Calcium Metabolism.pptx

Calcium absorption, Calcium excretion, biochemical functions of calcium, calcium homeostasis

1. Calcium metabolism Seminar presentation PRESENTED BY Somya Jain PG 1 st year RCDS & RC,Bhopal

2. Contents Introduction Sources of calcium Body distribution of calcium Calcium absorption Excretion of calcium Biochemical functions of calcium Calcium homeostasis Clinical importance Conclusion 2

3. Introduction Nutrients  are the nutritious components in foods that an organism utilizes to survive and grow.  Classified as – 3 1. Macronutrients 2. Micronutrients Carbohydrates Fats Protein Water Vitamins Minerals Biochemistry by U Satyanarayana & U. Chakrapani 3rd edition

4. What are Minerals??? Inorganic elements that constitute only a small proportion of the body wt. Perform several vital functions absolutely essential for the existence of organism. Wide variation in their body wt. distribution. 4 Biochemistry by U Satyanarayana & U. Chakrapani 3rd edition

5. Classification of Minerals 5 Biochemistry by U Satyanarayana & U. Chakrapani 3rd edition

6. Principal Elements 6 Biochemistry by U Satyanarayana & U. Chakrapani 3rd edition

7. Trace Elements 7 ESSENTIAL POSSIBLY ESSENTIAL NON ESSENTIAL Biochemistry by U Satyanarayana & U. Chakrapani 3rd edition

8. Sources of Calcium Most abundant among the minerals in body. 8 http://ods.od.nih.gov/factsheets/Calcium-HealthProfessional /- national institute of health office of dietary supplements ; cimsasia.com

9. Recommended dietary allowances for calcium (FNB) Age Male Female Pregnant Lactating 0-6 months 200mg 200 mg 7-12 months 260mg 260mg 1-3 years 700mg 700mg 4-8 years 1000mg 1000mg 9-13 years 1300 mg 1300mg 14-18 years 1300mg 1300mg 1300mg 1300mg 19-50 years 1000mg 1000 mg 1000mg 1000 mg 51-70 years 1000 mg 1200 mg 71+ years 1200 mg 1200 mg 9 Recommended Dietary Allowance (RDA): average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals http://ods.od.nih.gov/factsheets/Calcium-HealthProfessional /- national institute of health office of dietary supplements

10. Distribution of Calcium Body of a young adult human contains abt. 1100 gms (27.5 mol) of calcium. 99% of Ca is in skeleton. 10 Guyton textbook of medical physiology – 11th edition

11. Overview of Ca in ECF Normal value of ECF = 9.4mg/dl (2.4mmol Ca/ lt ) ECF conc. – regulated very precisely. An important feature of extracellular calcium regulation is that only about 0.1 % of the total body calcium is in the ECF, about 1 % is in the cells, and the rest is stored in bones. Therefore, the bones can serve as large reservoirs, releasing calcium when ECF concentration decreases and storing excess calcium. 11 Guyton textbook of medical physiology – 11th edition

12. Overview of Ca in plasma & ICF 12 Guyton textbook of medical physiology – 11th edition

13. Absorption of Calcium Abt. 40% of avg. daily dietary intake of Ca is absorbed from the gut. Mainly from the duodenum & first half of the jejunum. Absorption occurs against electrical & conc. gradients. Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition 13

14. Mechanism of absorption 2 mechanisms have been proposed- Simple diffusion An “active” transport process involving energy & Ca²⁺ pump. Both the processes require 1,25 dihydroxycholecalciferol & also Ca²⁺ dependent ATPase . 14 Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

15. Factors affecting absorption pH of intestinal milieu – Acidic pH – favors absorption – soluble Ca salts formed . Alkaline medium – lowers absorption – formation of insoluble tricalcium phosphate. 15 Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

16. 2. Composition of diet – 16 Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

17. 3. State of health of indivual & aging – Healthy adult : absorbs 40% of dietary Ca. >60 yrs : gradual decline in intestinal absorption. 4. Hormonal – Parathhormone – favors absorption Calcitonin & glucocorticoids – lowers absorption. 17 Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

18. Distribution of Calcium Fundamentals of biochem – Dr. A.C.Deb 7th edition 18

19. Excretion of Calcium Excreted in urine, bile & digestive secretions. Unabsorbed Ca – excreted as fecal calcium. 70-90% of Ca eliminated from body – excreted in feces. Small amt. – excreted into intestines after absorption. Daily loss of Ca in sweat is abt.- 15% 19 Fundamentals of biochem – Dr. A.C.Deb 7th edition

20. Renal threshold for serum Ca – 10mg/dl Ingestion of excess proteins Increases acidity Increased Ca excretion in urine Excretion of Ca into feces- increased in Vit.D deficiency. 20 Biochemistry by U Satyanarayana & U. Chakrapani 3rd edition

21. 21 Overview of calcium exchange between different tissue compartments in a person ingesting 1000 mg of calcium per day. Guyton textbook of medical physiology – 11th edition

22. Biochemical functions of Calcium Calcification of bones & teeth – Formation of hydroxyapatite & physical strength of skeletal tissue. Continuous process. Bones in dynamic state acts as a reservoir of Ca. 22 Biochemistry by U Satyanarayana & U. Chakrapani 3rd edition

23. 2. Muscle contraction 3. Nerve transmission 4.Blood coagulation 5. Membrane integrity & permeability 6. Enzyme activation 7.Calmodulin activated action of Ca²⁺ 23 Biochemistry by U Satyanarayana & U. Chakrapani 3rd edition

24. 8. Intracellular messenger 9. Hormonal release 10. Secretory process 11. Contact inhibition 12. Myocardial action 13. Neurotransmitter release 14. Role in mitotic division 24 Biochemistry by U Satyanarayana & U. Chakrapani 3rd edition

25. Calcium Homeostasis Blood Ca is tightly regulated by – Principle organ systems – Intestine Bone Kidney 2. Hormones – Parathyroid hormone Vit . D Calcitonin 25 Guyton textbook of medical physiology – 11th edition

26. CALCIUM HOMEOSTASIS DIETARY CALCIUM INTESTINAL ABSORPTION DIETARY HABITS, SUPPLEMENTS BLOOD CALCIUM BONE KIDNEYS URINE & FAECES THE ONLY “IN” THE PRINCIPLE “OUT” Balance should exists between “IN” & “OUT” factors Guyton textbook of medical physiology – 11th edition

27. Hormonal Control of Calcium Metabolism Hormones involved – 1,25 dihydrocholecalciferol Parathyroid hormone Calcitonin Parathyroid hormone related protein Miscellaneous hormones – Glucocorticoids Growth hormone Estrogen Thyroid hormone Insulin 27 Guyton textbook of medical physiology – 11th edition

28. VITAMIN D 28 Sources of Vit.D – Synthesized by the body on its own. Dietary sources – milk & multiple vitamins. Guyton textbook of medical physiology – 11th edition

29. SYNTHESIS SKIN LIVER KIDNEY 7- DEHYDROCHOLESTEROL VITAMIN D 3 VITAMIN D 3 25(OH)VITAMIN D UV rays 25-HYDROXYLASE 25(OH)VITAMIN D 1,25(OH) 2 VITAMIN D ( ACTIVE METABOLITE ) 1 a -HYDROXYLASE Best screening test for Vit.D adequacy Mediates tissue specific Vit.D responses Guyton textbook of medical physiology – 11th edition

30. Mechanism of action 1,25 dihydroxycholecalciferol (steroid compound) Acts via steroid receptor superfamily Exposes the DNA binding domain & result in increased transcription of some mRNA’s 30 Guyton textbook of medical physiology – 11th edition

31. Actions of Vitamin D “Hormonal” Effect of Vitamin D to Promote Intestinal Calcium Absorption 1,25-Dihydroxycholecalciferol itself functions as a type of “hormone” to promote intestinal absorption of calcium. 31 Guyton textbook of medical physiology – 11th edition

32. It does this principally by – Increasing, over a period of about 2 days, formation of a calcium-binding protein in the intestinal epithelial cells. (brush border) Calcium then moves through the basolateral membrane of the cell by facilitated diffusion into cell cytoplasm. 32 Guyton textbook of medical physiology – 11th edition

33. Rate of calcium absorption is directly proportional to the quantity of this calcium-binding protein. Protein remains in the cells for several weeks after the Vit.D has been removed from the body, thus causing a prolonged effect on calcium absorption. 33 Guyton textbook of medical physiology – 11th edition

34. Other effects of Vit.D that might play a role in promoting calcium absorption are the formation of - a calcium-stimulated ATPase in the brush border of the epithelial cells (2) an alkaline phosphatase in the epithelial cells. 34

35. 35 Guyton textbook of medical physiology – 11th edition

36. 2. Promotes Phosphate Absorption by the Intestines. 3. Decreases Renal Calcium and Phosphate Excretion Vitamin D also increases calcium and phosphate absorption by the epithelial cells of the renal tubules. Thus, decrease excretion of these substances in the urine. 36 Guyton textbook of medical physiology – 11th edition

37. 4 . Effect of Vitamin D on Bone and Its Relation to Parathyroid Hormone Activity extreme quantities of vitamin D causes absorption of bone . In absence of Vit.D , the effect of PTH in causing bone absorption is greatly reduced or even prevented. Vitamin D in smaller quantities promotes bone calcification . 37 Guyton textbook of medical physiology – 11th edition

38. Parathyroid Hormone Parathyroid gland – 4 in no. located immediately behind the thyroid gland. 6*3*2 mm 2 types of cells- Chief cells oxyphil cells 38 Secrete PTH Modified or depleted chief cells that no longer secrete hormone. Guyton textbook of medical physiology – 11th edition

39. Chemistry of PTH – Preprohormone ( ribosomes )(110 A.A’s) Prohormone (90 A.A’s) Hormone (ER & GA ) (84 A.A’s) Mol. Wt. – 9500 Normal plasma PTH level – 10-55pg/ml Half life – 10 mins 39 Guyton textbook of medical physiology – 11th edition

40. Actions of PTH Increases Calcium and Phosphate Absorption from the Bone 2 PHASES – Rapid phase – Begins in minutes and increases progressively for several hours. This phase results from activation of the already existing bone cells (mainly the osteocytes ) to promote calcium and phosphate absorption. 40 Guyton textbook of medical physiology – 11th edition

41. b. Slow phase – Requires several days or even weeks to become fully developed. It results from proliferation of the osteoclasts , followed by greatly increased osteoclastic reabsorption of the bone itself. 41 Guyton textbook of medical physiology – 11th edition

42. 2. Decreases Calcium Excretion and Increases Phosphate Excretion by the Kidneys increases calcium absorption occurs mainly in the late distal tubules, the collecting tubules, the early collecting ducts, and possibly the ascending loop of Henle to a lesser extent. diminishes phosphate reabsorption . 42 Guyton textbook of medical physiology – 11th edition

43. 3. Increases Intestinal Absorption of Calcium and Phosphate PTH greatly enhances both calcium and phosphate absorption from the intestines by increasing the formation of 1,25-dihydroxycholecalciferol in the kidneys. 43 Guyton textbook of medical physiology – 11th edition

44. Control of Parathyroid Secretion by Calcium Ion Concentration Slight decrease in calcium ion concentration in the ECF increase the rate of secretion of the parathyroid glands within minutes. Eg . In conditions like – Rickets Pregnancy Lactation 44 Guyton textbook of medical physiology – 11th edition

45. Conversely, conditions that increase the calcium ion concentration above normal cause decreased activity and reduced size of the parathyroid glands. Such conditions include (1) excess quantities of calcium in the diet (2) increased vitamin D in the diet (3) bone absorption caused by factors other than PTH 45 Guyton textbook of medical physiology – 11th edition

46. Calcitonin Peptide hormone secreted by the thyroid gland. 32-amino acid peptide with a molecular weight of about 3400. Synthesis and secretion of calcitonin occur in the parafollicular cells, or C cells. Increased Plasma Calcium Concentration Stimulates Calcitonin Secretion. 46 Guyton textbook of medical physiology – 11th edition

47. Actions of Calcitonin Decreases Plasma Calcium Concentration Two ways- 1. The immediate effect is to decrease the absorptive activities of the osteoclasts and possibly the osteolytic effect of the osteocytic membrane throughout the bone, thus shifting the balance in favor of deposition of calcium in the exchangeable bone calcium salts. 47 Guyton textbook of medical physiology – 11th edition

48. 2. more prolonged effect of calcitonin is to decrease the formation of new osteoclasts Reduced osteoclastic and osteoblastic activity and, consequently, very little but prolonged effect on plasma calcium ion concentration. 48 Guyton textbook of medical physiology – 11th edition

49. Other Hormones Parathyroid hormone related protein ( PTHrP ) Produced by different tissues of our body Binds to PTH receptors Marked effect on growth and development of cartilage in utero . Defect in PTHrP – severe skeletal deformities. 49 Guyton textbook of medical physiology – 11th edition

50. 2. GLUCOCORTICOIDS Inhibit protein synthesis in osteoblasts , thereby decreases synthesis of organic matrix of bone. Inhibit absorption of Ca and Po 4 from the gut and facilitate its excretion in the kidneys lowers plasma calcium level. 50 Guyton textbook of medical physiology – 11th edition

51. 3. Growth Hormone Increases intestinal absorption of Calcium “Positive calcium balance” 4. Thyroid Hormone Hypercalcemia , Hypercalciuria and Osteoporosis . 5. Estrogens Prevents osteoporosis by inhibiting certain cytokines 6. Insulin Increases bone formation 51 Guyton textbook of medical physiology – 11th edition

52. Clinical Importance Hypercalcemia – When serum Ca levels exceeds 11.0mg/dl. 52 Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

53. Causes : A)Primary hyperparathyroidism May be due to – i ) Familial ii) Hyperplasia of chief cells-15% case iii) Tumors – Solitary adenoma – 80-85% cases Multiple adenomas – 2% cases Parathyroid carcinoma - <1% cases 53 Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

54. Extreme osteoclastic activity in the bones. inc. Ca ion & dec . P ion conc in ECF Tendency to form kidney stones. calcium phosphate & calcium oxalate High level of plasma alkaline phosphatase – diagnostic feature . 54 Guyton textbook of medical physiology – 11th edition

55. Cause the plasma calcium level to rise to 12 to 15 mg/dl and, rarely, even higher. depression of the CNS & PNS, muscle weakness, constipation, abdominal pain, peptic ulcer, lack of appetite, and depressed relaxation of the heart during diastole. 55 Guyton textbook of medical physiology – 11th edition

56. Radiographs of the bone show extensive decalcification and, occasionally, large punched-out cystic areas of the bone that are filled with osteoclasts in the form of so-called giant cell osteoclast “tumors.” The cystic bone disease of hyperparathyroidism is called osteitis fibrosa cystica . 56 Guyton textbook of medical physiology – 11th edition

57. B) Malignancy – Humoral factors – like PTHrP , TGF, EGF,PDGF Direct skeletal involvement by the tumors Hematological malignancies. C) Other endocrine causes – Hyper & hypothyroidism Acromegaly Acute adrenal insufficiency 57 Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

58. D) Granulamatous diseases – TB Sarcoidosis Berylliosis E) Overdosage of vitamins – Vit.A intoxication Hypervitaminosis D 58 Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

59. F) Drug induced – Thiazide diuretics Spironolactone Milk alkali syndrome G) Miscellaneous causes- Idiopathic hypercalcemia of infancy – Williams syndrome Hyperalbuminemia & hyperglobulinemia Renal failure 59 Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

60. 2 . Hypocalcemia When serum Ca is less than 8.5mg/dl. 60 Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

61. Causes – Hypoalbuminemia Commonest cause May be due to- malnutrition Nephrotic syndrome Chronic liver ds . B) Hypoparathyroidism May be – surgical induced – 90% cases Idiopathic Bio inactive PTH 61 Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

62. C) Renal diseases & Renal failure D) Pseudohypoparathyroidism – PTH is normal Defect is in PTH receptors E) Hypoaparathyroidism in association with other diseases – Addison’s ds Pernicious anemia Candidiasis 62 Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

63. F) Miscellaneous causes – Acute pancreatitis Medullary carcinoma of thyroid Magnesium deficiency Iatrogenic – administration of drug Foscarnate in AIDS pts. Neonatal hypocalcemia - due to prematurity Vit.D deficiency or resistance – Rickets & Osteomalacia 63 Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition

64. Vitamin D deficiency Rickets occurs mainly in children. results from calcium or phosphate deficiency in the ECF, usually caused by lack of vitamin D. Plasma calcium concentration in rickets is only slightly depressed, but the level of phosphate is greatly depressed. 64 Guyton textbook of medical physiology – 11th edition

65. During prolonged rickets marked compensatory increase in PTH secretion causes extreme osteoclastic absorption of the bone bone becomes progressively weaker and imposes marked physical stress on the bone 65 Guyton textbook of medical physiology – 11th edition

66. In the early stages of rickets, tetany almost never occurs. However, when the bones finally become exhausted of calcium, the level of calcium may fall rapidly. As the blood level of calcium falls below 7 mg/dl, the usual signs of tetany develop. 66 Guyton textbook of medical physiology – 11th edition

67. Treatment – supplying adequate calcium and phosphate in the diet. administering large amounts of vitamin D. 67 Guyton textbook of medical physiology – 11th edition

68. Tetany Occurs in patients with low levels of calcium . Intermittent spasm of the peripheral muscles due to increased excitability of peripheral nerve. Textbook of medicine – khosla 6th edition 68

69. Trousseau sign –contraction of distal muscles of the hands (carpal spasm with extension of interphalangeal joints and adduction and flexion of the meta- carpophalangeal joints) and feet (pedal spasm). Chovstek’s sign - demonstrated by tapping anterior to the ear, at the emergence of the facial nerve. A resultant twitch of the nose or lips suggests low calcium levels. 69 Textbook of medicine – khosla 6th edition

70. Sialolithiasis It is a common disease of salivary gland characterized by the obstruction of the salivary secretion by the calculus. These calculi generally consist of mixture of different calcium phosphates( mainly hydroxyapatite & carbonate-apatite ) together with an organic matrix. More commonly seen in submandibular gland duct. 70 Textbook of oral medicine by Anil Ghoms 2 nd edition

71. Dental Pulp stones They are tiny concretions that cab be found in the pulp chamber, the vascularized , central portion of the tooth. They contain matrix of organic material , upon which it deposits calcium in the form of carbonate apetite . Their presence is usually associated with old age pulp or poor pulpal health. Shafer’s textbook of oral pathology 7th edition 71

72. Calcium channel blockers 3 subclasses – 1. Phenyl alkylamine – Verapamil 2. Dihydropyridines – Nifidepine 3. Benzothiazipine – Diltiazem Pharmacological action – inhibit Ca mediated slow channel component of action potential in smooth/cardiac muscle cell. Essentials of medical pharmacology KD Tripathi 6th edition 72

73. Uses of CCB’S – Angina pectoris Hypertension Cardiac arrythmias Hypertrophic cardiomyopathy Premature labor- Nifedipine Suppress migraine & nocturnal leg cramps – Verapamil Raynaud’s disease – Nifedipine 73 Essentials of medical pharmacology KD Tripathi 6th edition

74. Conclusion Calcium is crucial for body physiological function. It is an essential intracellular signaling molecule & plays a variety of extracellular functions , thus the control of bodily calcium concentrations is vitally important. Calcium concentration must be tightly regulated to maintain the physiological stability by interaction between major organs & hormones. 74

75. Bibliography Guyton textbook of medical physiology – 11th edition Textbook of Medical Biochemistry – M N Chatterjea & Rana Shinde 6th edition Biochemistry by U Satyanarayana & U. Chakrapani 3rd edition . Essentials of medical pharmacology KD Tripathi 6th edition . Fundamentals of biochem – Dr. A.C.Deb 7th edition 75

76. 6.Textbook of oral medicine by Anil Ghoms . 7 .Shafer’s textbook of oral pathology 7th edition 8.http ://ods.od.nih.gov/factsheets/Calcium-HealthProfessional /- national institute of health office of dietary supplements ; cimsasia.com 9. Textbook of medicine – khosla 6th edition 76

77. Thank you 77