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Calcium
misc.
| Question | Answer |
|---|---|
| Vitamin D enhances transcription of: | Epitheilial Ca entry Channel (ECaC), several Ca binding proteins, basolateral Ca-ATPase (final extrusion of Ca into the plasma) |
| Thiazide Diuretics | Encourage the reabsorption of Ca in kidney |
| Osteoclast origin | Bone marrow stem cells, related to monocytes and macrophages |
| Biochemical estimates of Bone resorption in Urine | Hydroxyproline and Hydroxydeoxy pyridinoline |
| Osteoblast Origin | Mesenchymal stem cells related to fibroblasts, cartilage, muscle, and fat |
| Osteoblastic functions | Forms bone; stimulates bone resorption (factor M-CSF, cytokines IL-1, 6, 11 >>> OPGL, obligatory for osteoclastic differentiation) |
| Regulation of M-CSF | (+) IL-1 and TNF alpha; (-) Estrogen |
| OPGL to OPG stimulated by | elevated PTH, excess 1, 25 OH and IL-11 |
| Alkaline phosphatase | Marker enzyme for Osteoblasts |
| What inhibits osteoclastic activity | TGF-beta, bone sialoprotein II, Ca |
| Osteopontin, Osteocalcin, Bone sialoproteins | chemotactic factors for osteoblasts |
| Resorption driven by PTH stimulates what? | production of IGF-1 for osteoblastic growth |
| Parathyroid Hormone chemistry | 84 aa. Biological activity resides in N terminal portion. MINUTE TO MINUTE regulation of ionized calcium |
| The hypercalcemic hormone | PTH |
| PTH and PO4 | inhibits tubular reabsorption of phosphate, increased urinary secretion of PO4 |
| PTH increases Vitamin D production where? | Proximal tubule |
| PO4 reabsorption in kidney resulting from PTH action | reduced PO4 absorption in PT (Na-P cotransporter is inhibited) |
| Calcium reabsorption in kidney resulting from PTH action | PT: reduced reabsorption, inhibited Na-H exchanger. Enhanced reabsorption in the DT( ECaC) and TAL (paracellular) |
| How does PTH increase absoprtion of Ca and PO4 in intestine | Indirectly by increasing Vit. D |
| PTH and Bone resorption | Indirectly increases bone resortion by stimulating osteoblasts to produce MCSF and OPGL |
| Elevated levels of PTH and Bone formation | Elevated levels of PTH directly inhibit osteoblatic activity. paradox: PTH increases IGF-1 a growth factor for Osteoblasts |
| Low levels of PTH and bone formation | enhance bone remodeling and induce net increase in bone formation |
| PTH mechanism of action | G protein, adenylate cyclase, phospholipase C |
| What inhibits transcription of PTH? | elevated Ca and Vit. D |
| What elevates transcription of PTH? | elevated PO4 |
| PTH preps | Teriparatide: rhPTH |
| Use of PTH drugs | promote bone growth, halt osteoporosis, distinguish between pseudohypoparathyroidism (unresponsive to drug) and hypoparathyroidism |
| Cholecalciferol | Vitamin D3. Formed from UV light |
| Ergocalciferol | Vitamin D2. dietary supplements |
| Calcifediol | 25 OH D3. Formed in liver. GOOD INDICATOR OF VIT D STATUS IN PERSON. Main Vit.D compound in plasma. Half life is 2 wks |
| Calcitriol | 1, 25 (OH)2 D3. Formed by 1 alpha hydroxylase in renal mitochondrial. Most potent metabolite of Vit. D. |
| 1 alpha hydroxylase | Forms Calcitriol in Kidney |
| What catabolizes Vit.D | 24 Hydroxylase. Ubiquitely expressed in Vit. D target tisses. Initial step in hormone break down |
| Function of Vit D | Raise serum Ca and PO4. day to day balance of Ca. |
| Vitamin D and intestine | Increases absoprtion of Ca and PO4. Enhanced production of ECaC in lumen, more calcium binding proteins, more Ca ATPase in seroso (basolatoral surface).. Increases expression of Na-P cotransporter |
| Vitamin D and kidney | incraeses reabsorption of Ca and PO4. Increases Ca reabsorption in DT and CCT via more ECaC. More Na-P transproters. Suppression of 1 alpha hydroxylase. Stimulates 24 hydroxylase activity |
| Vitamin D and Bone | promotes bone turnover. Deposition of bone (supersaturating levels of PO4 Ca). Osteoclast recruitment, differentiation. Osteoblasts: inhibited proliferation, promotes differentiation |
| Vitamin D and Chief Cells of Parathyroid gland | Reduces PTH synthesis and secretion and suppresses gland growth |
| Vitamin D and parafollicular cell of thyroid | reduces calcitonin secretion |
| Vitamin D and effect on its own receptor | Transcriptionally upregulates own receptor. |
| Vit. D transcriptional upreg of own receptor: clinical use | use of Vit D in early stages of renal failure to prevent resistance; prevents 2ndary hyperparathyroidism |
| Vitamin D receptors (VDR) | high affinity receptor acting as ligand activated transcription factor |
| Contraol of 1,25 (oh)2D3 biosynthesis | genomic Control: 1 alpha hydroxylase gene stimulated by PTH and estrogen and low PO4 |
| Ectopic Vit D production | granulomatous conditions (sarcoidosis, tuberculosis, disseminated candidiasis, silicon-indyced granuloma, lymphoma |
| Metabolic Rickets | Renal deficit/phosphate leak, intestinal absorption deficit |
| Renal Deficit/phosphate leak (cause of rickets) Etiology | Hypophosphatemic rickets. Inherited, mostly x linked. Failure to reabsorb PO4. Modest benefit and high doses of 1,25 (OH)2 D3 and phosphate salts |
| Vitamin D dependent rickets | Intestinal absoption deficit. Inherited deficiency of 1 alpha hydroxylase |
| Hypoparathyroidism and Pseudohypoparathyroidism | Low Ca, high PO4 |
| Hypoparathyroidism and Pseudohypoparathyroidism (treatment) | D3 compund; DHT (D2 compound) cts rapildy, not as potent; 1 alpha OH Vit D, no need for renal hydroxylation |
| Renal osteodystrophy (description) | RENAL FAILURE>>leads to high PO4, impaired synthesis of Vit D 3, development of secondary hyperparathyriodism |
| Renal osteodystrophy effects on BONE | osteitis fibrosa, osteomalacia |
| Renal osteodystrophy (treatment) | reduce PTH levels, replace defience calcitriol, DHT and 1 alpha OHD3 effective |
| 19 Nor 1,25 ()H)2D3 | parathyriod suppressor without calcemic actions |
| Psoriasis | keratinocytes proliferate, do not function normally, Vit. D suppresses proliferation. |
| Vitamin D excess (side effects) | Hypersensitiivity (upreg of Vit D receptor); Hypercalcemia; Dhydration (inhibitition of ADH); Cessation of Growth; feus with congenital aortic stenosis; newborn with low PTH, tentany, convulsions |
| Bisphosphanates (general) | Analogs of Pyrophosphate, not metabolized, very long half life in vivo |
| Bisphosphanates (preps) | Etidronate, Pamidronate, Alendronate, Risendronate |
| First Generation Bisphosphonate | Etindronate; Binds strongly to bone mineral,hydrosyapatite. Released when bone resorbed. inhibits dissolution of hydroxyapatite; reduces bone formation |
| Second/third Generation Bisphosphonate (general) | Amino Bisphoshonates are more potent. Action via osteoclast inhibition. Reduce bone resorption without direct effect on bone formation. |
| Pamidronate | Less effect on bone |
| Alendronate, Risendronate mode of administration | Oral |
| Paget's Disease Etiology | slow viral infection |
| Pagets Disease phyiology | Rapid bone turnover, dense bone that is not structurally sound |
| paget's Disease treatment | Bisphosphonates given orally in six month course |
| Humural Hypercalcemia of malingnancy | Induced overproduction of PTH-like protein parathyroid homone related peptide. this protein normally in skin keratinoytes. PTH receptor activated by the protein. PO4 NOT ELEVATED. GFR reduced by elevated Ca. |
| Humural Hypercalcemia of malingnancy (treatment) | Bisphosphnates. Pamindronate infusions last much longer |
| Osteoporosis | Aledronate increases bone mineral density of lumbar spine, femoral neck, trochanter |
| Bisphosphnate toxicities (1st generation) | First generation: sops bone mineralizationand mineral dissoultion, inhibition of bone formation with chronic use (use intermittently) |
| Bisphosphnate toxicities (2nd generation) | Oral agents poorly aborbed. local irritation in upper GI tract. Contraindicate in peope with GI disorders, renal insufficiency. Correct hypcalcemia b4 therapy |
| Calcitonin function | Decreases PO4 and Ca. directly suppresesses osteoclastic acivitity. with continued use, bone formation also reduced. |
| Calcitonin physiology | Delays Ca absorption in intestine, increases urinary excretion of Ca (DT, CCT); and PO4 (PT) |
| Control of calcitonin secretion | Calcium stimulates calcitonin secretion; transcription inhibited by VitD3, stimulated by cAMP/glucocorticoids |
| Agents that raise cAMP have what effect on calcitonin secretion? | Raise calcitonin secretion |
| Calcitonin Preps | recombinant salmon calcitonin, human calctonin, intranasal formulation |
| Therapeutic uses of calcitonin | Paget's Disease, emergency treatment of hypercalcemia, postmenopausal osteoporosis (calcitonin plus calcium) |
| Use of calcium/estrogen/PTH plus vitamin D | osteoporosis |
| Bisphosphonates/furosemide/EDTA | Hypercacemia, Paget's, Osteoporosis |
| Cacitonin used for: | Paget's Disease of bone, Osteoporosis, Hypercacemia of pregnancy |
| PTH therapy for: | Osteoporosis, Diagnositc pseduohypoparathyroidism |
| Vitamin D and metabolites used for: | Rickets, osteomalacia, hypocalcemia, hypoparathyroidism, Vit D resistant rickets, X linked hypophosphatemia |
Created by:
Adetoun
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