calcium and phosphate metabolism-final / orthodontic courses by indian dental academy

Calcium and Phosphate metabolism

CONTENTS

Introduction

Distribution of in the body

Functions

Daily requirements

Sources

o Absorption of Ca+ PO4

o Concept of Ca balance

o Factors controlling the absorption of Ca+ PO4

o Hormonal control of Ca metabolism

o Vit. D3

o PTH

o Calcitonin

o Excretion of Ca+ PO4

Summary

1


Introduction

As dentists, it is vital for us to have a complete understanding of the general

metabolism of calcium and phosphorous as it is these minerals that help in the

formation and maintenance of the teeth and their supporting bony structure. 2 points

need to be kept in mind during the course of this discussion, (1)Ca++ metabolism is a

very complicated and controversial topic on which no definite conclusion has yet been

reached, which is acceptable by all researchers, (2) This topic deals with factors

affecting Ca++ metabolism in the body as a whole and it should not be assumed that all

these factors necessarily affect the teeth.

2


IMPORTANCE AND DISTRIBUTION OF Ca++ IN THE BODY

- The human body contains about 1kg of Ca++ of which 99% is in the skeleton and

remaining 1% in soft tissues and ECF (990gms) and (10gms).

of 990 gms in the skeleton

- 10 gms forms the readily

exchangeable Ca++ pool of bone

(MISCIBLE POOL)

- 980 gm slow exchange of

Ca++ takes place (STABLE

POOL)

10.0-10.5mg/dl

NORMAL SERUM

CALCIUMLEVEL

Remaining in

soft tissues

Diffusible/ ultrafilterable form

5.5mg/dl

Non-diffusible / protein bound form

4.5mg/dl

Ionized Ca

5.0mg/dl

Bound to PO4,

HCO3, Citrate

0.5mg/dl

Bound to albumin

4.0mg/dl

Bound to

globulin

0.5mg/dl

3

10gms


FUNCTIONS OF CALCIUM

1. Contributes to hardness of bone and is a major component of teeth.

2. Stabilises the cell membrane and their permeability.

3. Maintenance of excitability of nerve and muscles.

4. Normal skeletal and cardiac muscle contraction.

5. Helps in the neurotransmitter release.

6. Secretion of granular material from exocrine and endocrine glands.

7. Hormone release and activity – discharge of non-adrenaline in the nerve terminal

cell.

8. Synthesis of nucleic acid and protein.

9. Blood coagulation – Ca++ is required for the conversion of many inactive enzymes

in the coagulation process.

DAILY REQUIREMENTS OF CALCIUM (WHO estimate)

6 months – 2 year = 0.5-0.6 g/day

1200 mg/day

16 years to adults = 0.5-0.6g/day

Pregnancy and lactation = 1.0-2gm/day

Children = 800mg/day

SOURCES OF CALCIUM AND PHOSPHOROUS

- Milk + milk products.

- Egg.

- Meat

- Fish

- Leafy vegetables

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- Hard water

PHOSPHOROUS

DISTRIBUTION OF PHOSPHOROUS IN THE BODY

- The human body contains 500-600 gms of PO4-- out of which 85% (425g) is in the

bone.

- Remaining phosphorous is present in the liver, pancreas and brain.

- Phosphorous is essential for the formation of teeth. Normal serum PO4--level is 2.5

– 4.5 mg/dl.

Serum inorganic form Organic phosphorous

3-4 mg/dl in adults remaining in the form of phospholipids &

glycerophosphates

5-6mg/dl in children

FUNCTIONS OF PHOSPHOROUS

1. Formation of bone and teeth. It is the essential constituent of all cells.

2. Important constituent of high energy phosphate compounds like ATP,

creatine phosphate, cyclic AMP, hexose phosphate, 2-3DPG,

phospholipids, nucleotides.

3. Helps in the regulation of glycolysis.

4. Phosphorylation of lipids and sugar i.e. absorption, transportation and

metabolism.

5. Urinary buffer, which regulates urinary pH.

5


CONCEPT OF CALCIUM BALANCE

Daily Requirements Of Phosphorous = 1gm/day

This term is used to describe the amount of Ca++ either stored or lost by the body over a

specific period of time. This can be calculated by deducting the amount of Ca in the urine

from the Ca taken in the diet.

Ca in diet - Ca in fasces Ca absorbed – Ca in urine

Ca lost / gained

e.g., If 1.0gm Ca is in the diet – 0.7 gm in fasces 0.3g absorbed. 0.1g net gain 0.2g

in urine

The Ca balance values are said to change with age.

In a growing child, there is a Net gain for growing and mineralizing skeleton.

- In an aging adult, there is a Net loss as Ca from bone is lost too due to conditions

like osteoporosis. Hence, amount of Ca lost is greater than Ca in intake.

ABSORPTION OF CALCIUM AND PHOSPHOROUS

It is seen that almost all the food taken in three the diet is almost completely absorbed

in the gut whreas the amount of minerals absorbed is very negligible.

This could be due to the various factors affecting the absorption of Ca++ and PO4--.

The factors can be studied under:

Factors affecting mucosal cell Factors influencing Ca absorption in the gut

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FACTORS INFLUENCING MUCOSAL CELLS

1. Vitamin D and Ca absorption

It is seen and proven that the active form of vitamin D or 1,25 DH CC (di-hydroxy

cholecalciferol) increases the absorption of Ca in the gut, kidney and bone.

This increase in absorption of Ca is directly related to the increased concentration

of Ca binding protein produced by increasing synthesis of mRNA.

1,25 DHCC

Increases synthesis of mRNA

Increases level of Ca binding protein CBP

Increases Ca plasma level

2. Effect of dietary Ca intake and Ca need

It is seen by means of experiments that the amount of Ca STORED in the body is a

factor which influences Ca absorption.

This factor can be better understood with the help of an example. e.g., Rottenson in 1938

used 2 groups of rats for his experiment

He fed 1st group 2nd group

0.15% Ca for 4 weeks 0.8% Ca for 4 weeks

4 weeks later he observed that

Stored - 190mg Ca was stored () () 570mg Ca was stored

Thus suggesting that greater the dietary intake of Ca, greater amount of Ca is stored.

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In the 2nd stage of experiment, both groups received 0.4% Ca for 5 weeks.

0.4% Ca 0.4% CA

5 weeks 5 weeks

5 weeks later ABSORBED AMOUNT

900 mg () 600 mg ()

This suggested that the group with a low Ca store absorbed more Ca than the group with

the high Ca store. Thus, suggesting that the amount of Ca absorbed is directly dependent

on the amount of Ca present in the store. This kind of an adaptation mechanism is directly

under the control of formation of 1,25 DHCC.

3. Effect of pregnancy and growth

- During pregnancy, the amount of dietary Ca absorbed increases especially

in the later months of pregnancy. Half of the Ca absorbed during

pregnancy goes to the developing foetus and the remaining half is stored in

the mother’s skeleton as a reserve for lactation.

- 2 hormones are active during pregnancy

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PLACENTAL LACTOGEN OESTROGEN

Increases Ca absorption Acts by increasing release of PTH

which increases Ca absorption indirectly.

Hence, in later stages of pregnancy

increased PTH levels are reported.

Growth Period

- During growth of children, the growth hormone levels are high. This acts

by increasing Ca absorption and reducing amount of endogenous Ca

excretion.

Parathyroid hormone

- Is one of the main hormones controlling Ca absorption. It mainly acts by

controlling the formation of 1,25 DHCC which it active form of vit. D

which is responsible for increased Ca absorption.

CALCIUM : PHOSPHOROUS RATIO An increase in the plasma Ca level causes a

corresponding in absorption of phosphorous and vice-versa. The product of Ca and

inorganic phosphate of the blood is always constant (ratio is 2 Ca : 1 PO4).

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II FACTORS INFLUENCING AVAILABILITY OF CALCIUM IN THE GUT

1. pH of the intestine

It is seen that the acids of the gastric juices dissolve most of the

Ca salts and inorganic phosphate in the diet hence allowing greater amount of Ca

available for absorption.

In the lower part of the small intestine, the pH is said to be

more alkaline, thus causing Ca salts to undergo precipitation. Hence Ca absorption

occurs only in the upper part of the small intestine where the pH is acidic.

In patients wth achlorhydria/gastrectomy, less Ca absorption takes place.

2. Amount of dietary Ca and PO4

As discussed before, as the levels of dietary Ca and PO4 is increased, the amount

of Ca and PO4 absorbed also increases but only upto certain limit beyond which

no more absorption takes place.

This is because the active transport system in the mucosal cells can deal with only

a certain load of Ca. Once this load is exceeded, the remaining Ca is either

excreted or passively diffuses in the lower part of the gut.

This a homoestatic mechanism for preventing excessive concentration of Ca in the

blood or tissue which could have a hazardous effect.

3. Phytic acid and phytates

Are found in foods like – Oat meal

Whole wheat

Cereals

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They are considered to be anti-calcifying factors as they combine with the Ca of

the diet thereby forming insoluble salts of Ca which are not absorbable. Hence, if

these phytates are taken in a diet, where the Ca intake is low or vit. D intake is low, it

is seen that severity of the deficiency disease worsens.

The effect of phytates is said to be quantitative and can be neutralized by adding

sufficient extra Ca to the diet.

4. Effect of Oxalates

Oxalates is another substance present in certain foods like spinach and rhubarb

leaves. These oxalates precipitate significant amounts of Ca from the diet or from

the digestive juices thereby decreasing the amount of Ca available for absorption.

Hence, it may be noticed that after eating spinach, a certain roughness can be

experienced on the surface of the teeth which is due to the precipitation and

deposition of Ca oxalate crystals (Ca from the saliva) on the teeth.

5. Effect of fat

Fat combines with Ca forming insoluble Ca soaps which decreases Ca absorption

but increases the availability of phosphorous for absorption.

Fat combines with Ca and liberates PO4 for absorption. Hence, excess fats hinders

Ca absorption but favour phosphorous absorption.

6. Effects of proteins and Aminoacids

It is seen that a considerable increase in the Ca absorption occurs with a high

protein diet.

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Proteins and Amino acids effect Ca in 2 ways:

Proteins form soluble complexes thus

allowing Ca to remain in a form which is

easily absorbable

Protein metabolism leads to formation of

certain acids that encourages the removal

of Ca from the skeleton. Hence, urinary Ca

level increase with a richer protein diet

Hence a high protein diet may be

considered as a possible factor for

osteoporosis.

But under such conditions, the increased

absorption is of no value as this absorbed

phosphorous cannot be retained without

Ca. Hence the excess phosphorous is

quickly excreted.

7. Effect of carbohydrates

It is seen that certain carbohydrates like lactose create an acidic pH in the gut by

favouring growth of acid producing organisms. This acidic environment of gut

favours Ca absorption.

Contradictory studies show that an increased level of Ca is seen in the body not by

increase in Ca absorbed but by decrease in Ca excreted in urine.

8. Bile salts favours Ca and phosphorous absorption as it dissolves fats thereby allowing

greater amounts of Ca+ phosphorous to be available for absorption.

12


HORMONAL CONTROL OF CALCIUM METABOLISM

A complex set of interlocking mechanisms takes place in order to allow man to

survive major dietary Ca intake fluctuations. These mechanisms are mainly controlled by

the endocrine systems.

Three main hormones acting at 3 different sites are responsible for Ca

metabolism.

1. Vit. D3 Bone.

2. Parathormone Kidney

3. Calcitonin Intestine

1) Vit. D 3 is a steroid derivative

Vit. D3 – cutaneous synthesis – important in Ca metabolism.

Vit. D2 – Ergocalciferol

Dietary source is fish, milk and eggs.

Vit. D is also known as cholecalciferol.

Besides dietary intake, cutaneous synthesis of vit.D. is another

important source of Vit. D in the body.

Present within the inner layers of the epidermis, lies an enzyme

known as 7-dehydrocholesterol. UV Rays PRE VITAMIN D3

IN LIVER

Taken to kidney

Pre Vit. D3 IN LIVER 25, OH cholecalciferol (main circulating subs, but it is

relatively inactive as it is bound to globulin.

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Bound Binding protein (DBP) to Vit. D and taken to liver


25-OH-CC

Undergoes

Hydroxylation by

1--hydroxylase enzyme whose

formation is under the control of PTH

1,25,

Dihydroxycholecalciferol or

calcitriol (active form of

Vit. D3 which is considered

to be a horomone)

- Daily requirements of vit. D 400 I.U.

Action of Vit. D.

Vit. D. acts on the intestine, kidney and bone thereby bringing about an increase in the Ca

absorbed. The active form of vit. D which is produced in the kidney has its action on

many tissues away from the site of its production. Hence 1,25DHCC is often known as a

hormone.

Acts mainly by increasing the synthesis of mRNA which directly increases the

concentration of (CBP) Ca binding protein mainly in the tissues of the intestinal mucosa.

The CBP thereby binds with increased amount of Ca and allows increased Ca to be

absorbed.

1. Action on the intestinal

1,25 DHCC increases the synthesis of CBP in the intestinal epithelium thereby

increasing the transportation of Ca from the intestinal lumen to the epithelium.

Hence, the amount of Ca absorbed is directly proportional to the amount of CBP

present in the mucosal cells.

2. Action the kidney

1,25 DHCC increases the amount of Ca absorbed from the renal tubules.

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3. Action on the bone

Before studying the action of vit. D on the bone we must understand the term

Osteocytic Membrane System.

As we all know, the cells of the bone are the:

Osteocytes

Osteoblasts

Osteoclasts

The osteocytes / resting bone cells are present within the bone.

The osteoblasts / bone forming cells are found in the endosteum lining the bone.

The osteocytes and the osteoclasts communicate with each other via the long

cytoplasmic processes. Hence, the osteoblasts present outside the bone and

osteocytes present within the bone form a system of interconnected cells that

spread all over the bone suface.

This extensive system is known as osteocytic membrane system (OCM).

This system separates the bone from the E.C.F. Bone fluid is present between

bone and OCM).

Action

Vit. D. / 1,25 DHCC is said to mediate the pump that actively transports Ca from

within the OCM to the ECF thereby raising plasma Ca levels.

Deficiency of vit. D in the body either due to a deficient diet or due to insufficient

solar exposure results in disorders known as Rickets in younger children or

Osteomalacia in adults.

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Rickets - Delayed eruption

- Malallignment of teeth

REGULATION OR CONTROL OF SYNTHESIS OF 1,25 DHCC OR FEED BACK

MECHANISM

The synthesis of active vit. D3 or 1,25DHCC is said to be tightly and directly regulated

by the parathyroid hormone. Hence, an increase in the dietary Ca results in increased

levels of 25 (OH) CC viz., the inactive form. Any fall in the plasma Ca levels cause

release of PTH. This PTH activates enzyme 1- - hydroxylase which then converts vit.

D3 to active 1,25 DHCC.

Increases synthesis of CBP hence, there is an increase in Ca absorbed. During pregnancy,

hormones like placental lactogen and oestrogen also have an effect on 1- -hydroxylase

2) PARATHYROID HORMONE (PTH)

PTH is secreted by the parathyroid glands which acts located on the posterior surface of

the thyroid gland. They are 4 in number.

PTH acts mainly on 2 sites i.e. a) bone

b) kidney

It acts by a cAMP mechanism to increase Ca levels and decrease in organic phosphate

levels in the plasma.

a) Action on the bone Fast phase

Slow phase

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i) Fast phase

Within few minutes of injection of a large dose of PTH, the plasma Ca levels is

said to increase.

Mechanism

PTH mainly acts by increasing the permeability of osteocytic membrane system to Ca so

that Ca from the bone fluid diffuses into the osteocytes and osteoblasts from where vit. D

mediated active transport transfers the Ca from within the OMS to the ECF thereby

increasing the plasma Ca levels.

Any decrease in the concentration of Ca within the bone fluid leads to dissolution of Ca

salts from the nearby bones without affecting the bone matrix (indirectly activates

osteoclastic activity or bone resorption).

ii) Slow phase

Several days of increased PTH activity is required to demonstrate the slow

phase.

PTH acts by

Activating the bone resorbing cells /

osteoclasts

Forming new osteoclasts from the

osteoprogenitor cells

Osteoclasts are multinucleated giant cells which produces resorption of bone

surfaces in contact with them. The osteoclasts send out long finger-like-projections

17


towards the bone. These finger like projections release a. PROTEOLYTIC ENZYMES

which digests the organic matrix.

b. ACIDS like citric / lactic acid which dissolves the bone minerals.

The Ca and PO4 released are poured into the ECF.

b) Action on kidney (Ca++)

- Increases the resorption of Ca from the distal tubules ( PO4– –).

- Decreases the resorption of PO4 from PCT thereby causing phosphaturia and

hypophosphatameia.

- Increases the synthesis of 1--hydroxylase which is responsible for the active

form of Vit. D which increases Ca absorption.

REGULATION OF PTH SECRETION

The plasma Ca levels are said to have a direct influence on the PTH secretion.

Any fall in the Ca levels causes a release of the PTH which brings back the level

to normal. Similarly increase in plasma Ca level inhibits the secretion of PTH.

3.CALCITONIN

Is secreted by the parafollicular cells by the thyroid glands. Mainly acts to

maintain the integrity of the bone.

Actions

It mainly acts by decreasing the permeability of OMS to Ca thereby increasing the

amount of Ca deposited in the readily EXCHANGEABLE CALCIUM POOL OF BONE.

18


It prevents the formation of new osteoclasts from osteoprogenitor cells thereby

preventing bony resorption.

REGULATION OF SECRETION OF CALCITONIN

The release of calcitonin is regulated by the plasma calcium levels. A rise in the

plasma Ca level above 9mg% stimulates the release of calcitonin.

Hence, plasma Ca levels controls the direction of PTH and calcitonin.

In adults, role of calcitonin is very minor and normal Ca level is maintained

chiefly by PTH.

Calcitonin plays a major role in pregnancy. It protects the bones of the mother

from excessive loss of Ca as during pregnancy PTH and 1,25DHCC levels are

high.

EXCRETION OF CALCIUM AND PHOSPHOROUS

Ca is said to be excreted both in the faeces and in the urine. About 90% of the

total amount of Ca is excreted in the faeces.

Ca of the urine is excreted as calcium chloride (CaCl2) and (CaPO4) 10%

remaining.

The approximate daily turnover rates of Ca in an adult are as follows:

Intake 1000mg

Intestinal absorption 350mg

Secretion in GIT juice 250mg

Net absorption over secretion 100mg

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Loss in the faeces 100mg

Excretion in the urine 100mg

BUFFER ACTION OF PHOSPHOROUS IN BLOOD

2 varieties of phosphates are present in the blood

Alkaline Acidic

H2PO4 HPO4

Concentration is about Concentration is about

1.05m mol/lit 0.26 m mol/lit

In the plasma they are in a ratio of alkaline 4 : 1 acidic.

Where pH of extra-cellular fluid becomes more acidic there is a relative increase in

H2PO4– and HPO4

– –and the opposite happen when fluid is alkaline. The average total

quantity of inorganic phosphorous ranges between normal limits of 3-4mg/dl in adults

and 4-5mg/dl in children.

IMPAIREMENTS IN BLOOD CALCIUM

I] Hypercalcemia

Increased level of Ca in the blood.

Symptoms

- Tiredeness

- Loss of appetite.

- Nausea, vomitting.

- Constipation.

- Polyuria.

- Dehydration.

20


- Loss of muscle tone.

- Decreased excitability of muscles and nerves.

Conditions in which it occurs

- Hyperparathyroidism.

- Acute osteoporosis.

- Vit. D intoxication.

- Thyrotoxicosis.

II] Pathologic calcifications of soft tissues

3 theories have been forwarded for the mechanism of calcification

a) Nucleation theory

Ca is deposited both inside and outside the cells (in mitochondria) which later

coalesce together to form calcified tissues.

This proposes that organic matrix components facilitate precipitation by acting as

heterogenous nucleating agents like collagen, phospholipids which act on specific

phosphorylating sites.

b) Booster theory

This theory proposes the existence of a mechanism to boost the local Ca and PO4

ion product to a point where precipitation occurs.

c) Matrix vesicles

Small round vesicular extracellular matrix vesicles about 100nm in diameter are

involved in the initiation of calcification. They are probably arrived from cell

processes originating from the plasma membrane.

21


i) Dystrophic calcification

- Precipitation of Ca in degenerating and dead tissues occur.

- Common sites are - Blood vessels

- Kidneys

ii) Metastatic calcification

- Due to excess Ca in the circulating blood, they are deposited in previously

undamaged tissue

- Usually occurs in – Hyper vitaminosis D

Hyperparathyroidism

Destructive lesions of the bones.

- Common sites are - Blood vessels

- Kidney

iii) Calcinosis

- Is calcification occurring in / under skin and can be associated with scleroderma.

III] Hypocalcemia

- Decreased levels of Ca in the blood (below 4mg is lethal).

Symptoms

- Tetany (Carpopedal spasm).

a) Chvotek’s sign

- Contraction of ipsilateral facial muscles elicited by tapping over the facial nerve at

the angle of the jaw.

22


b) Trosseau sign

- Spasms of the muscles of the upper extremity that causes flexion of wrists and

thumb and extension of fingers.

- This is elicited by occluding the circulation of fingers for a few minutes.

c) Erbs sign

- Is hyperexcitability of muscles to electrical stimulation.

- This occurs in cases of – - Insufficient Ca in the diet.

- Hypoparathyroidism.

- Insufficient vit. D in the diet.

- Increase in calcitonin levels.

IV. VIT D. DEFICIENCY

Ca++ level

Rickets Osteomalacia

- In children.

- Mainly affected the long bones in

the body, ribs.

- Occurs due to failure in

mineralization, due to lack of Ca level,

the cartilaginous form of bone is said to

persist.

- In adults.

- Mainly affects the flat bones in the

body.

- Especially seen in post and

menopausal women who have a

decreased dietary Ca intake and

decreased exposure to the sun resulting

in increased removal of Ca from the

bone causing softening of the skeleton

and its distortion.

23


- The cartilage continuous to grow

and proliferate thus resulting in

localized areas of cartilage proliferation

(rickety rosary, beaded bone formation)

- The weight of the body on the

uncalcified long bones result in the

bowing of legs – knock kness.

-

Dental

- Development of abnormality in

enamel and dentin.

- Delayed eruption of teeth.

- Mal-alignment of teeth.

- Higher caries index.

- Wider predentine zone.

- Increased amount of inter-globular

dentin.

Dental Findings

- Severe periodontitis

Treatment: Treatment:

Supply adequate amount of Ca and

phosphate in diet and administration of

large amounts of Vit. D.

24


V. PARATHYROID HORMONE

a) Hyperparathyroidism

- Increases levels of PTH due to an adenoma of the parathyroid glands.

C/F:

- Pathologic fracture of bones due to increased mobilization of Ca from bone

resulting in osteitis fibrosa cystica.

- Large punched out cystic area of bone.

o Joint stiffness.

o Urinary tract stones.

o Muscle weakness.

o Thirst.

o Polyuria

o Anorexia.

o Weight loss.

Dental findings

- Malocclusion seen due to definite drifting of teeth causing spacing (this occurs as

a result of increased loss of Ca from the bone, there is an absolute attempt to new

bone formation and repair resulting in spacing).

Radiographically

- Areas of radiolucency seen in bone.

- Loss of lamina dura present.

25


Treatment

- Removal of cause.

b) Hypoparathyroidism

- Seen to develop due to excision of the parathyroid glands.

- This is characterized by a fall in the serum Ca levels and an increase in the serum

inorganic phosphate levels.

C/F:

- Similar to hypocalcemia.

- Tingling and numbness in the fingers, face and toes.

- Extreme cases – cramps in the hands and feel which is very painful.

- Carpopedal spasm.

- Spasm of muscles of respiration resulting in the dread of suffocation.

- Signs of tetany present.

- In infants, symptoms of tetany may be confused for epilepsy, though there is no

loss of consciousness.

Dental Findings

- Aplasia / hypoplasia of teeth seen when hypoparathyroidism develops before teeth

formation.

c) Parathyroid poisoning

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- In rare cases, the PO4 level of body fluids rise rapidly when the kidneys cannot

excrete rapidly. Ca and PO4 get supersaturated and lead to metastatic deposition in

lungs, alveoli, kidneys, thyroid gland, gastric mucosa etc.

- Elevation of blood Ca levels before 17 mg/dl along with concurrent elevation of

PO4– – death can occur in few days.

Osteoporosis

- In adults (old age) due to decreased bone matrix rather than poor bone

calcification.

Summary

Ca and PO4 are important minerals that are required in minimal amounts for basic

activities in the body like the normal ionic Ca levels in the plasma is required for proper

bone mineralization and maintenance of cell membrane integrity. The plasma Ca levels

need to be regulated within a very narrow range because of its marked effect on

neuromuscular and cardiac excitability.

Three hormones which are – PTH

- Calcitonin

- Vit. D

Play important role in maintaining Ca and PO4 levels to a normal.

27


References and Suggested Reading

1. The Physiology and Biochemistry of Mouth – Jenkins

2. Applied Physiology – Sampson Wright

3. Textbook of Medical Physiology – Sheerwood

4. Review of Medical Physiology – Ganong

5. Physiology- Bern & Levy

6. Textbook of Medical Physiology- Guyton Hall

7. Textbook of Internal Medicine – Harrisson

8. Textbook of Medicine – Davidson

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calcium and phosphate metabolism-final / orthodontic courses by indian dental academy

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