calcium and its significance in the bone metabolism romana Šlamberová, md phd department of...
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Calcium and its significance in Calcium and its significance in the bone metabolismthe bone metabolism
Romana Šlamberová, MD PhDRomana Šlamberová, MD PhD
Department of Normal, Pathological and Clinical Department of Normal, Pathological and Clinical PhysiologyPhysiology
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
PLASMA CALCIUMPLASMA CALCIUM
diffusible 48% (50%) Ca2+ ionized 6% (10%) combined with anions (citrate,
phosphate) – non-dissociatednondiffusible 46% (40%) combined with plasma
proteins combination with proteins depends on pH
0.2 mmol/l Ca2+ on each pH unit
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
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)
PHOSPHATESPHOSPHATES (2) (2)
calcium phosphate, hydroxyapatite (bone)
inorganic anions: HPO32-, H2PO3-
organic:DNA, phospholipids ATP, cAMP, creatinphosphate
molecules with metabolic significance
Ca, P rates of intake 1g/day
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
Regulation of osteoblasts Regulation 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
Regulation of osteoclasts Regulation 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)
Bone structureBone structure
From Ganong
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Sex differencesSex differences
From Ganong
Thyroid and Thyroid and Parathyroid glandParathyroid glandss
Calcium metabolismCalcium metabolism
From Guyton and Hall
Regulation of Regulation of calciumcalcium metabolismmetabolism
1. Parathyroid hormone2. Calcitonin3. Vitamin D
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
Relation Relation - - plasma Caplasma Ca2+ 2+
concentration concentration x hormonesx hormones
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
CALCITRIOLCALCITRIOLvitamin 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
CALCITRIOLCALCITRIOLvitamin D hormonevitamin D hormone (2) (2)
Changes in CaChanges in Ca2+2+ plasma level 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 spasmCarpopedal spasm
From Guyton and Hall
Changes in PTH plasma levelChanges in PTH plasma level
Hypoparathyroidism Muscle tetany Hyperparathyroidism Decalification of
bones Multiple fractures
(Osteitis fibrosa cystica)
Kidney stones
Changes in vitamine D Changes 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
Basic functions of plasma Basic functions of plasma membranemembrane
1. Transport2. Membrane potential3. Ion channels4. Mechanism of secretion
Structure of the plasma Structure of the plasma membranemembrane
Ionic composition of ICF and Ionic composition of ICF and ECFECF
Ion ECFmmol/l
ICFmmol/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