CALCIUM

1. CALCIUM FCSFN 648

2. Introduction • Ca is the most abundant mineral in the body • Ca (latin “calx” means limestone) was known as early as the first century when the Ancient Romans prepared lime as calcium oxide

3. Distribution & function in the body - bone • Over 99% Ca exists in the skeleton • Structural role • Functional role • Castatus can be assessed by measuring BMC by bone densitometry

4. Distribution & function in the body - bone • Bone remodeling occurs throughout life • Bone formation is > than resorption during growth (especially adolescence)* in girls - 90% total BMC (17 y) & 99% (26 y)* boys - occurs 18.5 y • In W onset of bone loss occurs * 48 y (spine) & 37 y (femoral neck) • Maximal loss in W occurs * bet 54-58 (hips, spine etc)

5. Distribution & function in the body - bone • On average - bone Ca pool turns over every 5-6 y • 2 types of bones * cortical* trabecular • Cortical bone

6. Distribution & function in the body - bone • Trabecular bone

7. Functions • Mineralization - bone & teeth • Blood clotting

8. Functions • Other functions

9. Solubility • Ca is absorbed only in ionized form (Ca+2) • Ca in food & dietary supplements - insoluble salts • Solubility - mildly acidic pH • Solubility doesn’t ensure better absorption • In alkaline pH, Ca may complex with minerals or other dietary components

10. Calcium location & quantity • Average adult ~ 1 kg Ca (99% - skeleton)as calcium phosphate salts • ECF has ~ 22.5 mmol of which 9 mmol is inthe serum • Every 24 hours, 500 mmol Ca is exchanged bet bone & ECF

11. Normal ranges • Normal serum levels (8.5-10.5 mg/dL) • Normal ionized level (4.5-5.6 mg/dL) • Amount of total calcium is dependent on albumin • Biologic effect of Ca is determined on the amount of ionized Ca rather than the total calcium

12. Corrected Ca level • Corrected Ca level is used when albumin is abnormal • Corrected Ca (mg/dL) = measured total Ca (mg/dL) + 0.8 (4.0 - serum albumin [g/dL]), where 4.0 represents the average albumin level • With hypoalbuminemia corrected level is higher than the total Ca

13. Absorption • Absorption - Ca has to be in the ionized form • Generally 20-50% ingested Ca is absorbed • Amount of Ca absorbed depends • Intake

14. Absorption • Physiological factors

15. Absorption • Occurs along the length of the small intestine • Generally 2 routes of absorption • Other route of absorption

16. Saturable system (Transcellular) • This is active & saturable system (fig) • Takes place mainly in the duodenum & proximal jejunum • Occurs actively when Ca is in short supply (↓ dietary) • Ca moves from brush border into the enterocyte as unbound Ca+2 • Ca+2 binds with intracellular protein (calbindin or CPB) which takes Ca+2 into the mitochondria & other subcell compartments • Ca+2 leaves the enterocyte in exchange for Naor by calcium activated ATPase

17. Saturable system (Transcellular) • Saturable process occurs

19. Passive & Non-saturable (Paracellular) • This is passive & non-saturable system • Takes place mostly jejunum & ileum • Is dependent on vit D • Occurs passively when there is adequate dietary Ca • Ca enters into the enterocyte with the help of vit D

20. Colon • Bacteria in the colon releases Ca bound fermentable fibers • ~ 4% (~ 8 mg/d) of dietary Ca is absorbed by this route • Amount is higher in people who are unable to absorb more Ca from the small intestine

21. Factors that enhance Ca absorption • ↑ lactose • ↑ vit D • ↑ acidic environment • ↓ stress • Distribution of Ca intake • ↑ physiological need

22. Absorption enhanced - lactose • From breast milk & formula • Infants fed lactose • Research - rats fed diets with differentCHOs, i.e. 25%* lactose, glucose, sucrose, maltose or starch* lactose only ↑ Ca absorption (Bergeim et al., 1926)

23. Absorption - enhanced • Vitamin D • Acidic conditions • Lack of stress

24. Absorption - enhanced • Distribution of Ca intake • Increased physiological need

25. Factors that inhibit Ca absorption • Non-fermentable fibers • Phytate • Oxalate • Magnesium • Dietary fatty acids • Physical activity • Potassium

26. Factors that inhibit Ca absorption • Non-fermentable fibers • Phytate • Oxalates

27. Factors that inhibit Ca absorption • Magnesium • Dietary fatty acids

28. Factors that inhibit Ca absorption • PA • Potassium

29. Transport • In the blood, Ca is transported in 3 forms* ~ 40% Ca is bound to protein mainly albumin* ~ 10% is complexed with sulfate, phosphate or citrate* ~ 50% of Ca is found free in blood (ionized Ca+2)

30. Storage • Skeleton is the major storage site* since ~ 99% of the body's Ca is in the bone • Short term • Long term, chronic removal of skeletal calcium

31. Excretion • Primarily in the urine and feces • Urinary losses range from 40-200 mg/d occurs: • Urinary Ca excretion is ↓ • Urinary Ca excretion is ↑

32. Excretion • Most Ca is filtered and reabsorbed by the kidneys

33. Excretion • Fecal losses range from 45-100 mg/d • ↑ fecal losses are ↑ with • Skin losses 60 mg/d

34. Regulation - calcium balance (Extracellulary) • The level of ionized calcium in plasma is controlled by 3 factors:* PTH* Calcitonin* Calcitriol (1,25-(OH)2D3 ) (i.e. vit D)

35. Parathyroid Hormone (PTH) • ↓ in ECF (serum) Ca concentrations • PTH from the PT gland is released • PTH ↑ Ca in the ECF by* ↑ Ca absorption from the intestine (through calbindin)* mobilization of Ca from the bone via stimulation of osteoclasts* ↓ kidney excretion of Ca & ↑ renal tubular reabsorption of Ca

36. Calcitonin • Calcitonin, is synthesized by the thyroid gland • ↑ serum Ca levels stimulates calcitonin • Calcitonin ↓ serum Ca concentration by* inhibiting osteoclast activity* prevents mobilization of Ca from bone

37. Calcitriol (1,25-(OH)2D3 ) • Vit D enters circulation after synthesis inthe skin or consumption in the diet • Vit D is transported through the body bound to a vitamin D-binding protein • Vit D is taken to the liver, undergoes hydroxylation  forms 25(OH)D • 25 (OH)D is bound again to the bindingprotein  kidney where it is furtherhydroxylated  1,25(OH)2D3, the most active vitamin D metabolite

38. Calcitriol (1,25-(OH)2D3 ) • In Ca deficiency, more 1,25 (OH)2D3 is produced causing enhanced* intestinal absorption of Ca* renal reabsorption of Ca* ↑ bone formation & resorption

39. Regulation - calcium balance (Intracellulary) • Calcium Pumps* ATP dependent calcium pumps found* mitochondria * endoplasmic reticulum * nucleus * these enable movement of Ca from extracellular to intracellular fluid

40. Interactions with other nutrients • Phosphorus • Magnesium

41. Interactions with other nutrients • Potassium • Protein

42. Interactions with other nutrients • Sodium • Fiber

43. Interactions with other nutrients • Caffeine

44. Interactions with other nutrients • Alcohol • Sodium & Protein

45. Deficiency - Causes • Inadequate intake • Poor Ca absorption and/or excessive Ca losses • Observed

46. Hypo - & Hypercalcemia • Hypocalcemia • Hypercalcemia • Fatal levels:

47. Deficiency - observed • Disease states • Individuals who have ↑ need

48. Calcium & disease prevention • Osteoporosis • 2 types of osteoporosis

49. Calcium & disease prevention • Type I • Type II

50. Calcium & disease prevention • Hypertension • Cardiovascular Disease • Colon Cancer