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Calcium & Vitamin D Physiology Bob Bing-You, MD, MEd, MBA ME Center for Endocrinology Scarborough, Maine Importance of Calcium Tight physiologic range Normal function muscle, nerves, PLTs, coagulation factor Cofactor for enzymes Membrane stability So we can stay upright! Calcium balance Net intestinal Ca absorption ~zero when intake <200 mg/d need >400 mg/d to maintain Ca balance >1000 mg/d, intestinal absorption tends to plateau Calcium absorption 1,25-OH vitamin D [calcitriol] only hormonal stimulus for active absorption acts primarily on duodenum, jejunum fairly linear increase in Ca absorption with increasing calcitriol levels The following statement is true: A. You can get enough vitamin D through a window B. Osteoblasts are the “PAC-men meanies” C. 1,25-D is better than 25-D for Ca absorption D. Serum Ca reflects most of our Ca stores History of vitamin D Century-old documents described Vit D disease Rickets in industrial England 1919- rickets produced in dogs fed oatmeal indoors, cured with cod-liver oil 1923- skin precursor identified 1930’s – chemistry determined Normal vitamin D internal production Skin: Vit D3 [cholecalciferol], made by ultraviolet light [can’t get it through windows!] Liver: 25-hydroxy Vit D Kidney: 1,25-dihydroxy Vit D [calcitriol] =active form which acts on intestines – Stimulated by parathyroid hormone Vitamin D deficiency Osteomalacia [bone without calcium] Parathyroid glands come to defense at sacrifice of bones Risk of fractures Cancer risk? How does one get deficient? Winter months [Boston Univ. studies: Nov – Feb] Age related changes: Skin does not convert Vit D3; less intestinal absorption Sun screen Liver or kidney disease How much sunlight do you need? A. None, too dangerous B. One hour a week C. 20 minutes 4 days a week D. One hour a day Dietary sources of vitamin D Egg yolks Fatty fish like salmon Fatty fish oils like cod liver oil Supplemented foods [milk 400IU/Liter, cereals, breads] Typical adult diet <100 IU How do we detect deficiency? 25-hydroxy Vit D level Reflects nutritional stores over months 1,25 Vit D expensive and short-lived normal level, probably > 30 ng/ml This level quiets down parathyroids Medical conditions Hypoparathyroidism Chronic renal failure Intestinal osteodystrophy [e.g., celiac sprue, gastric bypass] Supplements suggested DRI [Dietary Reference Intake]: minimum amount to prevent diseases from deficiency Not for optimal health International Units [40 IU Vit D = 1 microgram] 400 IU?, 800?, 1000? >2000 IU – should be monitored Vitamin D preparations Calcitriol [1,25 vit-D] – Rocaltrol 0.25 to 0.5 mcg per day – Calcijex parenteral 1-2 mcg/ml Calcifediol [25- vit D] – less effective in gut Ca absorption, less hypercalcemia risk Too much is possible! Stays in fat tissue long time Increases calcium loss from bone Premature heart attacks High blood levels, kidney stones Too much sun doesn’t cause Vit D toxicity Watch out for Vitamin A combo [some tablets are cod liver oil, with both A & D] Causes Hypocalcemia Is it truly low? Mental calculation to correct results Ca upwards for low albumin [about 1 to 1] b/c serum total Ca measures bound Ca to albumin – or measure ionized Ca [“free” amount]’ ?reliable test Vitamin D deficiency Hypoparathyroidism – surgery – functional [Mg] Alkalosis Assuming a normal albumin is 4: if your patient has a total Ca reported at 7.0, & with an albumin of 2, what would be the corrected Ca [mentally calculate it]: A. 5.0 B. 7.0 C. 9.0 D. 10.0 E. I need a calculator Hypocalcemia - signs/sx’s Paraesthesias tetany, carpopedal spasm, muscle cramps Chvostek’s sign Trousseau’s sign Prolonged QT seizures of all types Laryngospasm, bronchospasm Hypocalcemia - treatment Any symptomatic patient, or asymptomatic with Ca <7.5 Ca gluconate 10 ml [90 mg] IV in 50 ml D5W or NS, over 5 minutes repeat injections or go with infusion [10 ampules in 1 liter @ 50 ml/hr] start vitamin D if prolonged course expected; replace Mg if necessary Calcium Carbonate [40% elemental Ca] Lactate [13%] Phosphate [25%] Citrate [17%] Gluconate best for IV- least irritating Calcium Carbonate [TUMS]: low cost, antacid properties, highest Ca % Constipation 1000 - 1500 mg/ day achlorhydric pts should take with food IV infusions: watch Ca x Phos product Causes hypercalcemia Outpatient- primary hyperparathyroidism Inpatient - malignancy Less common – – – – – pheochromocytoma meds: lithium, thiazides, vit D hyperthyroidism TB, sarcoid, critical illness Parathyroid Needed to facilitate 1,25 hydroxylation calcium sensing receptor negative feedback loop 1-84 amino acids, N-terminal active component Hyperparathyroidism Secondary - due to low serum Ca Primary - due to single adenoma – Mulitple Endocrine Neoplasia syndrome – surgery: bone loss, kidney stones, serum Ca >11.5 mg% – Medical Rx: receptor blocker [Cinacalcet] Hypercalcemia - signs/sx’s Lethargy, stupor, coma mental status changes N/V, constipation HTN, short QT, AV block weakness, bone pain stones, fractures Hypercalcemia - treatment Hydration Furosemide bisphosphonates [zoledronic acid, pamidronate, etidronate] calcitonin steroids for hematologic malignancies dialysis for renal patients; watch Ca x Phos Take-home points Calcium balance important for normal physiologic functions we all need vitamin D! hypocalcemia life-threatening hypercalcemia either PHT or malignancy Websites www.uwcme.org/courses/bonephy [Dr Susan Ott] www.osteoporosis.ca [Osteoporosis Society of Canada] www.aad.org [Acad of Dermatology] www.vitamin-d.com, www.nutritionfarm.com, www.merck.com