Calcium and its significance in Calcium and its significance in the bone metabolismthe bone metabolism

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)

Thyroid and Thyroid and Parathyroid glandParathyroid glandss

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 levelHypocalcemia 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