Download Calcium and its significance in the bone metabolism

Calcium and its significance in
the bone metabolism
Romana Šlamberová, MD PhD
Department of Normal, Pathological and Clinical
Physiology
CALCIUM

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
PLASMA 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
ROLE OF CALCIUM
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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
PHOSPHATES





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)
PHOSPHATES (2)




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calcium phosphate, hydroxyapatite
(bone)
inorganic anions: HPO32-, H2PO3organic:DNA, phospholipids
ATP, cAMP, creatinphosphate
molecules with metabolic
significance
Ca, P rates of intake 1g/day
Bones – reservoir of calcium

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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
Regulation of osteoblasts
function

Stimulation





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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
Regulation of osteoclasts
function


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)
Bone structure
Due to Copyright rules it is impossible to publish
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From Ganong
Sex differences
From Ganong
Thyroid and Parathyroid glands
Calcium metabolism
From Guyton and Hall
Regulation of calcium
metabolism
1.
2.
3.
Parathyroid hormone
Calcitonin
Vitamin D
PARATHORMON
Parathyroid glands
polypeptide of 84 amino acids
stimulus for secretion – low plasma
calcium
function – to INCREASE plasma calcium


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
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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
Relation - plasma Ca2+
concentration x hormones
CALCITONIN
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




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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
CALCITRIOL
vitamin D hormone
Skin: preprovitamin D (7-dehydrocholesterol
ergosterol) - UV irradiation: cholecalciferol
(D3), ergocalciferol (D2) - Liver:25hydroxycholecalciferol - Kidneys:1,25dihydroxycholecalciferol (conversion is
mediated by PTH)
function – to INCREASE plasma calcium
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
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increases absorption of Ca in intestines stimulates
formation of calcium-binding protein in epithelial
cells
promotes bone calcification and deposition
inhibits secretion of PTH
CALCITRIOL
vitamin D hormone (2)
Changes in Ca2+ plasma 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
Carpopedal spasm
From Guyton and Hall
Changes in PTH plasma level
Hypoparathyroidism
 Muscle tetany
Hyperparathyroidism
 Decalification of
bones
 Multiple fractures
(Osteitis fibrosa
cystica)
 Kidney stones
Changes in vitamine D
plasma 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
Basic functions of plasma
membrane
1.
2.
3.
4.
Transport
Membrane potential
Ion channels
Mechanism of secretion
Structure of the plasma
membrane
Ionic composition of ICF and
ECF
Ion
ECF
ICF
mmol/l
mmol/l
equilibrium
potential
Na+
136-146
20
+53 mV
K+
3.8-5.4
150
-97 mV
2.05-2.65
c. 10-4
+120mV
97-109
3
-97 mV
22-26
10
-30 mV
Ca2+
ClHCO3-
Nernst