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CALCIUM ANDPHOSPHATE METABOLISM

Dr Jagadish S

Dept of Pedodontics

2calcium and phosphate metabolism


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Skeleton

Introduction.

History.

Distribution.

Sources. Daily requirements.

Plasma level.

Absorption and excretion.

Functions. Homeostasis.



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Skeleton

Effects of altered calcium and

phosphate level and its effect on dental

tissue.

Calcium and phosphate in fetus.

Calcium and phosphate in neonates.

Conclusion.

References.



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Introduction

Why?

The hard tissues of the body:

Bone 50 to 60%

Cementum 45 to 50%

Dentin 60 to 70%

Enamel 90 to 96%



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Metabolism

The sum total of tissue activity as considered in termsof physicochemical changes associated with the availability

utilization and disposal of individual body constituents i.e.

Proteins, Fat, Carbohydrates, Vitamins ,Minerals Water and

the endocrine influences on these - DUNCAN

Essential elements

An element is considered essential when its deficiency

consistently results in suboptimal physiologic function that

can be prevented or reversed by supplementation with

physiologic levels of the element - MERTZ



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CLASSIFICATION OF MINERALS

MACROMINERALS: Dailyrequirements >100mg

Na, K, Cl, Ca, P, Mg and S

MICROMINERALS: Dailyrequirements


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History

The word calcium originates from the Latin word

Calcis meaning lime.

It was discovered by sirHumpheryDavy(1808).

It is a silvery alkaline earth metal.. 3.5% of

earths crust.



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Distribution

Serum 9 11mg/dlC.S.F 4.5 - 5mg/dlMuscle 70mg/dlNerve 15mg/dl

Total calcium:1100-1200g (1.5%of the body weight)

99%in bonesand teeth

1% in softtissue and

ECF

0.9% is seenin soft tissue

0.1% is seenin

ECF



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Calcium in plasma andinterstitial fluid

The normal concentration of plasma calcium:

9 11 mg/dl (4.5 5.5 mEq/L)

Three forms ofCalcium:

Ionized Calcium

Non ionized Calcium and

Protein bound



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Sources

Milk good source

Egg, fish and vegetables medium sources

Cereals small amount.

Daily requirement

Adult 800mg/day

Infants (


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Absorption of calcium

Vit D

Acidic pH

Organic acids, lactose andbasicA.A

Increase in protein

Ca and phosphorus ratio of1:1

Absorption increased by



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Phytic ci

Ox l tes

Ste torrhoe

Ol ge(55 60yrs)

High phosphate content .

Absorption of calcium

Absorption ecrease by

14calcium an

phosphate metabolism


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Excretion of calcium

Feces

Urine

Sweat

10-15%

10-15% 70-80%



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Functions of calcium

Formation and development of bones and teeth

Blood coagulation

Transmission of nerve impulse

Secretion of hormones

Mediates excitation and contraction of muscle fibers

Activation of enzymes through calmodulin

Maintains the integrity of intracellular substances.



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Effects of increased Calcium

Depression of the nervous system

Sluggishness ofreflex activities

Lack of appetite

Constipation

Reduced ST segment and QT intervals in ECG

Osteitis fibrosa cystica

Deposition of crystals(kidney tubules, alveoli of

lungs, wall of arteries).18calcium and phosphate metabolism


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Etiologies ofHypercalcaemia

Increased GI Absorption

Increased Loss From Bone

Increased bone turnover

Decreased Bone Mineralization

Decreased Urinary Excretion



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Effects ofreduced Calcium

Neuromuscularhyperexcitability(hypocalcaemictetany


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Etiologies ofHypocalcemia

Decreased Bone Resorption:

Low PTH

Vitamin D deficiency

Osteoblastic metastases

Decreased GI Absorption:

Poor dietary intake of

calcium

Impaired absorption of

calcium

VitaminD

deficiency Decreased conversion of vit

D to calcitriol.



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Etiologies ofHypocalcemia

Increased Urinary Excretion:

Low PTH

Thyroidectomy

Autoimmune hypoparathyroidism




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Etiology of Enamel hypoplasia

Astudy was conducted to determine the causes of

enamel hypoplasia and interglobular dentine.

They have concluded that enamel hypoplasia is due to

hypocalcaemia

Formation of interglobular dentine is due to

hypophosphtaemia.

Etiology of Enamel Hypoplasia:AUnifying Concept, JPediatr 98:888-893. NIKIFORUK,G. and FRASER, D.(1981)

calcium and phosphate metabolism 23


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Regulation of blood Calcium level

Regulated mainly by three hormones:

Parathyroid hormone

1,25-dihydroxy cholecalciferol

Calcitonin



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Parathyroid Hormone

Pre-pro PTH (115 amino acids)

Pro-PTH (90 amino acids)

PTH (84 amino acids)

Enzymatic deletion of 25 amino acidsEnzymatic deletion of 25 amino acids

Enzymatic deletion of6 amino acidsEnzymatic deletion of6 amino acids

E.R of chiefcells

Golgi

apparatus



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PTH

Osteolysis Loss ofCalcium

Osteoclastic bone resorption Loss ofCalcium & Phosphate

DCT Calcium reabsorption

PCT Inhibit Phosphatereabsorption

Stimulates hydoxylation of25HCC to 1,25-DHCC

1,25-DHCC

Intestinal Calciumabsorption



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Stimulation for PTH secretion

Low level ofCalcium in plasma.

Maximum secretion occurs when plasma

Calcium level falls below7mg/dl.

When plasma Calcium level increases to

11mg/dl PTH secretion.

This is an exception as Calcium influx into

endocrine cells stimulates hormonal secretion.



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Action on bone



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PTH modulates osteoblast and ostoclastactivity.

Osteoblasts produce the protein OPG

(osteoprotegerin) which binds osteoclast

rank-L receptors and down regulates

osteoclast production and maturation.

PTH decreases OPG p

roduction, allowing the

protein rank-L produced byosteoblasts, to

bind the rank-L receptors on osteoclast.



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Hyperparathyroidism



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the Impact of Primary Hyperparathyroidismon the Oral Cavity

They concluded that HPT are more likely to have:

Mandibular tori

Widening of PDL space

Loss of lamina dura

Reduced cortical bone thickness at the angle of mandible.

The Journal ofClinical Endocrinology & Metabolism , doi:10.1210/jc.2005-2282Allan D. Padbury,



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Hyperparathyroidism



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oral manifestations of secondary

hyperparathyroidism related to long term

hemodialysis therapy: fletcher et al.

Patients on long term hemodialysis therapy may

develop secondar

y hyper

par

athyr

oidsm with or

alsymptoms.



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Oral manifestations


Spaced dentition

Thining of cortical boneLoss of lamina dura


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Hypoparathyroidism

Decreased level of PTH Due to

Surgical removal of parathyroid gland

Congenital absence of the gland

Atrophy of the gland

Effects:

Decreased plasma calcium levelIncreased plasma phosphate level



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Clinical signs & symptoms

Hyperactive reflexive

Spontaneous muscular contractions

Convulsions

Laryngeal spasm

Dental findings

Delayed eruption

Hypoplasia of enamel

External root resorption and

Root dileceration.



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Activation of vit D and its Effect


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Vitamin D Calcium & Phosphate

absor

ption

Weak

action

Calciumreabsorption

Bonereso

rption

Plasmacalcium &

Phosphate levels



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Dental findings in Rickets

Developmental anomalies ofenamel and dentin

Delayed eruption

Malallignment of teeth

Increase caries index

Wide p

redentine zone and mo

re

interglobular dentin



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Renal Rickets

Renal tubular acidosis

Deficient hydrogen ion production

Loss of bicarbonates, sodium,

pottasium, calcium, magnesium and

phosphate.

Bone changes are similar to rickets.



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Osteomalacia & Osteoporosis



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Tetany :

Condition when plasma calcium level falls below6mg/dl.Hyper excitability of nervous system.

Causes peripheral muscle spasm.

Clinical signs Chvosteks sign

Contraction of ipsilateral facial muscles when tapping

facial nerve over the angle of the mandible.

Erbs sign

Hyperexcitability of muscles to electrical stimulation



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Trousseaus sign(carpopedal spasm)

Spasm of the muscles of the upper extremitycausing flexion of wrist and thumb and

extension of fingers.

Clinically can be produced by applying

pressure with sphygmomanometer cuff on the

upper arm.45calcium and phosphate metabolism


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Calcitonin and its action



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OTHERHORMONES AFFECTINGCALCIUM METABOLISM

GROWTHHORMONE

INSULIN

TESTOSTERONE

ESTROGENPLACENTALLACTOGEN

THYROIDHORMONE



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Other factors:

Plasma proteins

50% of calcium are non diffusible form bound

to proteins.

Plasma phosphate

Areciprocal relation exists between calcium

and phosphate.



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Integrated Hormonal Regulation

Calcium Deficiency

Hypocalcaemia

PTH

urinary phosphateexcretion

plasma phosphatelevel

(Hypophosphatemia)1,25-DHCC

Intestinal calciumabsorption

plasma calcium level

(Normal)

osteocytic &

osteoclastic boneresorption

Renal calciumabsorption

Calcitonin secretion

Normal level

If excessive

Negative feedback- PTH

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Phosphate Metabolism

History

1st metal isolated by electrolysis sirHumphrey

Davy(1807).

Soft silvery-white alkali metal.

2.5% of earths crust.

7th most abundant element on earth.



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Phosphorus


Total phosphate:500-800 gms

Normal plasma levels:

2.5-4.5 mg/dl

bonesand teeth

soft tissues

Organic Inorganic

(0.5-1mg/dl)(Adults:3-4mg/dl)

(children:5-6mg/dl)within cells

ECF, bloodand otherfluids

52

S f Ph h


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Sources of Phosphorus

Occurs together with calciumProtein-rich foods such as milk,

cheese, meats, poultry, and fish.

Cereals, legumes, nuts, soft drinks

Milk Phosphoprotiens

Brain, Liver, Egg yolk PhospholipidMuscles Phosphogen & ATP



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Phosphorus: Requirements


Age in years Estimated averagereqiurements

< 1 year 100-275 mg

1-3 years 380 mg

4-8 years 450 mg

9-18 years 1055 mg

19-70 years 580 mg

Dietary Reference Intakes, Food and Nutrition Board,NationalAcademy of Sciences-Institute of Medicine, 1997


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Functions of Phosphorus

Formation of bones & Teeth

Production of high energy phosphate compounds

Synthesis of nucleoside co-enzymes

DNAand RNAsynthesis

Formation of phosphate esters

Activation of enzymes by phosphorylation

Phosphate buffer system in blood and saliva.



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THE PHOSPHORUS OF SALIVA, WITH SPECIAL REFERENCE

TODENTAL CARIE

GUY E.YOUNGBURG ET AL: J DENT RESEARCH

In phosphate content, the average saliva of persons having

dentalcaries is not appreciably different from normals.

Average values for inorganic phosphorus are: normals 17.50

mg.,dental caries 18.13 mg of phosphorus per100 cc. of

saliva.

There is no reason to believe that the phosphorus of the

saliva plays anyrole in dental caries.



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Phosphate absorption

Factors favoring

Low calcium diet

Vitamin D

PTH

High phosphate diet

Factors decreasingHigh calcium diet

Vitamin

Ddeficiency

Antacids-Al(OH)3

Growth ho

rmone

During lactation.


Phosphate


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calcium and phosphate metabolism

Phosphateregulation

H h h t i


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Hyperphosphatemia

Serum phosphorus level >5 mg/dL.

The pathophysiology of hyperphosphatemia

involves decreased Ca++ due to increased

serum phosphorus.

Elevated serum phosphorus levels are

associated with the progression of kidney

disease.

27% greaterrisk of mortality.



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Hyperphosphatemia

Causes:

Increased intake

Increased release from cells

Increased release from bone

Decreased exc

retion


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Effects ofHyperphosphatemia

Phosphate trapping

Respiratory insufficiency

Erythrocyte dysfunction

Nervous Dysfunction

Leukocyte Dysfunction

Metabolic acidosis



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Hypophosphataemia

Causes:

Decreased Intake

Increased cell uptake

Increased Excretion Familial hypophosphatemia

Chronic alcoholism & Diabetic Ketoacidosis

Primary hyperparathyroidism

Vit D deficiency

Metabolic acidosis


ff f h h i


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Effects ofHypophosphataemia

Interferes with renal tubularreabsorption ofCa, PO4,K & H2O

Leads to rickets & Osteomalacia

Severe case is a life threatening condition & can cause

hemolysis, muscular weakness, mental changes, decreased

myocardial contractility & respiratory failure

Deformities of bone & teeth.

Hypocalcified dentin, abnormal Cementum, alveolar bone

pattern & highly placed pulp horns reaching up to DEJ are seen.



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Bone and its relation to extracellularcalcium and phosphate

Composed of30% organic matrix and 70% of

salts.

Bone salts are principally of calcium and

phosphate i.e hydroxyapatite.

Ca/p ratio ------- 1.3 to 2.



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Exchangeable calcium

Bone contains exchangaeble ca, that is always in

equilibrium with the ca ions in the extracellular

fluids

Small portion of this is seen in liver and GIT also

0.4- 1 % of the total bone ca

Provides rapid buffering mechanism



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Calcium and phosphate in fetus

About 22.5 gm of ca and 13.5gms of p is

accumulated in fetus during gestation

The bones are relatively unossified and have mainly

a cartilagenous matrix

X ray films will not show any ossifications untill

about the 4th month of pregnancy.


Need for Calcium and Phosphates


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Need forCalcium and Phosphatesin neonates

Neonate is in stage ofrapid ossification of its bone

at birth

Ready supply of ca and p throughout infancy is

needed

Supplied ordinarily by the usual diet of milk

Calcium absorption byGIT requires vit D

Hence vit D deficiency in infants can develop

severe rickets in only a few weeks.



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Conclusion68calcium and phosphate metabolism

f


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References

GuytonAC, Hall JE: Human Physiology andMechanisms of Disease, 6th edition.

Rhoades RA, TannerGA:Medical Physiology,2nd edition.

DavidsonsPrinciples and Practice of Medicine

19th

edition.


f


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Referances

Structures of Biological Minerals in DentalResearch

Journal of Research of the National Institute of

Standards and Technology

David B Ferguson Oral Bioscience

ShaferTextbook ofOral Pathology 5th edition.

Robbins pathologic basis of disease.



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