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Pathophysiology of Calcium, Phosphate Homeostasis

Pathophysiology of Calcium, Phosphate Homeostasis

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Published by GerardLum
Pathophysiology of Calcium, Phosphate Homeostasis
Pathophysiology of Calcium, Phosphate Homeostasis

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Published by: GerardLum on Jun 07, 2010
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Pathophysiology of Calcium, Phosphate HomeostasisBone Structure Functions
Maintain,Support, Site of Muscle Attachment (Locomotion)Protectivefor Vital Organs, MarrowMetabolic(Reserve of Ions)(Especially Calcium, Phosphate)(Maintain Serum Homeostasis)
Bone StructureBone CellsMatrixOrganic Inorganic
Osteoblast Collagen (95%) Calcium, PhosphateHydroxyapatite(Ca
10
(PO
4
)
6
(OH)
2
)Osteocytes Ground Substances (5%)
 
Keratine Sulfate
 
Chondroitin SulfateOsteoclasts
AnatomyBone StructureOsteoblast (Bone Formation) Osteoclast (Bone Resorption)
3 Steps in Bone Formation Process
 
Production of ExtracellularOrganic Matrix
 
Mineralizationof Matrixto form Bone
 
RemodellingbyResorption, ReformationRelease Calcium into SystemicCirculationActively unfixes the calcium↑ Circulating CalciumLevelsBone formation actively fixescirculating calcium in its mineral form(removing it from bloodstream)
Peak Bone Mass Schematic Representation
Crossover of Formation/ Resorption occurs during 4
th
DecadeIn Osteoporosis, Accelerated Loss of Bone (↑ Resorption, ↓ Formation)
Equilibrium of Bone Tissue
Balance between
 
Osteoclastic Resorption (of existing bone)
 
Osteoblastic Formation (of new bone)3 Major Influences on Equilibrium
 
Mechanical Stress(Stimulating Osteoblastic Activity)
 
Calcium, Phosphatelevel in ECF
 
Hormones, Local Factors (Influencing Resorption, Formation)
AbnormalitiesSerum Concentration of 2 Minerals (especially Calcium)
Serum Ca2+
Abnormally Abnormally
Renal Failure MalignancyHypoparathyroidism Hyperparathyroidism
Bone
Density
Osteoporosis Paget’s DiseasOsteomalacia Osteopetrosis
Major Regulating Organ System
(Especially Parathyroid Gland, Kidney, GIT)GIT
Ca2+ Absorption Ca2+ Absorption
Malabsorptiv Vitamin D IntoxicationMilk-Alkali SyndromeKidney
Fail to ExcreteCa2+OverexcreteCa2+UnderexcretePhosphorusOverexcretePhosphorus
HypercalcemicdisordersNephrolithiasis Renal Failur Renal TubularDisorders
Body Distribution of Calcium, PhosphateCalcium Phosphate
Total Body Calcium (1kg)
 
Bone, Teeth (99%)
 
Blood, Body Fluids IntracellularCalcium (1%)Normal Plasma Calcium
 
2.2 – 2.6 mmol/LDaily Recommended Intake (Adult)
 
1000 – 1500 mgIonized Ca2+ (Biologically Active)Total Body Phosphate (700g)
 
Bones, Teeth (85%)
 
Soft Tissues (15%)
 
ECF (0.1%)Plasma Phosphate exists
 
Inorganic Phosphate Ions(HPO
42-
, H
2
PO
4-
) (Largely)
 
Bound to Proteins (10%)
 
Freely Diffusible, Equilibrium withIntracellular, Bone Phosphate(Remainder)Recommended Phosphate Intake(Adult) – 700 mg
Distribution of Calcium in BodyInfants, Young Children
 ↑ Phosphate (influence of GH,↑ Skeletal Growth Rate)
Neonates1.2 – 2.8mmol/L< 7 y/o1.3 – 1.8mmol/L< 15 y/o0.8 – 1.3mmol/LAdults0.6 – 1.25mmol/L
Importance
 
Constituent of Cell Membranes(affect permeability, electrical)
 
↓ Ca2+ in ECF
o
 
↑ Permeability
o
 
↑ Excitability of Cell Membrane
(↓ Ca2+ in ECF - ↑ Excitability of Nerve Tissue,Stimulate Muscle Contraction)(Ca2+ - Coupling Factor between Excitation,Contraction of Actomyosin)
 
Influence CardiacContractility, Automaticity(via Slow Ca2+ channels in Heart)
 
Release of Preformed Hormones inEndocrine Cells, Release of ACh atNeuromuscular Junctions
 
MOA of Hormones within Cells(cyclic AMP, cAMP)intracellular messenger
 
Adhesive(Enzyme, Blood Coagulation)
Importance
 
Bones, Teeth
 
Phospholipids (cell membranes)
 
1° Anions in ICF (Metabolism oProteins, Fats, Carbohydrates)
 
Metabolic Processes (ATP)
 
Muscle, Neurologic Function,2,3-DPG in RBC
 
Maintain Acid-Base balancethrough action as Urinary Buffer(Excrete ↑ Daily Acid Load)
 jslum.com|Medicine   
 
 
Homeostasis
(Balance between Input, Output from ECF)
Ca, P Input Ca, P Output
Amount Ingested Amount Secreted into GITAmount Mobilized from Skeletal Pool Urinary ExcretionDeposition in BoneBalance of Bone Formation, Bone ResorptionCalcium, Phosphate Absorption, Excretion
3 Organs
(Calcium, Phosphate) (Supply to Blood, Remove it from Blood)Small IntestineBoneKidney
CalciumAbsorption Excretion
1° inDuodenum
 
15 – 20% Absorption
 
Duodenum > Jejunum > Ileum
 
Adaptive changes
o
 
↓ Dietary Ca2+
o
 
Age
o
 
Pregnancy
o
 
LactationDaily Filtered Load – 10gmFiltered Calcium (98%) arereabsorbed along renal tubule2 General Mechanisms
 
Active – Transcellular
 
Passive – ParacellularReabsorption(Proximal Tubule, Loop of Henle)
 
Filtered Load (70%)
 
Mostly Passive
 
Inhibited by FurosemideMechanism of GI Ca2+ Absorption
 
Active Transportacross Cell
 
TranscellularTransport
 
Endocytosis, ExocytosisCa(CaBP Complex)Distal Tubule Reabsorption
 
Filtered Load (10%)
 
Regulated
StimulatedInhibited
PTH CTVitamin DThiazides
Absorption of Ca2+ from GITPhosphate
(Pi)
Absorption Excretion
Greatest inJejunum, IleumLess in DuodenumFiltered (90%)Proximal Tubule (90% Reabsorbed)
Active Passive
H
2
PO
4-
HPO
4-
 Distal Tubule (10% Reabsorbed)Absorption is a Linear Function of Dietary Pi IntakeIntestinal Absorption in 2 Route
 
Cellular mediatedActiveTransportmechanism
 
Diffusional Flux (Paracellular Shunt Pathway)Regulation
 
Diet
 
Calcitropic Hormones
Excretion Excretion
PTH Vitamin DCTRegulation – Calcitropic HormonesIncreased Absorption
 
Vitamin D
 
PTH
 jslum.com|Medicine   
 
 
Major Mediators of Calcium, Phosphate BalanceParathyroid Hormone(PTH)Calcitriol(active form of Vit D
3
)Calcitonin
Role
 
StimulateRenalReabsorption of Ca2+ 
 
InhibitRenalReabsorption of Phosphate
 
StimulateBoneResorption
 
Inhibit BoneFormation,Mineralization
 
StimulateCalcitriolSynthesisStimulates GIAbsorption of bothCalcium, PhosphateExact role UnknownDoes not seem to beinvolved in homeostasisof Calcium, PhosphateStimulates RenalReabsorption of Calcium, PhosphateHypercalcemia of Hypermagnesemiastimulates secretionStimulates BoneResorption↓ Plasma Calcium (by ↓ Bone Resorption)Net Effect
 
↑ Serum Calcium
 
↑ Serum Phosphate↑ Reabsorptionof Calcium, Phosphorus,Magnesium 1° FunctionPrevent Hypercalcemiaafter ingestion of mealNet Effect
 
↑ Serum Calcium
 
↓ Serum PhosphateRegulation
 
↓ Serum [Ca2+](↑ PTH Secretion)
 
↑ Serum [Ca2+](↓ PTH Secretion)
Overview of Calcium-Phosphate RegulationDisruption of Homeostasis
Failure to achieve, restore homeostasis (result in death)
 
Injury
 
Illness
 
Disease
Disruption of Ca2+ Homeostasis Disruption of Phosphate Homeostasis
Hypocalcaemia HypophosphatemiaHypercalcaemia Hyperphosphatemia
 jslum.com|Medicine   

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