1. C ALCIUM METABOLISM DISORDERS

2. O VERVIEW : Calcium definition and requirement. Calcium metabolism regulators : VD, PTH and calcitonin. Functions of calcium. Calcium metabolic bone diseases. Calcium metabolism disorders. CASE !!

3. W HAT IS CALCIUM ? Calcium is a mineral that is essential to bone health, cardiovascular health, muscle maintenance, circulatory health, and blood clotting. Calcium also acts as an enzyme activator. While calcium is found in milk and dairy products, it is also available from other food sources, such as green leafy vegetables, seafood (eating salmon with the bones provides an even greater dose), almonds, blackstrap molasses, broccoli, enriched soy and rice milk products, figs, soybeans and tofu.

4. B ODY REQUIREMENTS Age (in years) Calcium Requirement 1 – 3 500mg 4 - 8 800mg 9 - 18 1300mg 19 - 50 1000mg 51+ 1500mg *Pregnant and lactating women are recommended a daily calcium intake of 1000mg.

5. D IFFERENT F ORMS OF C ALCIUM At any one time, most of the calcium in the body exists as the mineral hydroxyapatite, Ca 10 (PO 4 ) 6 (OH) 2. Calcium in the plasma: 45% in ionized form (the physiologically active form) 45% bound to proteins (predominantly albumin) 10% complexed with anions (citrate, sulfate, phosphate) To estimate the physiologic levels of ionized calcium in states of hypoalbuminemia: [Ca +2 ] Corrected = [Ca +2 ] Measured + [ 0.8 (4 – Albumin) ]

6. R EGULATING FACTORS It is regulated by : PTH and 1,25-(OH)2D3 on gut, kidney and bone Calcium receptors: are present in the parathyroid gland, kidney, brain and other organs.

7. V ITAMIN D METABOLISM The active form of vitamin D is 1,25- dihydroxycholecalcififerol. Its production in the kidney is catalyzed by 1 a-hydroxylase. 1 a-hydroxylase activity is increased by : Decreased serum Ca2+ Increased PTH level Decreased serum phosphate

8. A CTION OF 1,25- DIHYDROXYCHOLECALCIFIFEROL (C ALCITRIOL ) Increases intestinal Ca2+ absorption Increases intestinal phosphate absorption Increase renal reabsorption of Ca2+ and phosphate Increases resorption of bone

9. P ARATHYROID HORMONE (PTH): it is an 84-amino-acid hormone. Secretion: from the chief cells of the parathyroid glands. Function: increase renal phosphate excretion, and increases plasma calcium by: Increasing osteoclastic resorption of bone (occurring rapidly). Increasing intestinal absorption of calcium (a slower response). Increasing synthesis of 1,25-(OH)2D3 (stimulating GIT absorption). Increasing renal tubular reabsorption of calcium

10. R EGULATION OF PTH Low serum [Ca +2 ]  Increased PTH secretion High serum [Ca +2 ]  Decreased PTH secretion

11. C ALCITONIN Produced by : thyroid C cell. Function: Inhibition of osteoclastic bone resorption. Increasing the renal execration of calcium and phosphate. Stimulant ??

13. I NHIBITING FACTORS The amount of calcium consumed at one time can also affect absorption. In other words, calcium absorption decreases as the amount of calcium consumption increases in a meal. Thus, spreading consumption of calcium throughout your day is best. Age

14. C ONT, Fiber, particularly from wheat bran, could also prevent calcium absorption because of its content of phytate dietary sodium and protein increase calcium excretion as the amount of their intake is increased Caffeine has a small effect on calcium absorption. It can temporarily increase calcium excretion and may modestly decrease calcium absorption,

15. F UNCTIONS Muscle contraction Signal transmission Body structure

16. D EFICIENCY : Deficiency of calcium levels in the body may induce several diseases: Rickets disease Adult osteomalacia osteoporosis

17. Rickets : is a softening of bones in children potentially leading to fractures and deformity. The predominant cause is a vitamin D deficiency, lack calcium in the diet may also leads to rickets Osteomalacia : is the softening of the bones due to defective bone mineralization It may show signs as diffuse body pains, fragility of the bones. A common cause of the disease is deficiency in vitamin D, which is normally obtained from the diet and/or sunlight exposure

18. Osteoporosis a disease characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased risk of fractures of the hip spine, and wrist, leading to bone fragility. Men as well as women are affected by osteoporosis. women had high rate to be affected by osteoporosis

20. C ALCIUM METABOLISM DISORDERS : Calcium metabolism disorder include: Hypercalcemia Hypocalcemia hyperparathyrodism

21. HYPERCALCEMIA Is condition in which the calcium level in the body is above the normal. The need of the calcium for the bone formation and muscle contraction, releasing hormone. The main cause is over activity of the parathyroid gland. cancer and some medication may cause over activity of the calcium level.

22. E TIOLOGY OF HYPERCALCEMIA Increased GI Absorption: Vitamin D excess Elevated PTH Decreased Urinary Excretion: Thiazide diuretics Increased Loss From Bone: Elevated PTH Hyperparathyroidism Malignancy Osteolytic metastases

23. C OMPLICATION : Metastatic calcification Renal stones

24. HYPOCALCAEMIA Is a condition in which the calcium level below The normal level Is caused by low level of PTH, low level of magnesium, deficiency of vitamin D The kidney dysfunction play role in hypocalcuimia

25. E TIOLOGY OF THE HYPOCALCEMIA Decreased GI Absorption Poor dietary intake of calcium,impair absorption Increased Urinary Excretion Decreased Bone Resorption/Increased Mineralization Low PTH PTH resistance Vitamin D deficiency,

26. C OMPLICATION. Tetany: condition of mineral imbalance in the body that results in severe muscle spasms. usually occurs when the concentration of calcium ions (Ca++) in extracellular fluids below normalmuscle spasm calcium

27. H YPERPARATHYROIDISM. Hyperparathyroidism occur in two major forms: Primary: most common cause of hypercalceimia.it represents autonomous production of PTH. Secondary:is caused by any chroinc condition assocaited with chroinc depression in the calcuim level. Tertiary hyperparathyroidism: rarely occur

28. C ASE 1 a 59 year old woman with a past medical history significant for hypertension who comes for a routine clinic visit. She initially states that she has no symptomatic complaints, but later in the interview describes chronic fatigue and a mildly depressed mood. Her exam is unremarkable. She used thiazide diuretics as treatment for hypertension, Labs results showed: Calcium (total) – 11.9 mg/dL (normal ~ 8.5-10.2 mg/dL) Phosphate – 1.8 mg/dL (normal ~ 2.0-4.3 mg/dL) Albumin – 3.8 g/dL (normal ~ 3.5-5.0 g/dL) PTH – 124 pg/mL (normal ~ 10-60 pg/mL) Creatinine – 1.2 mg/dL

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