Blood calcium

Blood Calcium

1. BLOOD CALCIUM BY ARCHANA.B FIRST YEAR PG

2. Introduction: Total calcium in the human body is about 1-1.5 kg of which 99% is seen in the bones and 1% in the extracellular fluids. If the daily requirements of any element is more than 100mg then such elements are called major elements or macro minerals.

3. Minerals present in our body are classified into Major minerals ( macro minerals) Trace elements (micro minerals)

4. IMPORTANCE OF CALCIUM Calcium is very essential for many activities in the body such as: 1. Bone and teeth formation 2. Neuronal activity 3. Skeletal muscle activity 4. Cardiac activity 5. Smooth muscle activity 6. Secretory activity of the glands 7. Cell division and growth 8. Coagulation of blood

5. Sources of calcium: Milk is a good source of calcium. Egg, fish and vegetables are medium sources Cereals contain a small quantity of calcium which makes up the major source of calcium for the indian population.

6. C alcium is available in several foodstuffs. Percentage of calcium in different food substance is: Whole milk = 10% Low fat milk = 18% Cheese = 27% Other dairy products = 17% Vegetables = 7% Other substances such as meat, egg, grains, sugar, coffee, tea, chocolate, etc. = 21% Besides dietary calcium, blood also gets calcium from bone by resorption.

7. Daily requirement: After te age of 50 there is general tendency of osteoporesis that can be prevented by increased calcium intake with vitamin D.

8. TYPES OF CALCIUM: Calcium in Plasma: Calcium is present in three forms in plasma: I . Ionized or diffusible calcium : Found freely in plasma and forms about 50% of plasma calcium. It is essential for vital functions such as neuronal activity, muscle contraction, cardiac activity, secretions in the glands, blood coagulation, etc. I I . Non-ionized or non-diffusible calcium : Present in non-ionic form such as calcium bicarbonate. It is about 8% to 10% of plasma calcium I II . Calcium bound to albumin: Forms about 40% to 42% of plasma calcium.

9. Calcium in Bones Calcium is constantly removed from bone and deposited in bone. Bone calcium is present in two forms: I. Rapidly exchangeable calcium or exchangeable calcium: Available in small quantity in bone and helps to maintain the plasma calcium level I I . Slowly exchangeable calcium or stable calcium: Available in large quantity in bones and helps in bone remodeling.

10. Absorption and excretion of calcium: Calcium taken through dietry sources is absorbed from the GI tract into blood and distributed to various parts of the body. Depening upon the blood level the calcium is either deposited in the bone or removed from the bone Calcium is excreated from the body through urine and feces.

11. Absorption from GI tract: Calcium is absorbed from duodenum by carrier mediated active transport and from the rest of the small intestine by facilitated diffusion. Vit- D is essential for absorption of calcium from the GI tract.

12. Excretion: About 1000mg of calcium is excreated daily. While passing through kidney large quantity of calcium is filtered in the glomerulus From the filterate 98-99% of calcium is reasorbed from the renal tubles into the blood and only and small quantity is excreated in the urine Most of the filtered cacium is resorbed in the distal convoluted tubules and proximal part of the collecting duct

13. In distal convuluted tubule parathormone increases the resorption of calcium In collecting duct vitamine D increases the the calcium resorption and calcitonin decreases resorption. Out of this 900mg is excreated through feces and 100 mg through urine

14. Process of calcium metabolism

15. REGULATION OF BLOOD CALCIUM LEVEL Blood calcium level is regulated mainly by three hormones: 1. Parathormone 2. 1,25-dihydroxycholecalciferol (calcitriol) 3. Calcitonin.

16. Regulation of blood calcium:

17. In calcium metabolism Parathormone

18. Parathormone is a protein hormone secreted by parathyroid gland and its main function is to increase the blood calcium level by mobilizing calcium from bone . Parathormone secreted by parathyroid gland is essential for the maintenance of blood calcium level within a very narrow critical level. Maintenance of blood calcium level is necessary because calcium is an important inorganic ion for many physiological functions

19. Human beings have four parathyroid glands, which are situated on the posterior surface of upper and lower poles of thyroid gland .

20. ACTIONS OF PARATHORMONE ON BLOOD CALCIUM LEVEL Primary action of PTH is to maintain the blood calcium level within the critical range of 9 to 11 mg/ dL . The blood calcium level has to be maintained critically because, it is very important for many of the activities in the body. PTH maintains blood calcium level by acting on: 1. Bones 2. Kidney 3. Gastrointestinal tract.

21. 1. On Bone Parathormone enhances the resorption of calcium from the bones ( osteoclastic activity) by acting on osteoblasts and osteoclasts of the bone. Resorption of calcium from bones occurs in two phases: i. Rapid phase ii. Slow phase.

22. 2. On Kidney PTH increases the reabsorption of calcium from the renal tubules along with magnesium ions and hydrogen ions. It increases calcium reabsorption mainly from distal convoluted tubule and proximal part of collecting duct. PTH also increases the formation of 1,25-dihydroxycholecalciferol (activated form of vitamin D) from 25-hydroxycholecalciferol in kidneys.

23. 3. On Gastrointestinal Tract PTH increases the absorption of calcium ions from the GI tract indirectly. It increases the formation of 1,25-dihydroxycholecalciferol in the kidneys. This vitamin, in turn increases the absorption of calcium from GI tract. Thus, the activated vitamin D is very essential for the absorption of calcium from the GI tract. And PTH is essential for the formation of activated vitamin D.

24. Role of PTH in the activation of vitamin D Vitamin D is very essential for calcium absorption from the GI tract. But vitamin D itself is not an active substance. Instead, vitamin D has to be converted into 1, 25-dihydroxycholecalciferol in the liver and kidney in the presence of PTH. The 1,25-dihydroxycholecalciferol is the active product.

25. Role of PTH on Blood Level of Calcium Blood level of calcium is the main factor regulating the secretion of PTH. Parathormone secretion is inversely proportional to blood calcium level. Increase in blood calcium level decreases PTH secretion.

26. Conditions when PTH secretion decreases are: 1. Excess quantities of calcium in the diet 2. Increased vitamin D in the diet 3. Increased resorption of calcium from the bones, caused by some other factors such as bone diseases. On the other hand, decrease in calcium ion concentration of blood increases PTH secretion, as in the case of rickets, pregnancy and in lactation.

27. In calcium metabolsm 1,25-dihydroxycholecalciferol (calcitriol)

28. Calcitriol is a steroid hormone synthesized in kidney. It is the activated form of vitamin D. Its main action is to increase the blood calcium level by increasing the calcium absorption from the small intestine

29. Activation of vitamin D There are various forms of vitamin D. But, the most important one is vitamin D3. It is also known as cholecalciferol . Vitamin D3 is synthesized in the skin from 7-dehydrocholesterol, by the action of ultraviolet rays from the sunlight. It is also obtained from dietary sources. The activation of vitamin D3 occurs in two steps

30. First step Cholecalciferol (vitamin D3) is converted into 25-hydroxycholecalciferol in the liver. This process is limited and is inhibited by 25-hydroxycholecalciferol itself by feedback mechanism.

31. Second step 25-hydroxycholecalciferol is converted into 1,25- dihydroxycholecalciferol ( calcitriol ) in kidney. It is the active form of vitamin D3. This step needs the presence of PTH.

32. Role of Calcium Ion in Regulating 1, 25-Dihydroxycholecalciferol When blood calcium level increases, it inhibits the formation of 1,25 dihydroxycholecalciferol. Increase in calcium ion concentration decreases the PTH secretion, which in turn suppresses the conversion of 25-hydroxycholecalciferol into 1,25-dihydroxycholecalciferol.

33. In calcium metabolism CALCITONIN

34. Calcitonin secreted by parafollicular cells of thyroid gland. Thyroid gland is a calcium-lowering hormone. It reduces the blood calcium level mainly by decreasing bone resorption

35. ACTIONS OF CALCITONIN On Blood Calcium Level Calcitonin plays an important role in controlling the blood calcium level. It decreases the blood calcium level and thereby counteracts parathormone. Calcitonin reduces the blood calcium level by acting on bones, kidneys and intestine.

36. On bones Calcitonin stimulates osteoblastic activity and facilitates the deposition of calcium on bones. At the same time, it suppresses the activity of osteoclasts and inhibits the resorption of calcium from bones. It inhibits even the development of new osteoclasts in bones. On kidney Calcitonin increases excretion of calcium through urine, by inhibiting the reabsorption from the renal tubules. On intestine Calcitonin prevents the absorption of calcium from intestine into the blood.

37. Effects of Other Hormones In addition to the above mentioned three hormones, growth hormone and glucocorticoids also influence the calcium level . Glucocorticoids(cortisol) decrease blood calcium by inhibiting intestinal absorption and increasing the renal excretion of calcium. Growth hormone increases the blood calcium level by increasing the intestinal calcium absorption. It is also suggested that it increases the urinary excretion of calcium. However, this action is only transient.

38. In blood calcium regulation Other factors

39. Phosphorus: There is a reciprocal relationship of calcium with phosphorus. Ionic products of calcium and phosphrous in the serum is is kept as a constant i.e, Calcium= 10mg/dL and Phosohorus = 4mg/dL. When phosphorus content in the blood is increased the calcium content is lowered (tetany) Serum proteins: In hypoalbuminemia the total calcium is decreased.

40. Alkalosis and acidosis: Alkalosis favors binding of more calcium with proteins with constant lowering of ionised calcium in the serum so calcium deficiency may be manifested Acidosis favors ionisation of calcium.

41. FUNCTIONS OF CALCIUM

42. Activation of enzymes: Many hormones act by increasing the calcium ion, which fucntions as second messenger along with another protein called calmodulin or troponin C. Calmodulin is present in smooth muscles and troponin C is present in skeletal muscles. Calcium- calmodulin complex activates various enzymes in the cell, which cause the physiological responses. Eg: myosin kinase in smooth muscle. c Ca ++ + Calmodulin Ca- bound-calmodulin Kinase Active kinase Enzyme Phosphorylated enzyme Biological effect

43. Muscles: Sarcotubular system is a system of membranous structures in the form of vesicles and tubules in the sarco plasm of the muscle fiber. It surrounds the myofibrils embedded in the sarcoplasm Sarcotubular system is formed mainly by two types of structures: 1. T tubules 2. L tubules or sarcoplasmic reticulum.

44. Calcium mediates excitation and contraction of muscle fibres. An ATP dependent calcium pump also functions to regulate muscle contraction. In resting the concentration of calcium ions around the muscle fibres is low after stimulation there is sudden release of calcium ions that triggers muscle contraction. Excitation-contraction coupling

45. Muscle relaxation

46. Nerve conduction: Calcium is necessary for transmission of nerve impulses from the pre synaptic to post synaptic region

47. Secretion of hormones : Calcium mediates secreation of various hormones like insulin, parathyroid,calcitonin, adrenalin etc., Calcium acts as a cholagogue that is it incrases the release of bile into the intestine from the gall bladder.

48. Prostaglandins increase the force of uterine contractions by elevating the concentration of calcium ions in the smooth muscle fibers of uterus. Calcium ions increase the release of serotonin, which facilitates the synaptic transmission to a great extent, leading to memory storage

49. Maintenance of Milk Secretion or Galactopoiesis Galactopoiesis depends upon the hormones like growth hormone, thyroxine and cortisol , which are essential for continuous supply of glucose, amino acids, fatty acids, calcium and other substances necessary for the milk production BITTER TASTE RECEPTOR Bitter receptor is a G-protein coupled receptor . In bitter receptor, the sour substances activate phospholipase C through G proteins. It causes production of inositol triphosphate (IP3), which initiates depolarization by releasing calcium ions.

50. Mineralization Mineralization is the process by which the minerals are deposited on bone matrix. Mineralization starts about 10 to 12 days after the formation of osteoid . First, a large quantity of calcium phosphate is deposited. Afterwards, the hydroxide and bicarbonate ions are gradually added causing the formation of hydroxyapatite crystals. The process of mineralization is accelerated by the enzyme alkaline phosphatase , secreted by osteoblast . The process also requires the availability of adequate amount of calcium and phosphate in the ECF.

51. Vascular permiability: Calcium decreases the passage of serum through capillaries. Thus calcium is clinically used to reduce allergic exudates. Myocardium: Ca 2+ prolongs systole Calpains: Calpains are calcium dependent cysteine proteases that modulate cellular function. Calpains are involved in apoptosis process also.

52. Calcium in blood

53. Inorganic substances present in body fluids are sodium, potassium, calcium, magnesium, chloride, bicarbonate, phosphate and sulfate. Substance ECF ICF Calcium 5 mEq/L 1 mEq/L Platelet Granules Granules present in cytoplasm of platelets are of two types: 1. Alpha granules 2. Dense granules

54. Adhesiveness is the property of sticking to a rough surface. factors which accelerate adhesiveness are collagen, thrombin, ADP, Thromboxane A2, calcium ACTIVATORS OF PLATELETS 1. Collagen, which is exposed during damage of blood vessels 2. von Willebrand factor 3. Thromboxane A2 4. Platelet-activating factor 5. Thrombin 6. ADP 7. Calcium ions 8. P- selectin : Cell adhesion molecule secreted from endothelial cells 9. Convulxin: Purified protein from snake venom.

55. FACTORS INVOLVED IN BLOOD CLOTTING Thirteen clotting factors are identified: Factor I Fibrinogen Factor II Prothrombin Factor III Thromboplastin (Tissue factor) Factor IV Calcium Factor V Labile factor ( Proaccelerin or accelerator globulin) Factor VI Presence has not been proved Factor VII Stable factor Factor VIII Antihemophilic factor ( Antihemophilic globulin) Factor IX Christmas factor Factor X Stuart-Prower factor Factor XI Plasma thromboplastin antecedent Factor XII Hageman factor (Contact factor) Factor XIII Fibrin-stabilizing factor (Fibrinase).

56. Intrinsic and extrinsic pathways:

57. Anti coagulants’ action: HEPARIN: Heparin is a naturally produced anticoagulant in the body. It is produced by mast cells which are the wandering cells present immediately outside the capillaries in many tissues or organs that contain more connective tissue. Commercial preparation is available in liquid form or dry form as sodium, calcium, ammonium or lithium salts. 2. EDTA Ethylenediaminetetraacetic acid (EDTA) is a strong anticoagulant. These substances prevent blood clotting by removing calcium from blood.

58. OXALATE COMPOUNDS Oxalate compounds prevent coagulation by forming calcium oxalate, which is precipitated later. Thus, these compounds reduce the blood calcium level. CITRATES: Citrate combines with calcium in blood to form insoluble calcium citrate. Like oxalate, citrate also removes calcium from blood and lack of calcium prevents coagulation.

59. PROTHROMBIN TIME Prothrombin time (PT) is the time taken by blood to clot after adding tissue thromboplastin to it. Blood is collected and oxalated so that, the calcium is precipitated and prothrombin is not converted into thrombin. Thus, the blood clotting is prevented. Then a large quantity of tissue thromboplastin with calcium is added to this blood. Calcium nullifies the effect of oxalate. The tissue thromboplastin activates prothrombin and blood clotting occurs.

60. PARTIAL PROTHROMBIN TIME OR ACTIVATED PROTHROMBIN TIME Partial prothrombin time (PPT) is the time taken for the blood to clot after adding an activator such as phospholipid , along with calcium to it. It is also called activated partial prothrombin time (APTT). This test is useful in monitoring the patients taking anticoagulant drugs. It is carried out by observing clotting time after adding phospholipid , a surface activator and calcium to a patient’s plasma.

61. In calcium metabolism Disorders

62. Rigor: Rigor refers to shortening and stiffening of muscle fibers. Calcium rigor: Due to increased calcium content. It is reversible. Rigor mortis: Soon after death, the cell membrane becomes highly permeable to calcium enters the muscle fibers and promotes the formation of actomyosin complex resulting in contraction of the Muscles. Stoppage of the heart in systole, due to hypercalcemia is called the calcium rigor. EATON-LAMBERT SYNDROME Eaton-Lambert syndrome is also an autoimmune disorder of neuromuscular junction. It is caused by antibodies to calcium channels in axon terminal .

63. HYPOCALCEMIA decrease in blood calcium level. Hypocalcemic Tetany Tetany is an abnormal condition characterized by violent and painful muscular spasm (spasm = involuntary muscular contraction), particularly in feet and hand. It is because of hyperexcitability of nerves and skeletal muscles due to calcium deficiency.

64. Cardiovascular changes i . Dilatation of the heart ii. Prolonged duration of ST segment and QT interval in ECG iii. Arrhythmias (irregular heartbeat) iv. Hypotension v. Heart failure.

65. Other features i . Decreased permeability of the cell membrane ii. Dry skin with brittle nails iii. Hair loss iv. Grand mal, petit mal or other seizures v. Signs of mental retardation in children or dementia in adults

66. Hypercalcemia Hypercalcemia is the increase in plasma calcium level. It occurs in hyperparathyroidism because of increased resorption of calcium from bones. Depressive effects of hypercalcemia are noticed when the blood calcium level increases to 12 mg/ dL . The condition becomes severe with 15 mg/ dL and it becomes lethal when blood calcium level reaches 17 mg/dL. It increases the excitability and contractility of the heart muscle. In clinical conditions, the effect of hypercalcemia is very rare .

67. Osteoporosis Osteoporosis is the bone disease characterized by the loss of bone matrix and minerals. Osteoporosis means - ‘porous bones’ Manifestations of osteoporosis Loss of bone matrix and minerals leads to loss of bone strength, associated with architectural deterioration of bone tissue. Ultimately, the bones become fragile with high risk of fracture. Commonly affected bones are vertebrae and hip.

68. Patients with chronic periodontitis present increased risk for osteoporosis: A population-based cohort study in Taiwan. - Mau LP et al. JPR-2017 Association of osteoporosis and bone medication with the periodontal condition in elderly women. - Penoni Dc et al - 2016

69. Rickets Rickets is the bone disease in children, characterized by inadequate mineralization of bone matrix. It occurs due to vitamin D deficiency. Deficiency of vitamin D affects the reabsorption of calcium and phosphorus from renal tubules, resulting in calcium deficiency. It causes inadequate mineralization of epiphyseal growth plate in growing bones.

70. Osteomalacia Rickets in adults is called osteomalacia or adult rickets. Causes of osteomalacia Osteomalacia occurs because of deficiency of vitamin D. It also occurs due to prolonged damage of kidney (renal rickets).

71. Features of osteomalacia i. Vague pain ii. Tenderness in bones and muscles iii. Myopathy leading to waddling gait . In waddling gait, the feet are wide apart and walk resembles that of a duck iv. Occasional hypoglycemic tetany.

72. Other conditions related to calcium: Osteo petrosis Hyper thyroidism Hypo thyroidism Kidney stones Gall stones ( Cholelithiasis ) Hyper-reflexia and convulsions Carpopedal spasm Laryngeal stridor