Calcium & Vitamin D Physiology

1. Calcium & Vitamin D Physiology Bob Bing-You, MD, MEd, MBA ME Center for Endocrinology Scarborough, Maine

2. Importance of Calcium • Tight physiologic range • Normal function muscle, nerves, PLTs, coagulation factor • Cofactor for enzymes • Membrane stability • So we can stay upright!

6. 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

9. 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

11. 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

12. 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

13. 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

17. Vitamin D deficiency • Osteomalacia [bone without calcium] • Parathyroid glands come to defense at sacrifice of bones • Risk of fractures • Cancer risk?

18. 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

20. 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

21. 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

22. 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

23. Medical conditions • Hypoparathyroidism • Chronic renal failure • Intestinal osteodystrophy [e.g., celiac sprue, gastric bypass]

24. 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

25. 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

26. 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]

27. 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

28. 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

29. Hypocalcemia - signs/sx’s • Paraesthesias • tetany, carpopedal spasm, muscle cramps • Chvostek’s sign • Trousseau’s sign • Prolonged QT • seizures of all types • Laryngospasm, bronchospasm

30. 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

31. Calcium • Carbonate [40% elemental Ca] • Lactate [13%] • Phosphate [25%] • Citrate [17%] • Gluconate best for IV- least irritating

32. 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

33. Causes hypercalcemia • Outpatient- primary hyperparathyroidism • Inpatient - malignancy • Less common • pheochromocytoma • meds: lithium, thiazides, vit D • hyperthyroidism • TB, sarcoid, • critical illness

34. Parathyroid • Needed to facilitate 1,25 hydroxylation • calcium sensing receptor • negative feedback loop • 1-84 amino acids, N-terminal active component

36. 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]

37. Hypercalcemia - signs/sx’s • Lethargy, stupor, coma • mental status changes • N/V, constipation • HTN, short QT, AV block • weakness, bone pain • stones, fractures

38. Hypercalcemia - treatment • Hydration • Furosemide • bisphosphonates [zoledronic acid, pamidronate, etidronate] • calcitonin • steroids for hematologic malignancies • dialysis for renal patients; watch Ca x Phos

39. Take-home points • Calcium balance important for normal physiologic functions • we all need vitamin D! • hypocalcemia life-threatening • hypercalcemia either PHT or malignancy

40. 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