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MATABOLISM OF CALCIUM & PHOSPHOROUS

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YESANNA

MATABOLISM OF CALCIUM & PHOSPHOROUS

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Gandham. Rajeev
• Calcium metabolism
• Sources & RDA
• Factors affecting calcium absorption
• Biochemical functions
• Regulation of plasma calcium
• Disease states
• Case report
• Metabolism of phosphorous
• Sources & RDA
• Biochemical functions
• Disease states
• RGUHS questions
• Essential for
• Normal growth & maintenance of the body
• Calcification of bone
• Blood coagulation
• Neuromuscular irritability
• Acid-base equilibrium
• Fluid balance & osmotic regulation
• Daily requirement is >100 mg/day - macro minerals/macro elements
• Daily requirement is <100 mg/day - micro minerals/micro elements
Classification of minerals according to their essentiality
Major elements Minor elements
Calcium Iron
Magnesium Iodine
Phosphorous Copper
Sodium Manganese
Potassium Zinc
Chloride Molybdenum
Sulfur Selenium
Fluoride
Calcium metabolism
• Most abundant mineral.
• Total body calcium is about 1 to 1.5 kg.
• 99% is seen in bone together with phosphate & 1% in ECF
• Dietary Sources of calcium:
• Milk is a good source for calcium
• Egg, fish, cheese, beans, nuts, cabbage and vegetables are
good sources for calcium
Daily requirement of calcium
• Adult men & women = 500 mg/day
• Children’s = 1200 mg/day
• Pregnancy & lactation = 1500 mg/day
• Calcium in plasma is of 3 types
• Ionized or free or unbound calcium
• Bound calcium
• Complexed calcium
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MATABOLISM OF CALCIUM & PHOSPHOROUS

  • 2. • Calcium metabolism • Sources & RDA • Factors affecting calcium absorption • Biochemical functions • Regulation of plasma calcium • Disease states • Case report • Metabolism of phosphorous • Sources & RDA • Biochemical functions • Disease states • RGUHS questions
  • 3. • Essential for • Normal growth & maintenance of the body • Calcification of bone • Blood coagulation • Neuromuscular irritability • Acid-base equilibrium • Fluid balance & osmotic regulation • Daily requirement is >100 mg/day - macro minerals/macro elements • Daily requirement is <100 mg/day - micro minerals/micro elements
  • 4. Classification of minerals according to their essentiality Major elements Minor elements Calcium Iron Magnesium Iodine Phosphorous Copper Sodium Manganese Potassium Zinc Chloride Molybdenum Sulfur Selenium Fluoride
  • 5. Calcium metabolism • Most abundant mineral. • Total body calcium is about 1 to 1.5 kg. • 99% is seen in bone together with phosphate & 1% in ECF • Dietary Sources of calcium: • Milk is a good source for calcium • Egg, fish, cheese, beans, nuts, cabbage and vegetables are good sources for calcium
  • 6. Daily requirement of calcium • Adult men & women = 500 mg/day • Children’s = 1200 mg/day • Pregnancy & lactation = 1500 mg/day • Calcium in plasma is of 3 types • Ionized or free or unbound calcium • Bound calcium • Complexed calcium
  • 7. • Ionized or free or unbound calcium or diffusible: 5.5 mg/dl • In blood, 50% of plasma calcium is free & is metabolically active • It is required for • Maintenance of nerve function • Membrane permeability • Muscle contraction • Hormone secretion • Bound calcium or non diffusible: 4.5 mg/dl • 40% of plasma calcium is bound to proteins – albumin
  • 8. • Complexed calcium: 1 mg/dl • 10% of plasma calcium is complexed with anions including bicarbonate, phosphate, lactate & citrate • All the three forms of calcium in plasma remain in equilibrium with each other. • Normal Range: • The normal level of plasma calcium is 9-11 mg/dl • Urine calcium:100-250 mg/day
  • 9. Absorption • From upper small intestine - first & second part of duodenum. • About 40% of dietary calcium is absorbed. • Absorbed against a concentration gradient & requires energy. • Requires a carrier protein, helped by calcium-dependent ATPase.
  • 10. Factors causing increased absorption • Vitamin D: • Calcitriol induces the synthesis of carrier protein (Calbindin) in the intestinal epithelial cells & facilitates the absorption of calcium • Parathyroid hormone: • It increases calcium absorption through increased synthesis of calcitriol
  • 11. • Acidity favors calcium absorption (enhance solubility of calcium) • Amino acids: • Lysine & arginine increases calcium absorption • Amino acids increase the solubility of Ca-salts & thus its absorption
  • 12. Factors causing decreased absorption • Phytates oxalates: • Phytates & oxalates form insoluble Ca-salts & decreases the absorption. • High phosphate content will cause precipitation as calcium phosphate. • Alkaline condition is unfavorable for absorption. • Calcium forms insoluble soaps with fatty acids • Vitamin D deficiency states.
  • 13. Biochemical functions • Development of bones and teeth: • Bone is regarded as a mineralized connective tissue • Bones also act as reservoir for calcium • The bulk quantity of calcium is used for bone & teeth formation • Osteoblasts induce bone deposition & osteoclasts produce demineralization.
  • 14. • Muscles: • Calcium mediates excitation & contraction of muscles • Ca2+ interacts with troponin C to trigger muscle contraction • Calcium activates ATPase, increases action of actin & myosin and facilitates excitation-contraction coupling. • Calcium decreases neuromuscular irritability.
  • 15. • Nerve conduction: • It is necessary for transmission of nerve impulses • Blood coagulation: • Calcium is known as factor IV in blood coagulation process • Prothrombin contains γ-carboxyglutamate residues which are chelated by Ca2+ during the thrombin formation. • Calcium is required for release of certain hormones - insulin, parathyroid hormone, calcitonin & vasopressin
  • 16. • Activation of enzymes: • Calmodulin is a calcium binding regulatory protein. • Calmodulin can bind with 4 calcium ions & molecular weight of 17,000 • Calcium binding leads to activation of enzymes • Enzymes activated by Calcium • Glycogen synthase • Pancreatic lipase • Adenylate cyclase • Glycerol 3-P-DH • Pyruvate carboxylase • PDH & Pyruvate kinase
  • 17. • Second messenger: • Calcium & cAMP are second messengers for hormones e.g. epinephrine in liver glycogenolysis. • Calcium serves as a third messenger for some hormones e.g, ADH acts through cAMP & Ca2+ • Myocardium: • Ca2+ prolongs systole. • In hypercalcemia, cardiac arrest is seen in systole.
  • 18. Regulation of plasma calcium level • Dependent on the function of 3 main organs • Bone • Kidney • Intestine • 3 main hormones • Calcitriol • Parathyroid hormone • Calcitonin
  • 19. Regulation of plasma calcium level by Calcitriol • Role of calcitriol on bone: • In osteoblasts of bone, calcitriol stimulates calcium uptake for deposition as calcium phosphate • At low calcium levels, calcitriol along with parathyroid hormone increases the mobilization of calcium & phosphate from the bone • Causes elevation in the plasma calcium and phosphate
  • 20. Role of calcitriol on kidneys • Calcitriol minimizing the excretion of Ca2+ & phosphate by decreasing their excretion & enhancing reabsorption. • Role of calcitriol on intestine: • It increases intestinal absorption of Ca2+ & phosphate. • It binds with cytosolic receptor to form calcitriol-receptor complex • Complex interacts with DNA leading to the synthesis of a specific calcium binding protein • This protein increases calcium uptake by intestine
  • 21. Regulation by parathyroid hormone (PTH) • PTH is secreted by two pairs of parathyroid glands. • PTH (mol. wt. 95,000) is a single chain polypeptide, containing 84 amino acids. • It is synthesized as prepro PTH, whch is degraded to proPTH & finally to active PTH. • The rate of formation & secretion of PTH are promoted by low Ca2+ concentration.
  • 22. Mechanism of action of PTH • Action on the bone: • PTH causes decalcification or demineralization of bone, a process carried out by osteoclasts. • This is brought out by pyrophosphatase & collagenase • These enzymes result in bone resorption. • Demineralization ultimately leads to an increase in the blood Ca2+ level.
  • 23. Action on the kidney • PTH increases the Ca2+ reabsorption by kidney tubules • It is most rapid action of PTH to elevate blood Ca2+ levels • PTH promotes the production of calcitriol (1,25 DHCC) in the kidney by stimulating 1- hydroxyaltion of 25- hydroxycholecalciferol • Action on the intestine: • It increases the intestinal absorption of Ca2+ by promoting the synthesis of calcitriol.
  • 25. Calcitonin • Calcitonin is a peptide containing 32 amino acids. • It is secreted by parafollicular cells of thyroid gland. • The action of CT on calcium is antagonistic to that of PTH. • Calcitonin promotes calcification by increasing the activity of osteoblasts. • Calcitonin decreases bone resorption & increases the excretion of Ca2+ into urine • Calcitonin has a decreasing influence on blood calcium
  • 26. Calcitonin, calcitriol & PTH act together
  • 27. Hypercalcemia • The serum Ca2+ level >11 mg/dl is called as Hypercalcemia. • Causes: • Hyperparathyroidism: • Due to increased activity of parathyroid gland or PTH secreting tumor • Increase in calcium & ALP & decrease in phosphate levels. • Excretion of calcium & phosphorous in urine. • Determination of ionized Ca2+ (elevated to 6-9 mg/dl) is useful for diagnosis of hyperparathyroidism
  • 28. Clinical features of hypercalcemia • Neurological symptoms: • Depression, confusion, inability to concentrate • Generalized muscle weakness • Gastrointestinal problems • Anorexia, abdominal pain, nausea, vomiting & constipation • Renal feature: calcification of renal tissue • Increased myocardial contractility & susceptibility to factures.
  • 29. Hypocalcemia • Decreased serum Ca2+ < 8.8 mg/dl is called as hypocalcemia • Causes: • Hypoproteinaemia: • If albumin concentration in serum falls, total calcium is low because the bound fraction is decreased • Hypoparathyroidism: • The commonest cause is neck surgery, idiopathic.
  • 30. • Vitamin D deficiency: • May be due to malabsorption or little exposure to sunlight • Leads to bone disorders, osteomalacia & rickets • Renal disease: • In kidney diseases, the 1, 25 DHCC (calcitriol) is not synthesized due to impaired hydroxylation
  • 31. • Clinical features of hypocalcemia: • Enhanced neuromuscular irritability • Neurologic features • Tingling, tetany, numbness (fingers & toes), muscle cramps • Cardiovascular signs - abnormal ECG • Cataracts.
  • 32. Rickets • Rickets is a disorder of defective calcification of bones. • This may be due to a low levels of vitamin D in the body or due to a dietary deficiency of Ca2+ & P or both. • The concentration of serum Ca2+ & P may be low or normal • An increase in the activity of alkaline phosphatase is a characteristic feature of rickets.
  • 34. Osteoporosis • Characterized by demineraIization of bone resulting in the progressive loss of bone mass. • After the age of 40-45, Ca2+ absorption is reduced & Ca2+ excretion is increased; there is a net negative balance for Ca2+ • After the age of 60, osteoporosis is seen • There is reduced bone strength & an increased risk of fractures. • Decreased absorption of vitamin D & reduced levels of androgens/estrogens in old age are the causative factors.
  • 36. Case report • A 5 year old girl had bone deformities such as bow legs and pigeon chest. She had delayed eruption of teeth. The girl was from a strict vegetarian family and she used to take very low amount of milk. Interpret the following laboratory findings. Investigations Report Serum calcium 8.5 mg/dl Serum inorganic phosphate 2.2 mg/dl Serum alkaline phosphatase 175 IU/L Serum calcitriol 12 pg/ml (Reference Range: 15 – 60 pg/ml)
  • 38. • Human body contains - 1 kg of phosphorous • Body distribution: • 80% of phosphorous is found in bones & teeth in combination with calcium. • 15% of phosphorous is present in soft tissues, as a component of phospholipids, phosphoproteins, nucleic acids & nucleoproteins. • 1% is found in ECF, as inorganic form
  • 39. Dietary sources and RDA • The food rich in calcium is also rich in phosphorous • i.e. milk, cheese, beans, eggs, cereals, fish & meat • Milk is good source of phosphorous • RDA: • Adults: 800 mg/day • During pregnancy and lactation: 1,200 mg/day • Ca : P of 1:1 is recommended
  • 40. Biochemical functions • Phosphorous is essential for formation of bones & teeth • It is a constituent of hydroxyapatite in bone & provides structural support. • Formation & utilization of high energy phosphate compounds like • ATP, ADP, GTP, Creatine phosphate, etc. contains phosphorous. • Essential for the formation of • Phospholipids, phosphoproteins, nucleic acids, nucleotides
  • 41. • Component of nucleotide coenzymes – NAD+, NADP, ATP, ADP • Several enzymes & proteins are activated by phosphorylation & dephosphorylation. • Phosphate buffer system is important for maintenance of blood pH • Formation of phosphate esters - glucose-6-p.
  • 42. Absorption • 90% of dietary phosphorous is absorbed from small intestine. • Absorption is stimulated by both PTH & calcitriol. • Excretion: • 500 mg of phosphate is excreted through urine per day • Renal threshold for phosphorous is 2 mg/dl. • Normal range: • Plasma phosphorous: 2.5 to 4.5 mg/dl in adults • In children’s: 5.0 to 6.0 mg/dl
  • 43. • Calcium & phosphorous have reciprocal relationship. • In particular, if phosphate rises, calcium falls. • Fasting phosphate levels are higher • Postprandial decrease of phosphorous is due to the utilization of phosphorous for metabolism.
  • 44. Hypophosphataemia • Serum inorganic phosphate concentration <2.5 mg/dl is called as Hypophosphataemia • Causes: • Decreases intake, Decreased absorption, Increased loss: • In the treatment of Diabetes the effect of insulin in causing the shift of glucose into cells also enhances the transport of phosphate into cells, which may result into hypophosphataemia
  • 45. • Renal rickets is associates with low phosphate & increased ALP concentration. • Congenital defect of tubular phosphate reabsorption, e.g. Fanconi’s syndrome, in which phosphate is lost. • Symptoms: • Symptoms: • Hemolytic anemia, weakness, bone fractures, Muscle pain. • Rickets in children’s & osteoporosis in adults may develop.
  • 46. Hyperphosphataemia • Increase in serum inorganic phosphate levels than the normal levels is called as hyerphosphataemia • Causes: • Increased intestinal absorption, decreased renal excretion, cellular release of phosphorous. • Symptoms: • Chronic renal failure, soft tissue calcification.
  • 47. RGUHS Questions 1. Explain the sources, daily requirement, absorption, biochemical functions & disorders of calcium metabolism. 2. Blood calcium homeostasis. 3. Rickets & osteoporesis. 4. Metabolism of phosphorous.