25(ΟΗ)D …Data are in favor of a direct role of 25(OH)D on bone metabolism in pts with CKD …An defect of 25(OH)D deficiency on bone, consisting of a mineralization and bone formation defect… Coen G et al. 25 -hydroxy-Vit. D…. . Kidney Int, 2005, Oct, 68(4), 1880 -8

Σχόλια-Παραδείγματα Vit-D Vitamin D Levels and Patient Outcome in CKD time to dialysis time to death independent inverse predictor of disease progression and death in pts with CKD… …This study shows that plasma 25 D is an … 25(OH)D was a better predictor of clinical events than 1, 25(OH)2 D… P. Ravani F. Malberti et al: Kidney Int, Jan(1): 75: 2009

Serum PTH Concentrations in Hypercalcemia and Hypocalcemia Πρωτοπ. Υπερπαρα/σμός ΥπερΑσβεστ. Κακοήθ. /Ακινητοποίηση Υποπαραθυρεοειδισμός Κατά Φύσιν Haden ST et al. Clin Endocrinol 2000; 52: 329

Σχόλια-Παραδείγματα Vit-D Extrarenal synthesis of calcitriol [1, 25(OH)2 D 3] is central to the pathogenesis of abnormal calcium homeostasis , in carcoidosis But alterations in parathyroid hormone (PTH) activity and the expression of PTH‐related peptide have also been demonstrated. hypercalcaemia hypercalcuria reduced bone density (5 – 10%), (40– 62%) (40– 55%

Σχόλια-Παραδείγματα Vit-D In 1983 the extrarenal source of calcitriol in sarcoidosis was shown to be the alveolar macrophage, which contained the 1‐α hydroxylase enzyme and produced calcitriol when cultured in vitro Additional work has shown that tissue macrophages at other sites also produce calcitriol Adams JS, Sharma OP, Gacad MA et al. J Invest Med 1983; 72: 1856– 60 Adams JS, Singer FR, Gacad MA et al. J Clin Endocrinol Metab 1985; 60: 960– 5 Mason RS, Frankel T, Chan YL et al. Ann Intern Med 1984; 100: 59– 64

Σχόλια-Παραδείγματα Vit-D …. in alveolar macrophages there is no downregulation of 1 a-hydroxylase in response to high levels of calcitriol and the up-regulation of 25(OH)D 324 -hydroxylase requires much higher levels of 25(OH)D…

Σχόλια-Παραδείγματα Vit-D …calcitriol has been shown to down-regulate the activation and proliferation of lymphocytes, probably through the inhibition of interleukin-2 (IL-2) and interferon-γ (INFγ)… …calcitriol-mediated inhibition of INFγ and IL-2 is an attempt by the body to down-regulate T-cell activity at sites of inflammation…