CALCIUM METABOLISM

Dr Nilesh Kate
Dr Nilesh Katefriend in need à ESIC MEDICAL COLLEGE GULBARGA
DR NILESH KATE
MBBS,MD
ASSOCIATE PROF
ESIC MEDICAL COLLEGE, GULBARGA.
DEPT. OF PHYSIOLOGY
CALCIUM
METABOLISM
OBJECTIVES.
 Calcium, phosphorus & Magnesium
Metabolism.
 Calcium metabolism
 Phosphorus metabolism
 Magnesium metabolism.
 Bone physiology.
 Function and composition of Bone
 Structural considerations.
 Physiological considerations.
INTRODUCTION.
 Ca, P & Mg principal
elements constitute 60-
80% inorganic material.
 Imp –
 Ca & P for bones & teeth
 Ca & Mg for Neuro-
muscularexcitability.
Saturday, May 12, 2018
CALCITROPIC HORMONES.
 Parathyroid hormones, Calcitonin &
Cholecalciferol are concerned with ca, P & Mg
metabolism.
 Parathyroid hormone related protein (PTHrP) 4th
hormone acts on PTH receptors
 Other hormones – Glucocorticoids, Growth
hormones & Oestrogens.
Saturday, May 12, 2018
CALCIUM METABOLISM
PHYSIOLOGICAL AND BIOCHEMICAL
FUNCTIONS.
 Development of bone & teeth.
 Neuromuscular excitation.
 Blood coagulation.
 Membrane integrity and
plasma membrane transport.
 Mediation of intracellular
action of hormones.
 Activation of Enzymes.
 Release of hormones
& neurotransmitters.
 Calmodulin mediated
action of calcium.
 Regulation of
secretory process.
 Contact inhibition.
 Action on heart.
Saturday, May 12, 2018
CALCIUM DISTRIBUTION IN
THE BODY.
 Calcium in bones.
 Pool of stable calcium.
 Pool of readily
exchangeable calcium.
 Calcium in plasma.
(9-11 mg/dl)
 Diffusible (6 mg/dl)
 Non-diffusible.
(4mg/dl)
 Calcium balance.
 Absorption of calcium
– of daily intake of
1000 mg 35%
absorbed.
 Exchange of calcium
between bones and
extracellular fluid.
 Rapid exchange
 Slow exchange.
Saturday, May 12, 2018
EXCRETION OF CALCIUM
 Faecal excretion of
calcium
 Unabsorbed fraction 650
mg
 Absorbed in the form of
bile, Pancreatic juice,
intestinal secretions 150
mg so total 800 mg/day.
 Urinary excretion of
calcium. – 200 mg/day.
Saturday, May 12, 2018
TYPES OF CALCIUM BALANCE
 Neutral calcium
balance
 Positive calcium
balance.
 Negative calcium
balance.
Saturday, May 12, 2018
HORMONAL REGULATION OF
PLASMA CALCIUM LEVEL.
 Calcitropic hormones
 Parathyroid hormones
 Active form of vit D
 Calcitonin.
 Parathyroid hormone related protein – acts on
PTH receptors & imp for skeletal development in
Utero.
 Other hormones – Growth hormone, sex hormones
Saturday, May 12, 2018
PHOSPHORUS METABOLISM
 Physiological and
biochemical functions.
 Development of bone &
teeth.
 Structural part of
 ATP, GTP
 NAD, NADP
 Second messengers Camp, IP
 Nucleic acid – DNA,RNA
 Activation of enzymes.
 Role in carbohydrate
metabolism
 Phosphate buffer
system.
 Imp intracellular
Anions.
Saturday, May 12, 2018
DISTRIBUTION OF
PHOSPHATE IN THE BODY.
 Blood phosphate.
 Plasma levels – 3-5
mg/dl
 3 forms
 Protein bound – 10%
 Free ions – 40%
 Complexed with
cations 50%
 Bones & teeth – 80%
 Muscle & blood – 10%
 Chemical compounds
– 10%.
Saturday, May 12, 2018
PHOSPHORUS BALANCE
 Intake & absorption.
 Required - 800 mg/day
 Rich sources – milk,
cereals, leafy
vegetables, meat, eggs.
 Daily intake 1000 mg/d
 Vit D , PTH, Growth
hormone absorption.
 Cortisol & heavy metal
Saturday, May 12, 2018
EXCRETION OF PHOSPHATE
 Fecal excretion – 300
mg (30% of Ingested).
 Urinary excretion –
7000 mg filtered /day
 90% reabsorbed.
Saturday, May 12, 2018
PHOSPHORUS BALANCE
 Exchange of
phosphate between
extracellular fluid and
soft tissue.
 Exchange of
phosphate between
extracellular fluid and
bone.
Saturday, May 12, 2018
REGULATION OF SERUM
PHOSPHATE LEVELS
 Response to Hypocalcaemia is more immediate than
hypophosphatemia.
 Hypophosphatemia is compensated by reduced
urinary loss.
Saturday, May 12, 2018
MAGNESIUM METABOLISM
 Functions
 Role in bone & teeth
formation
 Co- factor several enzymes
 For proper Neuro-
muscular function.
 Required for release of
PTH in response to
Hypocalcaemia.
Saturday, May 12, 2018
MAGNESIUM METABOLISM
 Distribution of Mg in
the body.
 Total – 25 mg
 10 % in bone with Ca & P
 50% in soft tissue &
body fluids.
 Plasma level- 1.8-2.4
mg/dl
Saturday, May 12, 2018
MAGNESIUM BALANCE.
 Daily requirement – 300-500
mg
 Sources – leafy vegetables, nuts
& soyabean
 40% absorbed
 Increased by PTH
 Decreased by Ca, P & Alcohol
 Deficiency compensated by
decreased urinary excretion.
Saturday, May 12, 2018
BONE PHYSIOLOGY
 Bone – specialized
tough connective
tissue that forms
skeleton of the body.
Saturday, May 12, 2018
FUNCTIONS OF BONE
 Protective function
 Mechanical function
 Movements
 Metabolic function
 Haemopoietic
function.
Saturday, May 12, 2018
COMPOSITION OF BONE
 Bone matrix (Osteoid)
 Collagen fibres –
arranged in laminae,
parallel to each other,
 90% of bone matrix – type
1 collagen
 Rich in Glycine, Proline &
Hydroxyproline.
 Ground substances
 Formed by ECF &
proteoglycans
Saturday, May 12, 2018
COMPOSITION OF BONE
 Bone salts
 Inorganic component of
bone
 Contains mainly Ca & P
in the form of
Hydroxyappatite crystals
 It strengthen the bone
matrix.
Saturday, May 12, 2018
STRUCTURE OF BONE
 Structure of compact
bone.
 Make outer layer of most
bones
 Made up of cylindrical
osteons or Haversion system
 Osteon – several collagen
lamellae concentrically
present arounf haversion
canal which contains blood
vessel, lymph vessel & nerve.
Saturday, May 12, 2018
STRUCTURE OF BONE
 Structure of compact
bone.
 In between concentric
layers present
lacunnae contains
osteocytes.
 Haversion canals run
across long axis
connect with each
other also externally by
canals of Volkmann.
Saturday, May 12, 2018
STRUCTURE OF BONE
 Structure of trabecular or
spongy bone.
 Present inside compact bone &
makes up 20% of bone
 Made up of thin trabecule
seperated by space
 Trabeculae are covered by
connective tissue – endosteum
containing osteoblasts,
osteoclasts & osteoprogenitor
cells.
Saturday, May 12, 2018
CELLS OF BONE
 Osteoprogenitor cells
 Osteoblasts
 Osteocytes
 Osteoclasts.
 Bone lining cells.
Saturday, May 12, 2018
CELLS OF BONE
 Osteoprogenitor cells –
stem cells of
mesenchymal origin that
can proliferate and
convert themselves into
osteoblasts
 In the fetus – at sites of
bone formation
 In adults- over periosteum
& endosteum.
Saturday, May 12, 2018
CELLS OF BONE
 Osteoblasts – Bone
forming cells.
 Functions
 Role in laying down of the
organic matrix of bone
 Role in calcification.
 Role in bone resorption.
 Fate of osteoblasts.
Saturday, May 12, 2018
CELLS OF BONE
 Osteocytes – cells of mature
bones, maintain Ca between
bone & ECF.
 Osteoclasts- Bone removing
cells, giant multinucleated
cells, derived from
monocytes
 Bone lining cells- flattened
cells forming epithelium like
layer on bone surface.
Saturday, May 12, 2018
BONE GROWTH
 Ossification – Process
of bone formation.
 2 mechanisms
 Endochondral bone
formation.
 Intramembranous
bone formation.
Saturday, May 12, 2018
BONE GROWTH
 Endochondral bone
formation – first
formation of cartilagenous
model replaced by bone
 Intramembranous bone
formation – formation of
bones directly in a fibrous
membrane without
cartilagenous model.
Saturday, May 12, 2018
STEPS OF GROWTH OF LONG
BONES
 Formation of a cartilage
model
 Ossification and
calcification by
osteoblasts by at
primary center of
ossification.
 Growth in length & girth
by secondary centers of
ossification.
Saturday, May 12, 2018
BONE FORMATION
 Osteoid fromation.
 Bone matrix
mineralization.
 Initiation of
mineralization or
nucleation
 Rapid calcification
after enucleation
Saturday, May 12, 2018
BONE FORMATION
 Formation of trabecular
bone.
 Conversion of
trabecular bone to
compact bone.
Saturday, May 12, 2018
BONE RESORPTION
 Osteoclasts
 Process of bone
resorption.
 Removal of unmyelinated
osteoid layers
 Attachement of osteoclasts
 Release of proteolytic
enzymes & acids
 Digestion & dissolution of
bone.
Saturday, May 12, 2018
REGULATION OF BONE
RESORPTION
 Stimulated by PTH,
Calcitriol, EGF
(Epidermal growth
factor), PDGF,
 Its mediated through
PG, TGF-β, & IL-I
Saturday, May 12, 2018
BONE REMODELLING
 Def – process of bone
resorption followed by bone
formation
 Bone remodelling unit
 Phases of bone remodelling
cycle
 Resorption phase
 Formation phase.
Saturday, May 12, 2018
PHYSIOLOGICAL SIGNIFICANCE OF
CONTINIOUS BONE REMODELLING
 Bone adjusts its strength
according to stress
 So in athlete, soldiers
bones becomes heavy &
strong.
 Shape of bone rearranged
according to stress
 Old bone becomes
relatively weak & brittle.
Saturday, May 12, 2018
CALCIUM METABOLISM
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CALCIUM METABOLISM

  • 1. DR NILESH KATE MBBS,MD ASSOCIATE PROF ESIC MEDICAL COLLEGE, GULBARGA. DEPT. OF PHYSIOLOGY CALCIUM METABOLISM
  • 2. OBJECTIVES.  Calcium, phosphorus & Magnesium Metabolism.  Calcium metabolism  Phosphorus metabolism  Magnesium metabolism.  Bone physiology.  Function and composition of Bone  Structural considerations.  Physiological considerations.
  • 3. INTRODUCTION.  Ca, P & Mg principal elements constitute 60- 80% inorganic material.  Imp –  Ca & P for bones & teeth  Ca & Mg for Neuro- muscularexcitability. Saturday, May 12, 2018
  • 4. CALCITROPIC HORMONES.  Parathyroid hormones, Calcitonin & Cholecalciferol are concerned with ca, P & Mg metabolism.  Parathyroid hormone related protein (PTHrP) 4th hormone acts on PTH receptors  Other hormones – Glucocorticoids, Growth hormones & Oestrogens. Saturday, May 12, 2018
  • 5. CALCIUM METABOLISM PHYSIOLOGICAL AND BIOCHEMICAL FUNCTIONS.  Development of bone & teeth.  Neuromuscular excitation.  Blood coagulation.  Membrane integrity and plasma membrane transport.  Mediation of intracellular action of hormones.  Activation of Enzymes.  Release of hormones & neurotransmitters.  Calmodulin mediated action of calcium.  Regulation of secretory process.  Contact inhibition.  Action on heart. Saturday, May 12, 2018
  • 6. CALCIUM DISTRIBUTION IN THE BODY.  Calcium in bones.  Pool of stable calcium.  Pool of readily exchangeable calcium.  Calcium in plasma. (9-11 mg/dl)  Diffusible (6 mg/dl)  Non-diffusible. (4mg/dl)  Calcium balance.  Absorption of calcium – of daily intake of 1000 mg 35% absorbed.  Exchange of calcium between bones and extracellular fluid.  Rapid exchange  Slow exchange. Saturday, May 12, 2018
  • 7. EXCRETION OF CALCIUM  Faecal excretion of calcium  Unabsorbed fraction 650 mg  Absorbed in the form of bile, Pancreatic juice, intestinal secretions 150 mg so total 800 mg/day.  Urinary excretion of calcium. – 200 mg/day. Saturday, May 12, 2018
  • 8. TYPES OF CALCIUM BALANCE  Neutral calcium balance  Positive calcium balance.  Negative calcium balance. Saturday, May 12, 2018
  • 9. HORMONAL REGULATION OF PLASMA CALCIUM LEVEL.  Calcitropic hormones  Parathyroid hormones  Active form of vit D  Calcitonin.  Parathyroid hormone related protein – acts on PTH receptors & imp for skeletal development in Utero.  Other hormones – Growth hormone, sex hormones Saturday, May 12, 2018
  • 10. PHOSPHORUS METABOLISM  Physiological and biochemical functions.  Development of bone & teeth.  Structural part of  ATP, GTP  NAD, NADP  Second messengers Camp, IP  Nucleic acid – DNA,RNA  Activation of enzymes.  Role in carbohydrate metabolism  Phosphate buffer system.  Imp intracellular Anions. Saturday, May 12, 2018
  • 11. DISTRIBUTION OF PHOSPHATE IN THE BODY.  Blood phosphate.  Plasma levels – 3-5 mg/dl  3 forms  Protein bound – 10%  Free ions – 40%  Complexed with cations 50%  Bones & teeth – 80%  Muscle & blood – 10%  Chemical compounds – 10%. Saturday, May 12, 2018
  • 12. PHOSPHORUS BALANCE  Intake & absorption.  Required - 800 mg/day  Rich sources – milk, cereals, leafy vegetables, meat, eggs.  Daily intake 1000 mg/d  Vit D , PTH, Growth hormone absorption.  Cortisol & heavy metal Saturday, May 12, 2018
  • 13. EXCRETION OF PHOSPHATE  Fecal excretion – 300 mg (30% of Ingested).  Urinary excretion – 7000 mg filtered /day  90% reabsorbed. Saturday, May 12, 2018
  • 14. PHOSPHORUS BALANCE  Exchange of phosphate between extracellular fluid and soft tissue.  Exchange of phosphate between extracellular fluid and bone. Saturday, May 12, 2018
  • 15. REGULATION OF SERUM PHOSPHATE LEVELS  Response to Hypocalcaemia is more immediate than hypophosphatemia.  Hypophosphatemia is compensated by reduced urinary loss. Saturday, May 12, 2018
  • 16. MAGNESIUM METABOLISM  Functions  Role in bone & teeth formation  Co- factor several enzymes  For proper Neuro- muscular function.  Required for release of PTH in response to Hypocalcaemia. Saturday, May 12, 2018
  • 17. MAGNESIUM METABOLISM  Distribution of Mg in the body.  Total – 25 mg  10 % in bone with Ca & P  50% in soft tissue & body fluids.  Plasma level- 1.8-2.4 mg/dl Saturday, May 12, 2018
  • 18. MAGNESIUM BALANCE.  Daily requirement – 300-500 mg  Sources – leafy vegetables, nuts & soyabean  40% absorbed  Increased by PTH  Decreased by Ca, P & Alcohol  Deficiency compensated by decreased urinary excretion. Saturday, May 12, 2018
  • 19. BONE PHYSIOLOGY  Bone – specialized tough connective tissue that forms skeleton of the body. Saturday, May 12, 2018
  • 20. FUNCTIONS OF BONE  Protective function  Mechanical function  Movements  Metabolic function  Haemopoietic function. Saturday, May 12, 2018
  • 21. COMPOSITION OF BONE  Bone matrix (Osteoid)  Collagen fibres – arranged in laminae, parallel to each other,  90% of bone matrix – type 1 collagen  Rich in Glycine, Proline & Hydroxyproline.  Ground substances  Formed by ECF & proteoglycans Saturday, May 12, 2018
  • 22. COMPOSITION OF BONE  Bone salts  Inorganic component of bone  Contains mainly Ca & P in the form of Hydroxyappatite crystals  It strengthen the bone matrix. Saturday, May 12, 2018
  • 23. STRUCTURE OF BONE  Structure of compact bone.  Make outer layer of most bones  Made up of cylindrical osteons or Haversion system  Osteon – several collagen lamellae concentrically present arounf haversion canal which contains blood vessel, lymph vessel & nerve. Saturday, May 12, 2018
  • 24. STRUCTURE OF BONE  Structure of compact bone.  In between concentric layers present lacunnae contains osteocytes.  Haversion canals run across long axis connect with each other also externally by canals of Volkmann. Saturday, May 12, 2018
  • 25. STRUCTURE OF BONE  Structure of trabecular or spongy bone.  Present inside compact bone & makes up 20% of bone  Made up of thin trabecule seperated by space  Trabeculae are covered by connective tissue – endosteum containing osteoblasts, osteoclasts & osteoprogenitor cells. Saturday, May 12, 2018
  • 26. CELLS OF BONE  Osteoprogenitor cells  Osteoblasts  Osteocytes  Osteoclasts.  Bone lining cells. Saturday, May 12, 2018
  • 27. CELLS OF BONE  Osteoprogenitor cells – stem cells of mesenchymal origin that can proliferate and convert themselves into osteoblasts  In the fetus – at sites of bone formation  In adults- over periosteum & endosteum. Saturday, May 12, 2018
  • 28. CELLS OF BONE  Osteoblasts – Bone forming cells.  Functions  Role in laying down of the organic matrix of bone  Role in calcification.  Role in bone resorption.  Fate of osteoblasts. Saturday, May 12, 2018
  • 29. CELLS OF BONE  Osteocytes – cells of mature bones, maintain Ca between bone & ECF.  Osteoclasts- Bone removing cells, giant multinucleated cells, derived from monocytes  Bone lining cells- flattened cells forming epithelium like layer on bone surface. Saturday, May 12, 2018
  • 30. BONE GROWTH  Ossification – Process of bone formation.  2 mechanisms  Endochondral bone formation.  Intramembranous bone formation. Saturday, May 12, 2018
  • 31. BONE GROWTH  Endochondral bone formation – first formation of cartilagenous model replaced by bone  Intramembranous bone formation – formation of bones directly in a fibrous membrane without cartilagenous model. Saturday, May 12, 2018
  • 32. STEPS OF GROWTH OF LONG BONES  Formation of a cartilage model  Ossification and calcification by osteoblasts by at primary center of ossification.  Growth in length & girth by secondary centers of ossification. Saturday, May 12, 2018
  • 33. BONE FORMATION  Osteoid fromation.  Bone matrix mineralization.  Initiation of mineralization or nucleation  Rapid calcification after enucleation Saturday, May 12, 2018
  • 34. BONE FORMATION  Formation of trabecular bone.  Conversion of trabecular bone to compact bone. Saturday, May 12, 2018
  • 35. BONE RESORPTION  Osteoclasts  Process of bone resorption.  Removal of unmyelinated osteoid layers  Attachement of osteoclasts  Release of proteolytic enzymes & acids  Digestion & dissolution of bone. Saturday, May 12, 2018
  • 36. REGULATION OF BONE RESORPTION  Stimulated by PTH, Calcitriol, EGF (Epidermal growth factor), PDGF,  Its mediated through PG, TGF-β, & IL-I Saturday, May 12, 2018
  • 37. BONE REMODELLING  Def – process of bone resorption followed by bone formation  Bone remodelling unit  Phases of bone remodelling cycle  Resorption phase  Formation phase. Saturday, May 12, 2018
  • 38. PHYSIOLOGICAL SIGNIFICANCE OF CONTINIOUS BONE REMODELLING  Bone adjusts its strength according to stress  So in athlete, soldiers bones becomes heavy & strong.  Shape of bone rearranged according to stress  Old bone becomes relatively weak & brittle. Saturday, May 12, 2018