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Calcium homeostasis refers to the regulation of the concentration of calcium ions in the extracellular fluid [Ca++]ECF.
Calcium Homeostasis
Bone CaCa++ ++ 99%99% PO4PO4¯ ¯ 85%85% (1-2Kg/ body wt.) ( 1 Kg/ body wt.)(1-2Kg/ body wt.) ( 1 Kg/ body wt.)
↓↓Major source ofMajor source of
Serum CaSerum Ca++++ & Phosphate & Phosphate
↓↓ Free ionized CaFree ionized Ca++++ only only ( 50% of blood level )( 50% of blood level )
..Blood coagulationBlood coagulation..
..Normal cardiac functionNormal cardiac function....Normal skeletal m. contractionNormal skeletal m. contraction..
..Release of neurotransmittersRelease of neurotransmitters..
Bone MassBone Mass
↓ ↓ ContinuousContinuous Remodeling →Bone building. →Bone building.
Bone lossBone loss . .
young→↑ building.young→↑ building. Old →↑ lossOld →↑ loss..
controlledcontrolled
byby
Osteoblasts Osteoclasts) ) Bone matrix forming (Bone matrix Bone matrix forming (Bone matrix
destructingdestructing cells) cellscells) cells ( (
BalanceBalance
Remodeling
Regulation of Bone-Mineral HomeostasisRegulation of Bone-Mineral Homeostasis
Hormonal Regulation
Non-hormonal Regulation
Bone MassBone Mass ↑) ↑) blood Cablood Ca++++ level level((
Bone MassBone Mass ↓) ↓) blood Cablood Ca++++ level level((
..PTHPTH....Vit. DVit. D..
..CorticosteroidsCorticosteroids..
㊉㊉ osteoclastsosteoclasts..
Θ osteoblastsosteoblasts..
..CalcitoninCalcitonin....AndrogensAndrogens....OestrogensOestrogens..
..G.HG.H....Thyroid HThyroid H..
㊉㊉ osteoblastsosteoblasts..
ΘΘ osteoclastsosteoclasts..
Bisphosphonates
Parathormone (PT) Parathormone (PT)
Release Release → → regulated by level of blood Caregulated by level of blood Ca++++ & PO4 & PO4.¯.¯ ↑ ↑ ➣ ➣when when →→ Ca Ca++++ ↓ & ↑ PO4 ↓ & ↑ PO4.¯.¯
↓Through effects onThrough effects on
Bone Kidney GIT. rate rate
of Resorptionof Resorption
. Ca Ca++++ reabsorption reabsorption... PO4¯ excretion by PO4¯ excretion by
renal tubulesrenal tubules..
Action:Action: → → Tends to Tends to Ca Ca++++ level in blood level in blood..
IndirectIndirect㊉㊉ synthesis ofsynthesis of
calcitirolcalcitirol) ) active vit. Dactive vit. D(.(.➣➣
absorptabsorptnn of Ca of Ca.++.++
Uses of PT . Uses of PT . →→ Was used for hypocalcaemia, Was used for hypocalcaemia,
( PT→ immunological agent )( PT→ immunological agent )
Treatment of hypocalcaemiaTreatment of hypocalcaemia
1-Hypocalcaemic tetany 1-Hypocalcaemic tetany
→→ Calcium gluconate I.V.Calcium gluconate I.V.
2-Long R/ of hypo-para-thyroidism:2-Long R/ of hypo-para-thyroidism:
→→Vitamin D + Calcium gluconate or LactateVitamin D + Calcium gluconate or Lactate
..
1-Hypocalcaemic tetany 1-Hypocalcaemic tetany
→→ Calcium gluconate I.V.Calcium gluconate I.V.
2-Long R/ of hypo-para-thyroidism:2-Long R/ of hypo-para-thyroidism:
→→Vitamin D + Calcium gluconate or LactateVitamin D + Calcium gluconate or Lactate
..
Vitamin DVitamin DSteroid HormoneSteroid Hormone Vit.D2Vit.D2-Ergocalciferol-Ergocalciferol..
Vit.D3Vit.D3-Cholecalciferol-Cholecalciferol..Human) Pro D3=7 dehydrocholestrol(
↓UVR
Vit.D3 (Chole-calciferol)
KidneyKidney
25) OH(
2525))OHOH ( (Vit.DVit.D33
LiverLiver
1,251,25))OHOH((22 D D33 (Calcitriol) (Calcitriol)
) )ActiveActive((
Complete hydroxylation
Two forms:
ActionAction:: →→
↓Through effects onThrough effects on
.↑↑ resorption & Formationresorption & Formation.. (Normal→ resorption.)Normal→ resorption.) (Rickets→ formation.) Rickets→ formation.)
Bone Kidney GIT
.↑ Ca↑ Ca++++ &↑ PO4¯ &↑ PO4¯ absorption .absorption .
Tends to Tends to Ca Ca++++ & &PhosphatesPhosphates
.↑ Ca↑ Ca++++ &↑ PO4¯ &↑ PO4¯ reabsorptionreabsorption byby renal tubules.renal tubules.
Uses of vit.DUses of vit.D
..Prevention & treatment of Rickets & osteomalaciaPrevention & treatment of Rickets & osteomalacia..
..Treatment of hypoparathyroidismTreatment of hypoparathyroidism..
.Osteoporosis..Osteoporosis.
.
The boy pictured here has rickets, a disease resulting from a lack of calcium and/or vitamin D in the diet. Rickets weakens the long bones, so that they are not strong enough to support the body; they bend outwardly under the body’s weight.( the skeleletal and muscluar systems Gregory Stewart)
Radiograph of the scapula of a 58-year-old woman with osteomalacia. The presence of a pseudofracture, or Looser's zone, is indicated by an arrow.
CalcitoninFrom parafollicular (C) cells of thyroid glandsFrom parafollicular (C) cells of thyroid glands
↓↓ Hypercalcaemia & Hypercalcaemia & vitamin D vitamin D..
Action:Action: → → Tends to ↓ CaTends to ↓ Ca++++ &Phosphates &Phosphates
↓Through effects onThrough effects on
Bone Kidney
Θ Osteoclast activity.
Tends to Tends to Ca Ca++++ &Phosphates &Phosphates
as a result ofas a result of
.Θ Ca Ca++++ & PO4¯ reabsorption & PO4¯ reabsorption by renal tubules.by renal tubules.
Uses of CalcitoninUses of Calcitonin: : → → As it As it Θ bone Resorption.
Diseases in which Diseases in which active or chronic loss of bone massactive or chronic loss of bone mass::
.Post menopausal osteoporosis..Post menopausal osteoporosis. .Hypercalcaemia of malignancy..Hypercalcaemia of malignancy. .Paget’s disaese.Paget’s disaese..
PreprationsPreprations::
Human calcitoninHuman calcitonin → t½ 10 min → t½ 10 min..Calcitonin-salmonCalcitonin-salmon→ long t½ , more potent→ long t½ , more potent,,
))miacalcinmiacalcin ,( ,(s.c , I.M, nasal sprays.c , I.M, nasal spray . .
PTH Vitamin D CalcitoninPTH Vitamin D Calcitonin
Bone: Bone: ↑ resorption. ↑ resorption & ↓ resorption↑ resorption. ↑ resorption & ↓ resorption..
formationformation..
Kidney: Kidney: ↑ tubular Ca↑ tubular Ca++ ++ ↑ tubular Ca↑ tubular Ca++++&& ↓ tubular Ca↓ tubular Ca ++ ++&& reabsorption. POreabsorption. PO44¯reabsorpt¯reabsorptnn PO PO44¯ reabsorpt¯ reabsorptnn..
↑ ↑tubular POtubular PO44¯̄ excretionexcretion..
G.I.T. G.I.T. Indirect through ↑ CaIndirect through ↑ Ca++++ &PO &PO44¯̄ calcitriol reabsorptioncalcitriol reabsorption..
↑) ↑) CaCa++++&PO&PO44¯̄ reabsorptionreabsorption.(.(
SerumSerum CaCa++++
POPO44¯̄
-
Bisphosphonates
Θ Bone ResorptionBone Resorption
Non-hormonal Agents affectingNon-hormonal Agents affecting Bone-Mineral HomeostasisBone-Mineral Homeostasis
..ΘΘ Osteoclast activityOsteoclast activity ) ) by by ΘΘ osteoclast proton-pump osteoclast proton-pump , ,
so so ΘΘnn of dissolution of hydroxy of dissolution of hydroxy-- apatite; the ground substanceapatite; the ground substance
matrix of bonematrix of bone.(.(
.. ㊉㊉ osteoclst apoptosis (cell death)osteoclst apoptosis (cell death)..
.. ㊉㊉ osteoblast activityosteoblast activity..
↓. ↓.calcitriol activity (active vit.D)calcitriol activity (active vit.D)↓ → ↓ → GIT absorption of CaGIT absorption of Ca.++.++
Pharmackinetics of Bisphosphonates:
Absorption: → orally , only Absorption: → orally , only 10%10% & interfered with food & interfered with food..) ) empty stomachempty stomach((
Distribution → Bone ( 50% of the dose )Distribution → Bone ( 50% of the dose )..Excretion → RenalExcretion → Renal..
Therapeutic Uses
..Postmenopausal osteoporosisPostmenopausal osteoporosis....Paget’s diseasePaget’s disease..
..Malignancy associated with hypercalcaemiaMalignancy associated with hypercalcaemia..
PreparationsPreparations
..Alen-dronate Alen-dronate ( fosamax )( fosamax ) Orally one tab./ w Orally one tab./ w.. ) ) patient is upright with glass of waterpatient is upright with glass of water,,
to prevent oesophageal ulcerationto prevent oesophageal ulceration.(.(
..Eti-dronate. Eti-dronate. Orally & parenterallyOrally & parenterally..
..Rise-dronateRise-dronate..
Side effectsSide effects
G.I.T irritations
ContraindicationsContraindications
.Kidney diseases..Peptic ulcer.
Drugs used for treatment ofDrugs used for treatment of
osteoporosisosteoporosis
11--Bisphosphonates. Bisphosphonates. → → ΘΘ Bone resorption Bone resorption..
22--Oestrogen. Oestrogen. → ↑ Bone mass (→ ↑ Bone mass (ΘΘoseoclast activity)oseoclast activity)..
33--Vitamin D & CaVitamin D & Ca++++..
44--Calcitonin.Calcitonin.→→ΘΘ Bone resorption Bone resorption..) ) ΘΘ osteoclast activity osteoclast activity.(.(