Calcium metabolism by Dr Anurag Yadav

D
Dr Anurag YadavAssociate Professor, MD Biochemistry and consultant Biochemist à MNR Medical College & Hospital, Sangareddy, Hyderabad - TS
CALCIUM METABOLISM
Dr
Anurag
Yadav
Dr Anurag Yadav
MBBS, MD
Assistant Professor
Department of Biochemistry
Instagram page –biochem365
Email: dranurag.y.m@gmail.com
A naturally occurring, homogeneous
inorganic solid substance having a definite
chemical composition and characteristic
crystalline structure, color, and hardness.
Dr
Anurag
Yadav
FUNCTIONS
 Medium for cell activity – muscle & nerve cell
excitability, permeability of cell membrane.
 Involved in maintenance of body fluid
 They are structural elements in body – bone &
teeth
 Minerals are part of physiological compounds ---
Iron of Hb, Iodine of Thyroxine
 Cofactors of enzymes ---
Dr
Anurag
Yadav
 Cu- ceruloplasmin, tyrosinse
 Zn –DNA RNA Polymerase, Alc DH
 Iron – Cyt oxidase, catalase, peroxidase
 Mg –hexoKinase
 Se – Glu peroxidase
 Mo – xanthine oxidase
 Ni – urease
Dr
Anurag
Yadav
Macrominerals
Daily requirment > 100mg
Microminerals / Trace elements
Daily requirment < 100mg
Dr
Anurag
Yadav
Major elements
Calcium
Magnesium
Phosphorus
Sodium
Potassium
Chloride
Sulfur
Trace elements
Iron
Iodine
Copper
Manganese
Zinc
Molybdenium
Selenium
Fluoride
Dr
Anurag
Yadav
CALCIUM
Dr
Anurag
Yadav
 Total body calcium
 1-1.5 Kg
 99%-bone 1% ECF
Source
 Milk – 100mg in 100mL
 Egg, Fish, Vegetables, Cereals
Requirment
 Adult – 500mg/day
 Children – 1200mg/day
 Pregnancy Lactation – 1500mg/day
 Elderly – 1500mg/day + Vit D –
20microgm/day
Dr
Anurag
Yadav
ABSORPTION
Duodenum
Active transport
Requires calcium binding protein
Factors affecting absorption
Soluble calcium present
pH
Calcium – phosphorus ratio
Fat digestion & absorption
PTH & Vit D
Dr
Anurag
Yadav
Increased absorption
Vit D – synthesis of Calbindin
PTH – activate Vit D
Acidity
Amino acids – arginine and lysine
Inhibit absorption
Phytic acid - cereals
Oxalates – leafy vegetables
Malabsorption syndrome
High phosphates = calcium-
phosphate
Chronic renal failure, Coeliac disease
Dr
Anurag
Yadav
FUNCTIONS OF CALCIUM
Intracellular Calcium
Muscle contraction
 Initiated by binding of calcium to Troponine
Release of hormones, neurotransmitter
 Influx of calcium from extracellular space into
the neurons causes release of neurotransmitter
into synaptic cleft by exocytosis
Action of enzymes
 Calcium ions stabilize the active conformation
of the enzyme
Cell division
 Involved in Mitosis
Dr
Anurag
Yadav
Extracellular Calcium
Maintenance of intracellular calcium
 Calcium in bone acts as reservoir helps to
maintain extracellular fluid calcium
concentration
Bone mineralization
 99% is deposited as Hydroxyapatite crystal
Blood coagulation
 Inactive prothrombin to active thrombin
Membrane excitability
 Ca++ ions activate Na channels decreased Ca
decreased Na channel activity – Tetany
Membrane potential
Dr
Anurag
Yadav
Calcium levels
9-11mg/dL
3 forms
Free/ Ionic/Unbound calcium
 50% ---- 5mg/dL metabolically active
Bound
 40% ---- 4mg/dL bound to albumin
Complexed calcium
 10% complexed with anions
Bicarbonate, Phosphate, Citrate
Dr
Anurag
Yadav
Regulation of Calcium levels
3 organs
Bone
Kidney
Intestine
3 Hormones
Parathyroid
Vit D
Calcitonin
Dr
Anurag
Yadav
3 processes
Absorption of Calcium from the
intestine – Vit D
Reabsorption of Calcium from the
Kidney – PTH & Vit D
Demineralization of the bone --- PTH
Dr
Anurag
Yadav
1) Vitamin D
Active form – 1, 25 dihydroxy
cholecalciferol / Calcitriol
In Intestine
Absorption of Calcium from intestine
Dr
Anurag
Yadav
In BONE
 Calcitriol stimulates osteoblasts
 Osteoblasts secrete Alkaline phosphatase
 Local concentration of phosphates is
increased
 When ionic product of Calcium &
Phosphorus increases MINERALIZATION
takes place
In RENAL TUBULES
 Increases the reabsorption of Calcium &
Phosphorus
Dr
Anurag
Yadav
2) Parathyroid hormone PTH
 Secreted by parathyroid glands
 PTH secretion is controled by negative
feed back by the ionized calcium in the
serum
 Acts via cAMP
Dr
Anurag
Yadav
PTH action on bones
Demineralization
Induces phosphatases in osteoclasts
Osteoclasts release lactate in the
surroundin– solubilizes calcium
Increases secretion of Collagenase from
osteoclast --- loss of matrix
Dr
Anurag
Yadav
PTH action on Kidney
Decrease renal excretion of calcium by
increasing the reabsorption
Increased renal excretion of Phosphates
PTH action on Intestine
Increases Calcium absorption via Vit D
by activating Vit D
Stimulates 1 hydroxylation in the
Kidney
Dr
Anurag
Yadav
Dr
Anurag
Yadav
3) Calcitonin
Secreted by thyroid parafollicular cells
Decrease Calcium levels
Inhibits resorption of bone
Decreases activity of osteoclasts &
increases activity of osteoblasts
Increases Excretion of Ca &
Phosphorus
Dr
Anurag
Yadav
Dr
Anurag
Yadav
4) Phosphorus
Reciprocal relationship
Ionic product of calcium & phosphorus is
kept constant --- 40
Renal failure phosphorus excretion
decreased --- increase in phosphorus & Ca
level decreased
5) Children
Upper limit
Ionic product 50
Dr
Anurag
Yadav
6) Serum proteins
Hypoalbuminemia – decreased total
calcium
0.8mg of Ca reduced per gm/dL decrease
in albumin
Metabolically active form normal
7) Alkalosis & Acidosis
Alkalosis favours binding of Ca to
proteins --- decrease in ionic Ca
Acidosis favours ionization
Dr
Anurag
Yadav
Hypercalcemia
Ca >11mg/dL
Causes
Hyperparathyroidism
Multiple myeloma
Pagets disease
Metastatic carcinoma of the bone
Prolonged immobilization
Drugs –
 thiazide diuretics – reabsorpion of Ca
 Excess Vit D , IV Ca
Dr
Anurag
Yadav
Dr
Anurag
Yadav
Dr
Anurag
Yadav
Dr
Anurag
Yadav
Symptoms
Nausea, Vomiting
Confusion, depression
Osteoporosis
Renal stones
Ectopic calcification & pancreatitis
Blood alkaline phosphatase is
elevated
Dr
Anurag
Yadav
Hypocalcimea
 Ca < 8.8mg/dL
 Ca levels <7.5 Tetany
Causes
 Deficiency of Vit D
 Hypoparathyroidism
 Medullary carcinoma of thyroid – increased
Calcitonin
 Decreased absorption
 Renal failure – increased phosphorus levels
 Hypoalbuminemia
Dr
Anurag
Yadav
Symptoms
 Neuromascular irritability
 Muscle cramps
 Seizures
 Bradycardia
 Prolonged QT Interval
Tetany
 Carpopedal spasm
 Laryngismus & stridor
 Chvostek’s sign +ve
 Trousseu’s sign +ve
Dr
Anurag
Yadav
Dr
Anurag
Yadav
Carpopedal spasm
Chvostek’s sign
Trousseus sign
 Hypocalcemia can be treated by
 Oral calcium with vitamin D supplementation
 Underlying cause should be treated.
 Tetany needs IV calcium (usually 10 mL 10% calcium
gluconate over 10 minutes, followed by slow IV
infusion. IV calcium should be given only very slowly.
Dr
Anurag
Yadav
DISORDERS RELATED
Osteoporosis
Osteopetrosis
Pagets disease
Renal osteodystrophy
Dr
Anurag
Yadav
OSTEOPOROSIS
 After the age of 40–45, calcium absorption is
reduced and calcium excretion is increased
 there is a net negative balance for calcium. This
is reflected in demineralization.
 After the age of 60, osteoporosis is seen.
 reduced bone strength and an increased risk of
Fractures is seen in patients.
 Decreased absorption of vitamin D and reduced
levels of androgens/estrogens in old age are the
causative factors.
Dr
Anurag
Yadav
Osteopetrosis
 It is otherwise called marble bone disease. There is
increased bone density.
 It is due to mutation in gene encoding carbonic
anhydrase type II.
 The deficiency of the enzyme in osteoclasts leads to
inability of bone resorption.
Paget’s Disease
 Localized disease of bone characterized by
osteoclastic bone resorption followed by disordered
replacement of bone. It is common in people above
40 and may affect one or several bones. Familial
incidence is also reported.
 Bone markers are useful in monitoring response to
treatment using bisphosphonates.
Dr
Anurag
Yadav
Renal Osteodystrophy
 Secondary hyperparathyroidism as a
consequence of persistent hypocalcemia causes
high turnover bone disease, osteitis fibrosa.
 Osteomalacia may result (low bone turnover) due
to defective synthesis of 1,25 DHCC
Dr
Anurag
Yadav
MARKERS OF BONE DISEASE
 Metabolic bone diseases result from an imbalance
between bone resorption and bone formation.
 Osteopenia is more common than excess bone
formation.
Dr
Anurag
Yadav
GENERAL MARKERS OF BONE DISEASE
 Serum Calcium,
 Serum Inorganic Phosphorus,
 Serum Magnesium And
 Urinary Excretion Of Calcium And Phosphorus,
 Total Alkaline Phosphatase And Total Acid
Phosphatase Levels.
 These are the routine tests of bone metabolism.
 Vitamin D nutrition should be determined by
measuring serum 25-hydroxy vitamin D.
 PTH measurement would be required if serum
calcium is abnormal.
Dr
Anurag
Yadav
Markers of bone resorption Markers of bone formation
Telopeptide
•Serum carboxy terminal
telopeptide of type I collagen
•N-telopeptide of type I collagen
Serum bone specific isoenzyme of
alkaline phosphatase (sBAP)
Pyridinium cross links derived
from collagen
Serum osteocalcin (s-OC)
Tartrate resistant acid
phosphatase (TRAP)
Serum midportion of osteocalcin
(sm-OC)
Urinary hydroxyproline excretion Procollagen type 1 peptidase
Serum intact osteocalcin (s-OC)
Serum amino-terminal propeptide
of type I collagen (PINP)
Dr
Anurag
Yadav
Dr Anurag Yadav
MBBS, MD
Assistant Professor
Department of Biochemistry
Instagram page –biochem365
Email: dranurag.y.m@gmail.com
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Calcium metabolism by Dr Anurag Yadav

  • 1. CALCIUM METABOLISM Dr Anurag Yadav Dr Anurag Yadav MBBS, MD Assistant Professor Department of Biochemistry Instagram page –biochem365 Email: dranurag.y.m@gmail.com
  • 2. A naturally occurring, homogeneous inorganic solid substance having a definite chemical composition and characteristic crystalline structure, color, and hardness. Dr Anurag Yadav
  • 3. FUNCTIONS  Medium for cell activity – muscle & nerve cell excitability, permeability of cell membrane.  Involved in maintenance of body fluid  They are structural elements in body – bone & teeth  Minerals are part of physiological compounds --- Iron of Hb, Iodine of Thyroxine  Cofactors of enzymes --- Dr Anurag Yadav
  • 4.  Cu- ceruloplasmin, tyrosinse  Zn –DNA RNA Polymerase, Alc DH  Iron – Cyt oxidase, catalase, peroxidase  Mg –hexoKinase  Se – Glu peroxidase  Mo – xanthine oxidase  Ni – urease Dr Anurag Yadav
  • 5. Macrominerals Daily requirment > 100mg Microminerals / Trace elements Daily requirment < 100mg Dr Anurag Yadav
  • 8.  Total body calcium  1-1.5 Kg  99%-bone 1% ECF Source  Milk – 100mg in 100mL  Egg, Fish, Vegetables, Cereals Requirment  Adult – 500mg/day  Children – 1200mg/day  Pregnancy Lactation – 1500mg/day  Elderly – 1500mg/day + Vit D – 20microgm/day Dr Anurag Yadav
  • 9. ABSORPTION Duodenum Active transport Requires calcium binding protein Factors affecting absorption Soluble calcium present pH Calcium – phosphorus ratio Fat digestion & absorption PTH & Vit D Dr Anurag Yadav
  • 10. Increased absorption Vit D – synthesis of Calbindin PTH – activate Vit D Acidity Amino acids – arginine and lysine Inhibit absorption Phytic acid - cereals Oxalates – leafy vegetables Malabsorption syndrome High phosphates = calcium- phosphate Chronic renal failure, Coeliac disease Dr Anurag Yadav
  • 11. FUNCTIONS OF CALCIUM Intracellular Calcium Muscle contraction  Initiated by binding of calcium to Troponine Release of hormones, neurotransmitter  Influx of calcium from extracellular space into the neurons causes release of neurotransmitter into synaptic cleft by exocytosis Action of enzymes  Calcium ions stabilize the active conformation of the enzyme Cell division  Involved in Mitosis Dr Anurag Yadav
  • 12. Extracellular Calcium Maintenance of intracellular calcium  Calcium in bone acts as reservoir helps to maintain extracellular fluid calcium concentration Bone mineralization  99% is deposited as Hydroxyapatite crystal Blood coagulation  Inactive prothrombin to active thrombin Membrane excitability  Ca++ ions activate Na channels decreased Ca decreased Na channel activity – Tetany Membrane potential Dr Anurag Yadav
  • 13. Calcium levels 9-11mg/dL 3 forms Free/ Ionic/Unbound calcium  50% ---- 5mg/dL metabolically active Bound  40% ---- 4mg/dL bound to albumin Complexed calcium  10% complexed with anions Bicarbonate, Phosphate, Citrate Dr Anurag Yadav
  • 14. Regulation of Calcium levels 3 organs Bone Kidney Intestine 3 Hormones Parathyroid Vit D Calcitonin Dr Anurag Yadav
  • 15. 3 processes Absorption of Calcium from the intestine – Vit D Reabsorption of Calcium from the Kidney – PTH & Vit D Demineralization of the bone --- PTH Dr Anurag Yadav
  • 16. 1) Vitamin D Active form – 1, 25 dihydroxy cholecalciferol / Calcitriol In Intestine Absorption of Calcium from intestine Dr Anurag Yadav
  • 17. In BONE  Calcitriol stimulates osteoblasts  Osteoblasts secrete Alkaline phosphatase  Local concentration of phosphates is increased  When ionic product of Calcium & Phosphorus increases MINERALIZATION takes place In RENAL TUBULES  Increases the reabsorption of Calcium & Phosphorus Dr Anurag Yadav
  • 18. 2) Parathyroid hormone PTH  Secreted by parathyroid glands  PTH secretion is controled by negative feed back by the ionized calcium in the serum  Acts via cAMP Dr Anurag Yadav
  • 19. PTH action on bones Demineralization Induces phosphatases in osteoclasts Osteoclasts release lactate in the surroundin– solubilizes calcium Increases secretion of Collagenase from osteoclast --- loss of matrix Dr Anurag Yadav
  • 20. PTH action on Kidney Decrease renal excretion of calcium by increasing the reabsorption Increased renal excretion of Phosphates PTH action on Intestine Increases Calcium absorption via Vit D by activating Vit D Stimulates 1 hydroxylation in the Kidney Dr Anurag Yadav
  • 22. 3) Calcitonin Secreted by thyroid parafollicular cells Decrease Calcium levels Inhibits resorption of bone Decreases activity of osteoclasts & increases activity of osteoblasts Increases Excretion of Ca & Phosphorus Dr Anurag Yadav
  • 24. 4) Phosphorus Reciprocal relationship Ionic product of calcium & phosphorus is kept constant --- 40 Renal failure phosphorus excretion decreased --- increase in phosphorus & Ca level decreased 5) Children Upper limit Ionic product 50 Dr Anurag Yadav
  • 25. 6) Serum proteins Hypoalbuminemia – decreased total calcium 0.8mg of Ca reduced per gm/dL decrease in albumin Metabolically active form normal 7) Alkalosis & Acidosis Alkalosis favours binding of Ca to proteins --- decrease in ionic Ca Acidosis favours ionization Dr Anurag Yadav
  • 26. Hypercalcemia Ca >11mg/dL Causes Hyperparathyroidism Multiple myeloma Pagets disease Metastatic carcinoma of the bone Prolonged immobilization Drugs –  thiazide diuretics – reabsorpion of Ca  Excess Vit D , IV Ca Dr Anurag Yadav
  • 30. Symptoms Nausea, Vomiting Confusion, depression Osteoporosis Renal stones Ectopic calcification & pancreatitis Blood alkaline phosphatase is elevated Dr Anurag Yadav
  • 31. Hypocalcimea  Ca < 8.8mg/dL  Ca levels <7.5 Tetany Causes  Deficiency of Vit D  Hypoparathyroidism  Medullary carcinoma of thyroid – increased Calcitonin  Decreased absorption  Renal failure – increased phosphorus levels  Hypoalbuminemia Dr Anurag Yadav
  • 32. Symptoms  Neuromascular irritability  Muscle cramps  Seizures  Bradycardia  Prolonged QT Interval Tetany  Carpopedal spasm  Laryngismus & stridor  Chvostek’s sign +ve  Trousseu’s sign +ve Dr Anurag Yadav
  • 34.  Hypocalcemia can be treated by  Oral calcium with vitamin D supplementation  Underlying cause should be treated.  Tetany needs IV calcium (usually 10 mL 10% calcium gluconate over 10 minutes, followed by slow IV infusion. IV calcium should be given only very slowly. Dr Anurag Yadav
  • 36. OSTEOPOROSIS  After the age of 40–45, calcium absorption is reduced and calcium excretion is increased  there is a net negative balance for calcium. This is reflected in demineralization.  After the age of 60, osteoporosis is seen.  reduced bone strength and an increased risk of Fractures is seen in patients.  Decreased absorption of vitamin D and reduced levels of androgens/estrogens in old age are the causative factors. Dr Anurag Yadav
  • 37. Osteopetrosis  It is otherwise called marble bone disease. There is increased bone density.  It is due to mutation in gene encoding carbonic anhydrase type II.  The deficiency of the enzyme in osteoclasts leads to inability of bone resorption. Paget’s Disease  Localized disease of bone characterized by osteoclastic bone resorption followed by disordered replacement of bone. It is common in people above 40 and may affect one or several bones. Familial incidence is also reported.  Bone markers are useful in monitoring response to treatment using bisphosphonates. Dr Anurag Yadav
  • 38. Renal Osteodystrophy  Secondary hyperparathyroidism as a consequence of persistent hypocalcemia causes high turnover bone disease, osteitis fibrosa.  Osteomalacia may result (low bone turnover) due to defective synthesis of 1,25 DHCC Dr Anurag Yadav
  • 39. MARKERS OF BONE DISEASE  Metabolic bone diseases result from an imbalance between bone resorption and bone formation.  Osteopenia is more common than excess bone formation. Dr Anurag Yadav
  • 40. GENERAL MARKERS OF BONE DISEASE  Serum Calcium,  Serum Inorganic Phosphorus,  Serum Magnesium And  Urinary Excretion Of Calcium And Phosphorus,  Total Alkaline Phosphatase And Total Acid Phosphatase Levels.  These are the routine tests of bone metabolism.  Vitamin D nutrition should be determined by measuring serum 25-hydroxy vitamin D.  PTH measurement would be required if serum calcium is abnormal. Dr Anurag Yadav
  • 41. Markers of bone resorption Markers of bone formation Telopeptide •Serum carboxy terminal telopeptide of type I collagen •N-telopeptide of type I collagen Serum bone specific isoenzyme of alkaline phosphatase (sBAP) Pyridinium cross links derived from collagen Serum osteocalcin (s-OC) Tartrate resistant acid phosphatase (TRAP) Serum midportion of osteocalcin (sm-OC) Urinary hydroxyproline excretion Procollagen type 1 peptidase Serum intact osteocalcin (s-OC) Serum amino-terminal propeptide of type I collagen (PINP) Dr Anurag Yadav
  • 42. Dr Anurag Yadav MBBS, MD Assistant Professor Department of Biochemistry Instagram page –biochem365 Email: dranurag.y.m@gmail.com