Calcium plays an important role in bone metabolism and other physiological processes. Approximately 99% of calcium in the body is stored in bones. The remaining 1% is found in extracellular fluid, where half is ionized and the other half is bound to proteins or anions like phosphate. Calcium is involved in cell membrane excitability, muscle contraction, hormone secretion, and blood coagulation. Bone mineralization is regulated by parathyroid hormone, calcitonin, and vitamin D which act to maintain calcium homeostasis by increasing or decreasing calcium absorption and resorption from bones. Imbalances can result in hypocalcemia, hypercalcemia, and bone diseases like rickets or osteomalacia.

1. Calcium and its significance inCalcium and its significance in
the bone metabolismthe bone metabolism

2. CALCIUMCALCIUM
 2% of body weight
 99% in bones
 1% in body fluids
 Plasma (Extracellular fluid)
 2.25 – 2.75 mmol/l
 Cell (Intracellular fluid)
 10-8
– 10-7
mol/l = 10-5
– 10-4
mmol/l

3. PLASMA CALCIUMPLASMA CALCIUM
diffusible
 48% (50%) Ca2+
ionized
 6% (10%) combined with anions (citrate,
phosphate) – non-dissociated
nondiffusible
 46% (40%) combined with plasma
proteins
 combination with proteins depends on pH
0.2 mmol/l Ca2+
on each pH unit

4. ROLE OF CALCIUMROLE OF CALCIUM
 excitability of cell membranes
 neuromuscular transmission and
muscle contraction
 releasing of transmitters from synapses
 “second messenger”
 stimulates secretory activity of
exocrine glands and releasing of
hormones
 contractility of myocard
 blood coagulation

5. PHOSPHATESPHOSPHATES
 80% bones and teeth
 10% blood and muscles
 10% different chemical complexes
 Plasma (ECF) 0.65 – 1.62 mmol/l
 Cell (ICF) 65 mmol/l (including
organic P)

6. PHOSPHATES (2)PHOSPHATES (2)
 calcium phosphate, hydroxyapatite
(bone)
 inorganic anions: HPO3
2-
, H2PO3-
 organic:DNA, phospholipids
 ATP, cAMP, creatinphosphate
molecules with metabolic
significance
 Ca, P rates of intake 1g/day

7. Bones – reservoir of calciumBones – reservoir of calcium
 99% of skeletal calcium forms stable bone (not
exchangeable with the Ca in extracellular fluid)
 1% is in the form of releasable pool of Ca
 Balance of deposition and resorption
 Osteoblasts – bone-forming cells responsible for
bone deposition
 Secrete type I collagen
 Differentiate into osteosytes
 Osteoclasts – “bone-eating” cells that resorb the
previously formed bone

8. Regulation of osteoblastsRegulation of osteoblasts
functionfunction
 Stimulation
 PTH (fast reaction - activation of calcium pump ? – pumping
Ca to ECF)
 1,25 Dihydrocholecalciferol
 IL-1
 T3, T4
 hGH, IGF-1 (insuline-like growth factor)
 PGE2 (prostaglandine)
 TNF (tumor necrosis factor)
 Estrogens ?
 Inhibition
 Corticosteroids

9. Regulation of osteoclastsRegulation of osteoclasts
functionfunction
 Stimulation
 PTH (not directly – through stimulation of
osteoblasts)
 1,25 Dihydrocholecalciferol (not directly – through
stimulation of osteoblasts)
 IL-6, IL-11
 Inhibition
 Calcitonin (directly – receptors)
 Estrogens (by inhibiting production of certain
cytokines)
 TGF-β (tranforming growth factor)
 PGE2(prostaglandine)

10. Thyroid and Parathyroid glandsThyroid and Parathyroid glands

11. Regulation of calciumRegulation of calcium
metabolismmetabolism
1. Parathyroid hormone
2. Calcitonin
3. Vitamin D

12. PARATHORMONPARATHORMON
 Parathyroid glands
 polypeptide of 84 amino acids
 stimulus for secretion – low plasma
calcium
 function – to INCREASE plasma calcium
 activation of osteoclasts – stimulates
absorption of Ca, P from bones
 decreases excretion of Ca by kidneys
 increases excretion of P by kidneys
 stimulates conversion of vitamin D to
calcitriol (vitamin D hormon) in kidneys

13. Relation - plasma CaRelation - plasma Ca2+2+
concentration x hormonesconcentration x hormones

14. CALCITONINCALCITONIN
 Parafollicular cells of thyroid gland (C-cells)
 peptide of 32 amino acids
 stimulus for secretion – high plasma calcium
(food intake – gastrin, CCK, glucagon)
 function – to DECREASE plasma calcium and
phosphates
 inhibits osteolysis – decreases absorption of Ca, P
from bones
 stimulates incorporation of Ca, P to bones
 decreases absorption of Ca, P in kidneys
 decreases the effect of PTH on bones – PTH
antagonist

15. CALCITRIOLCALCITRIOL
vitamin D hormonevitamin D hormone
 Skin: preprovitamin D (7-dehydrocholesterol
ergosterol) - UV irradiation: cholecalciferol
(D3), ergocalciferol (D2) - Liver:25-
hydroxycholecalciferol - Kidneys:1,25-
dihydroxycholecalciferol (conversion is
mediated by PTH)
 function – to INCREASE plasma calcium
 increases absorption of Ca in intestines stimulates
formation of calcium-binding protein in epithelial
cells
 promotes bone calcification and deposition
 inhibits secretion of PTH

16. CALCITRIOLCALCITRIOL
vitamin D hormone (2)vitamin D hormone (2)

17. Changes in CaChanges in Ca2+2+
plasma levelplasma level
Hypocalcemia
 Muscle tetany carpopedal spasm
 Dilatation of heart
 Increased cell membrane permeability
 Impaired blood clotting
Hypercalcemia
 Depression of nervous system, reflex activity,
 Increased heart contractility
 Formation of calcium phosphate crystalls

18. Carpopedal spasmCarpopedal spasm
From Guyton and Hall

19. Changes in PTH plasma levelChanges in PTH plasma level
Hypoparathyroidism
 Muscle tetany
Hyperparathyroidism
 Decalification of
bones
 Multiple fractures
(Osteitis fibrosa
cystica)
 Kidney stones

20. Changes in vitamine DChanges in vitamine D
plasma levelplasma level
Hypovitaminosis
 RICKETS (rachitis)– children
 OSTEOMALACIA - adults
 Attention! – Osteoporosis is decrease of bone
mass (matrix and minerals)
Hypervitaminosis
 Tissue and organs calcification
 Lost of body weight
 Kidney function failure

21. Basic functions of plasmaBasic functions of plasma
membranemembrane
1. Transport
2. Membrane potential
3. Ion channels
4. Mechanism of secretion

22. Structure of the plasmaStructure of the plasma
membranemembrane

23. Ionic composition of ICF andIonic composition of ICF and
ECFECF
Ion ECF
mmol/l
ICF
mmol/l
Nernst
equilibrium
potential
Na+
136-146 20 +53 mV
K+
3.8-5.4 150 -97 mV
Ca2+
2.05-2.65 c. 10-4
+120mV
Cl-
97-109 3 -97 mV
HCO3
-
22-26 10 -30 mV