DEPARTMENT OF PROSTHODONTICS AND CROWN AND BRIDGE

SIBAR INSTITUTE OF DENTAL SCIENCES,

TAKKELLAPADU, GUNTUR-9

A SEMINAR ON
CALCIUM METABOLISM

PRESENTED BY GUIDED BY
G.VINEELA Dr. ANNE GOPINADH, MDS
I YEAR PG STUDENT PROFESSOR & HOD
BATCH 2016-19
 Calcium metabolism

CONTENTS

 Introduction
 Distribution of Calcium
 Functions of Calcium
 Sources of Calcium
 Recommended Dietary Allowances
 Calcium turnover
 Absorption of Calcium
 Excretion of calcium
 Calcium Balance
 Calcium Homeostasis
 Disorders of calcium metabolism
 Calcium and Teeth
 Conclusion
 References

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 Calcium metabolism

INTRODUCTION

During the course of evolution, when life began to evolve on land, organisms had
to be equipped with structures that would provide support. Ultimately internal skeletons
evolved which required mechanisms for accumulating and storing calcium in solid form
extracellular. At the same time mechanisms had to be evolved to keep the calcium
concentration of blood and body fluids varying erratically.

Calcium is the most abundant of the minerals in the body, constituting about 2% of
the body weight. Although 99% of this inorganic element is found in the skeletal system,
structural support is not the only function. A small fraction of about 1% of calcium is seen in
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 Calcium metabolism

the cells and extracellular fluids which serves a diverse number of biologically important
functions, like cell signaling, muscle contraction coagulation of blood etc.
Calcium metabolism is the distribution and utilization of calcium throughout the
body. It can be viewed as a series of interactive compartments all communicating with each
other and providing feed back information. This includes gastrointestinal intake and output,
renal excretion, hormone regulation, bone storage and a circulatory compartment, which
integrates the remaining compartments.

DISTRIBUTION OF CALCIUM

-Before the 5th month of intrauterine life very little calcium is found in the fetus as bone
formation starts only by the seventh month of intrauterine life.
-The body of the infant at birth contains about 27.5 grams of calcium and calcium
continuously gets deposited in the bone during the growth of the body.
-The total calcium content in
a 1 year old child - 100g
a 70 kg adult -1000-1500g

-About 99% of the total calcium is present in bones and teeth and the remaining 1% in
blood and body fluids as well as the intracellular compartments.
TOTAL CALCIUM
-The calcium concentration is more
(1-1.5 kg) in the extracellular fluids than in the intracellular fluids
1%
-At the cellular
99% level, the calcium within the cell is concentrated in fixed binding sites such
BONES EXTRACELLULAR INTRACELLULAR
as the mitochondria, endoplasmic reticulum,
FLUIDS ribosome etc
MOSTLYHence more than 99% of the calcium within the cell is present in the
Ca-PHOSPPHATES
PARTLY Ca-CARBOANTES
cellular organelles as compared to cytoplasm. CYTOPLASM
BLOOD
ORGANELLES
PLASMA 9-11mg/dl

DIFFUSIBLE
NON-DIFFUSIBLE FORM 6mg/dl
FORM 4mg/dl

DISTRIBUTION OF CALCIUM IN THE BODY

BOUND TO OMPLEXED TO
PLASMA Ca2+ ANIONS-Citrates
PROTEINS IONIZED FORM Phosphates
3mg/dl 1mg/dl carbonates
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ALBUMIN GLOBULIN
3mg/dl 1mg/dl
 Calcium metabolism

BO

FUNCTIONS OF CALCIUM

1) CELL SIGNALLING
Calcium acts as a second messenger in some hormonal actions

2) NEURAL TRANSMISSION
Calcium regulates the excitability of nerve fibres, nerve centers and neuromuscular system

3) MUSCLE CONTRACTION
Calcium increases the interaction between actin and myosin.
4) BLOOD COAGULATION
5) ENZYMATIC CO-FACTOR
Calcium is needed for activation of enzymes like pancreatic lipase, ATPase
etc
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 Calcium metabolism

6) MEMBRANE INTEGRITY AND PERMEABILITY

7) CYTOSKELETAL FUNCTIONS
Calcium regulates the microtubules and microfilament mediated processes.
8) SECRETION
9) BIOMINERALIZATION
Calcium is needed for the formation and development of bones and teeth.

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 Calcium metabolism

SOURCES OF CALCIUM
DIET CALCIUM CONTENT (mg/100g)
CHEESE 800
CREAM 50
MILK 120
NUTS 13-250
DRIED PULSES 40-200
ROOTS VEGETABLES 20-100
GREEN VEGETABLES 25-250
EGGS 56
BUTTER 15
OATMEAL 55
WHITE BREAD 100
FISH 20-120
MEAT 14
MAIZE 12
RICE 6
POTATOES 8
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 Calcium metabolism

2) CALCIUM SUPPLEMENT

In the form of calcium carbonate, calcium gluconate or calcium lactate

tablets,syrups.
Eg. CALCINOVA TABLETS - Chewable calcium 500mg
CALCIUM SANDOZ - Chewable calcium 500 mg
SHELCAL KID –TABLETS - elemental calcium 250 mg
TRICAL –D SYRUP

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 Calcium metabolism

RECOMMENDED DAIRY DIETARY ALLOWANCES FOR CALCIUM

CATEGORY AGE CALCIUM(mg)

INFANTS Upto 6 months 360
6 months – l year 640
CHILDREN 1-3 Years 800
4-6 Years 800
7-10 Years 800

MALES 11-14 Years 1200

AND 15-18 Years 1200
FEMALES 19-22 Years 800
23-50 Years 800
51+ 800

PREGNANCY + 400
LACTATION + 400
(as recommended by the Food and Nutrition Board, of the U.S. National
Research Council)

2) As recommended by the National Institute of Health (1994):-

-Children 1- 10 Years = 800 mg –1200 mg
-Young adults 11 – 24 years }
- Pregnant and lactating women} = 200 –1500 mg
- Men 25 – 65 Years}
Women 25 - 50 Years} = 1000 mg
Women taking HRT (51 - 65 Years}
- Women not taking
- HRT (51 – 65 Years}
Both Men & (25 - 50 Years} = 1500 mg
Women > 65 Years}

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 Calcium metabolism

CALCIUM TURNOVER
Bone
Intracellular fluid
13,000mg
Diet Exchange
100mg/day 4000mg

Repaid exchange
Absorption
350mg/day 20,000mg/day
Gastro
intestinal Stable
tract Extracellular fluid Accretion 1,000,000mg
Secretion 1300 mg
250mg/day 300mg/day

Reabsorption
300mg/day

Filtration 9980 mg/day

Feces
900mg/day Kidneys

Urine 100mgday

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 Calcium metabolism

ABSORPTION OF CALCIUM

Calcium absorption from the GIT chiefly depends upon

1) presence of calcitriol (Vit D3)
2) need of calcium in the body

EXOGENOUS CALCIUM ENDOGENOUS CALCIUM

(from diet) (from gastrointestinal secretions)

Ca in
Gastrointestinal
Lumen

Absorption in
Intestine

TRANSCELLULAR PARACELLULAR
PROCESS PROCESS

- Active process - Passive process

- in duodenum - throughout the intestine
the intestine
upper jejunum

- When Ca intake is low - when Ca intake is high

- Vitamin D dependent - Vitamin D independent

CELLULAR MECHANISM OF ASBORPTION

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ENTRY INTRACELLUAR EXTRUSION

DIFFUSION FROM CELL

1) Entry of calcium into cells

-by Calcium channels
2) Transport within cells
- by Calcium carrier proteins
calbindin – in intestinal cells
calmodulin – in most cells
- Vesicles
3) Extrusion from cells
(i) an active process
- utilizing Calcium ATP ase pump
Ca2+ – Na+ antiporter
(ii) Exocytosis

FACTORS AFFECTING CALCIUM ABSORPTION

PROMOTING FACTORS INHIBITING FACTORS

1. VITAMIN D 1. PHYTATES AND OXALATES
Induce synthesis of Ca binding - from insoluble salts
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 Calcium metabolism

Proteins in intestinal cells.

2. PARATHYROID HORMONE
↑ synthesis of calcitrol
3. ACIDITY (10w pH)`
Ca2+ becomes soluble
4. BILE SALTS
Hydrophilic action on Ca2+
5. LACTOSE
6. AMINO ACIDS – LYSINE,
ARGININE (i.e. PROTEIN
INTAKE)
7. LOW DIETARY CALCIUM
8. EXERCISE
9. SUN LIGHT
2. HIGH DIETARY PHOSPHATE
3. INCREASED FREE FATTY
ACIDS
(in malabsorption syndromes)
4. Alkaline conditions (high PH)
5. HIGH CONTENT OF DIETARY
FIBRE
6. INCREASED DIETARY
CALCIUM
7. INTESTINAL DISEASES
8. ANTACIDS
9. OLD AGE

EXCRETION OF CALCIUM
This occurs through STOOL
URINE
SWEAT
LACTATION

1. EXCRETION OF CALCIUM THROUGH STOOL

Calcium in the feces comes from two sources

1) UNABSORBED EXOGENOUS (FOOD) CALCIUM (major portion)
2) ENDOGENOUS CALCIUM
Secreted into the intestine by way of bile and other digestive secretions
In humans, the amount of endogenous calcium is approximately equal to the
urinary output
When absorption is high, there is a tendency for endogenous calcium to be low.
Of a dietary intake of 1000 mg of calcium 800 – 900 mg is excreted in feces.
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 Calcium metabolism

-
2. EXCRETION OF CALCIUM THROUGH SWEAT

A daily loss of about 15 mg of calcium occurs via perspiration and increases with increases
sweating.

3) EXCRETION OF CALCIUM THROUGH LACTATION

During lactation a mother loses between 150 – 300 mg of calcium daily.

4) EXCRETION OF CALCIUM THROUGH URINE

Only 55% of the total plasma calcium is available for filtration which
consists of
i. The ionized fraction - 50%
ii. Fraction complexed with anions - 5%
- Normally, 98 – 99% of the filtered calcium is reabsorbed in the kidneys.
i.e. about 1-2 % (100 mg/day) is excreted in the urine, which is equal to the net.
- amount absorbed daily by the gastro-intestinal tract.
- Calcium is excreted mainly in the form of calcium chloride and calcium phosphate.

FACTORS INFLUENCING URINARY CALCIUM EXCRETION

INCREASE EXCRETION DECREASE EXCRETION

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 Calcium metabolism

1) DECREASE IN PTH - INCREASE IN PTH

2) EXTRACELLULAR FLUID -EXTRACELLULAR FLUID
EXPANSION CONTRACTION
3) PHOSPHATE DEPLETION - PHOSPHATE EXCESS
4) METABOLIC ACIDOSIS - METABOLIC ALKALOSIS

1) PARATHYROID HORMONE (PTH)

- PTH exerts the most powerful control on renal Ca2+ excretion and is responsible for
maintaining calcium homeostasis
- It acts by stimulating increased calcium absorption from the ascending limb of Henle’s
loop and the distal tubule.

2) PHOSPHATE LEVEL
Increase in increase in decrease in
Phosphate level PTH level Calcium excretion

3) CHANGES IN EXTRACELLULAR FLUID VOLUME

This alters calcium excretion mainly by affecting Na+ and fluid reabsorption
in the proximal tubule.

ECF increase in Na+ and enhances

Contraction water reabsorption Ca2+reabsorption

urinary Ca2+ excretion

CALCIUM BALANCE

1) CALCIUM EQUILIBRIUM
In a normal adult, the renal excretion of calcium ions is balanced by
gastrointestinal absorption.

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 Calcium metabolism

INTAKE OF CALCIUM = EXCRETION OF CALCIUM

2) POSITIVE CALCIUM BALANCE

During growth and pregnancy, intestinal absorption of calcium ions
exceeds urinary excretion, and these ions accumulate in newly formed fetal tissue and bone.

INTAKE OF CALCIUM > EXCRETION OF CALCIUM

3) NEGATIVE CALCIUM BALANCE

In bone diseases (eg osteoporosis) or a decline in lean body mass (eg

bedridden old patients) there is an increase in urinary calcium ion loss without a change in
intestinal absorption resulting in a net loss of calcium ions from the body.
Other conditions where a –ve calcium balance is seen.
Hyperthyroidism
Hyper parathyroidism
Rickets
Osteomalacia
Celiac disease
INTAKE OF CALCIUM < EXCRETION OF CALCIUM

PLASMA CALCIUM
The total concentration of calcium in plasma is maintained within very narrow
limits. The mean value is 10mg/100 ml (2.5 mmol/L) and the range of variation is only –11
mg/100 ml

The calcium in the plasma is present in three different forms

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1) IONIC CALCIUM
- This is the physiologically active form of calcium and is important for most functions of
calcium in the body, including its effect on the heart, on the nervous system and on bone
formation.
- It is diffusible through the capillary membrane.
- It can be filtered in the kidneys
- With rise in pH there is a fall in ionic calcium level in plasma, which causes increased
neuromuscular irritability, known as tetany.

2) PROTEIN-BOUND CALCIUM
- This accounts for 40% of the total plasma calcium levels.
- The calcium is electrostatically bound to plasma proteins.
- With increase in pH, there is an increase in this fraction of calcium due to increase in net
negative charge on the plasma proteins.
- This fraction is distributed between the plasma albumin and globulin
fraction in a ratio of 3:1
- It is non diffusible through the capillary membrane and is not filtered in the kidneys

3) NON-IONIC CALCIUM
- This forms the remaining 10% of the total plasma calcium levels
- It is present in the form of complexes with citrate ,phosphate and
bicarbonates
- It is diffusible and is filtered in the kidneys
- Plasma calcium tends to be higher in men than in women
- It decreases as the individual age
- Plasma calcium is in very rapid, dynamic equilibrium with the calcium in
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 Calcium metabolism

the extra cellular fluid

CALCIUM HOMEOSTASIS
This refers to the maintenance of normal physiological, plasma calcium levels by a
group of physiological processes involving regulation of intestinal calcium deposition and
resorption from bone and calcium excretion.

An increase or decrease in serum calcium levels by the following mechanisms

1. First line defense (rapid effect)
By the buffer function of the exchangeable calcium in bones

2.Second line defense

By hormonal control of calcium ion concentration

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 Calcium metabolism

BONE STORAGE OF CALCIUM

99%of the total body calcium is in the skeleton and forms about 2% of the body weight the
calcium in bone is of 2 types :
i. EXCHANGEABLE /LABILE CALCIUM
ii. NON EXCHANGEABLE /NON LABILE CALCIUM
LABILE CALCIUM
-This is a readily exchangeable reservoir that is always in equilibrium with the
calcium ions in the extracellular fluids
-It consists of soluble amorphous calcium phosphate compounds
-A total of 5-10gms of calcium is available for exchange ,which comprises
about 0.5-1%of the total calcium salts of the bone-It is involved in the homeostatic
regulation of plasma Ca2+.

NON LABILE STABLE CALCIUM

- This is a much larger pool of stable calcium that is only slowly exchangeable.
- It is concerned with bone remodeling by the constant interplay of bone resorption and
deposition.
- However the calcium interchange between plasma and this stable pool is only about
300mg(7.5mmol)per day.

HORMONAL REGULATION OF CALCIUM METABOLISM

The hormones involved in calcium metabolism is classified as follows:-

CALCITROPIC HORMONES
1.Parathyroid hormone (PTH)
2. Calcitonin(CT)
3. Calcitriol(1,25 Dihydroxycholecalciferol)
OTHER HORMONES
4.Parathyroid hormone- related protein (PTHrP)
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5.Growth hormone (GH)

6.Gonadal steroids
-estrogen
-androgens
7.Adrenal steroids
-glucocorticoids
8.Insulin
9.Prostaglandins
10.Growth factors
11.Cytokines
The three calcitropic hormones ,the parathyroid hormone, calcitonin and calcitriol
through their actions and interactions on bone ,kidney and the gastrointestinal tract ,act to
maintain serum(and extracellular fluid )calcium within a normal rang
PARATHYROID HORMONE (PTH)
Parathyroid hormone or Parathormone is an 84- amino acid peptide secreted by the ‘chief
cells’ of the two pairs of parathyroid glands located adjacent to the posterior aspect of the
thyroid gland in the neck.
It is first synthesized in the ribosomes as a
preprohormone(pre-pro-PTH)

Converted to PROHORMONE by the endoplasmic reticulum(pro-PTH)

And finally to the HORMONE (PTH) by the golgi apparatus.

Degraded by the secreted in increased amounts
chief cells when
when serum Ca↓
serum Ca ↑
Stored in secretory granules in the cytoplasm of the cell

PTH circulating in the

blood is broken By the
kupffer’s cells of the liver

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Excreted by glomerular
filtrationIn the kidney.
 Calcium metabolism

CALCIUM SENSING RECEPTORS (CaSR)

These are cell surface receptors which detect the concentration of extracellular
ionized calcium for which calcium is an agonist. The calcium sensing receptors are present
in
1) cells of parathyroid gland
2) thyroid C cells
3) distal nephron of the kidney
4) lacenta
5) brain
6) gastrointestinal tract.
REGULATION OF PTH BIOSYNTHESIS AND SECRETION

PTH LEVELS PTH LEVELS

1) decreased ionized I ncreased serum

serum calcium calcium

2) decreased 1,25 dihydro- increased 1,25 di-

xy Vit D3 hydroxy VitD3

3) hypomagnesemia hypermagnesemia

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 Calcium metabolism

4) increased phophate decreased phosphate

levels levels.

BIOLOGICAL EFFECTS OF PARATHYROID HORMONE

Parathormone mediates its effects through the PTH receptors found on the target cells
which when activated increase the cyclic adenosine monophosphate (cAMP) levels in these
cells.
These receptors recognize PTH as well as a similar hormone, parathyroid hormone
related protein (PTHrp) and hence designated as PTH/PTHrp receptors.

N BLOOD
PTH increases the ionized fraction of serum calcium

ON BONE

-It increases the resorption of bone which is its main action

-This occurs in two phases
i. RAPID PHASE /IMMEDIATE REACTION
ii. SLOW PHASE / LATE REACTION

RAPID PHASE
-This occurs within a few minutes to about 2 hours
-Is due to osteolytic activity
-Characterised by an increase in serum calcium level
-Involves the mobilization of amorphous bone salts from the bone fluid

SLOW PHASE
-This appears after about 12 hours and is more sustained
-Is due to osteoclastic activity
-Also involves a rise in serum calcium levels
-Involves actual bone resorption

ON KIDNEY
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 Calcium metabolism

-Decreases calcium excretion

→ by increasing the resorption of calcium in the distal nephron
-Increases phophate excretion
→ by inhibiting the resorption of phosphate in the renal proximal tubule.

ON GASTROINTESTINAL TRACT

Increases calcium resorption

→ by a weak direct effect
→ mostly by an indirect effect by enchancing the conversion of
25-hydroxy D3 to 1,25-dihyroxy D3
VITAMIN D (CALCITRIOL)

ACTIONS OF CALCITRIOL

1) ENHANCES ABSORPTION OF CALCIUM AND PHOSPHATE

FROM INTESTINE

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This is the main action of calcitriol, brought about by two probable

mechanisms.
i. Involving a genetic regulation
By involving the synthesis of a carrier protein for Ca2+

ii. Non genetic regulation

By promoting endocytotic capture of calcium and its transport across duodenal
mucosal cell in vesicular form.

2)ON BONE

→ Vit D promotes mineralization of osteoid

-by providing sufficient ambient calcium
-this action is carried out at low doses of vit D(calcitriol)

→ At higher doses, calcitriol increases bone resorption

-This is done by activating osteoblasts which have vitD receptors
on their surface

Increases the production of cytokines like IL-6 from osteoblasts

IL-6 acts on osteoblasts to activate them

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 Calcium metabolism

Bone resorption

3) ON KIDNEY
Vit D receptors are also present in proximal tubules of the kidney.
1,25(OH)2D3 acts through these receptors to increase renal proximal calcium and
phosphate reabsorption .Therefore it decreases their excretion.

REGULATION OF THE SYNTHESIS OF CALCITRIOL

INCREASED CALCITRIOL DECREASE CALCITRIOL

↑ PTH ↓ PTH
↓Calcium levels ↑ Calcium levels
↓ Phosphate levels ↑Phosphate levels

↑1,25(OH)2D3
CALCITONIN

-Calcitonin is the hypocalcemic hormone produced by parafollicular ‘C’ cells of thyroid .It
is a 32 amino acid containing polypeptite hormone with effects opposite to those of PTH
-Calcitonin secretion is controlled by serum calcium through the calcium sensing
receptor(CaSR) present on the C cells but at higher concentrations of calcium
i.e hypercalcaemia increases secretion of calcitonin
hypocalcemia inhibits secretion.

ACTIONS ON BONE
-Inhibits bone resorption
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 Calcium metabolism

→ by inactivating the calcitonin receptor rich osteoclasts.

ACTIONS ON KIDNEY
-Increases calcium and phosphate excretion
→ by inhibiting proximal tubular calcium and phosphate reabsorption.
ACTIONS ON BLOOD
-Decreases calcium
-Decreases phosphate

PARATHYROID HORMONE – RELATED PROTEIN (PTH-rp)

-This polypeptide hormone is a product of many normal and malignant tissues

-It is produced in foetal tissues and some normal adult tissues.
-It is also secreted by many types of malignant tumours like those of breast, kidney and
lung.
-It is the major humoral mediator of hypercalcemia of malignancy
-It produces hypercalcemia by activating the PTH /PTH-rp receptor.
-PTHrp is required for normal development as a regulator of the proliferation and
mineralisation of cartilage cells, as a regulator of placental calcium transport.
-Although PTH and PTHrp are produced by different genes, they have some chemical
resemblance and biologically behave alike i.e elevate serum calcium
level.
HORMONAL REGULATION OF BONE METABOLISM

DECREASE BONE RESORPTION

1) Calcitonin
2) Estrogen

INCREASE BONE RESORPTION

1) PTH
2) PTHrp
3) Glucocorticoids
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4) Thyroid hormones
5) High dose Vit D

INCREASE BONE FORMATION

1) Growth hormone
2) Vit D metabolites
3) Androgens
4) Insulin
5) Low dose PTH/PTHrp

DECREASE BONE FORMATION

1) Glucocorticoids

DISORDERS OF CALCIUM METABOLISM

This can be broadly classified as disorders resulting in
1)HYPOCALCEMIA
2)HYPERCALCEMIA

HYPOCALCEMIA
A decrease in total plasma calcium concentration below 9mg/dl in the
presence of normal plasma protein concentration

HYPERCALCEMIA
An increase in total plasma concentration of calcium above 11mg/dl

CAUSES OF HYPOCALCEMIA
1 2. 3.

INCREASED HYPOPARATHYROIDISM VITAMIN D

PHOSPHATE DEFICIENCY
LEVELS

CHRONIC RENAL SURGICAL(Common) OSTEOMALACIA

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FAILURE(Common THYROIDECTOMY RICKETS

PARATHYROIDECTOMY VIT D RESISTANCE

PHOSPHATE CONGENITAL DEFICIENCY

THERAPY
(Di George sydrome)
IDIOPATHIC
HYPOPARATHYROIDISM
SEVERE
HYPOMAGNESEMIA

6)MISCELLANEOUS 5) DRUGS 4) RESISTANCE

ACUTE CALCITONIN TO PTH
PANCREATITIS BISPHOSPHONATES PSEUDOHYPO
CITRATED BLOOD PARATHYROIDISM
IN MASSIVE
TRANSFUSION
LOW PLASMA
ALBUMIN
MALNUTRITION
CHRONIC LIVER
DISEASE
MALABSORPTION eg. Coeliac disease

SIGNS AND SYMPTOMS

The clinical manifestations of hypocalcaemia are due to disturbance in cellular membrane
potential which result in neuromuscular irritability.
-Muscle cramps involving the back and legs are common complaints
In slowly developing hypocalcemia
Mild diffuse encephalopathy
Dementia,depression,psychosis

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Cataracts
In severe hypocalcemia[ plasma Ca < 7mg/dl]
- tetany
- laryngospasm
- generalized convulsions
- arrhythmias or heart block

TETANY
Results from 1)severe hypocalcemia
2)reduction in ionized fraction of plasma Ca without marked
hypocalcemia(severe alkalosis)
Characterised by
1)paraesthesia of lips, tongue, fingers, feet
2)carpopedal spasm(Accoucher’s hand and Trousseau’s sign)
3)spasm of facial musculature(Chvostek’s sign)
4)generalized muscle aching.

CAUSES OF HYPERCALCEMIA

1 2. 3.
EXCESSIVE PTH
MALIGNANT EXCESS ACTION
SECRETION
DISEASE(second OF VITAMIN D
commonest cause)
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PRIMARY -MYELOMA IATROGENIC/SELF

HYPERPARATHYROIDISM( -SECONDARY ADMINISTERED
commonest) DEPOSITS IN BONE EXCESS
-ADENOMA (Common) PRODUCTION OF GRANULOMATOU
-TERTIARY OSTEOCLASTIC S eg
HYPERPARATHYROIDISM FACTORS BY Tuberculosis
-ECTOPIC PTH SECRETION TUMOURS Sarcoidosis
-PTH RELATED LYMPHOMA
PROTEIN
SECRETION(PTHrp)

SIGNS AND SYMPTOMS OF HYPERCALCEMIA

-Mild hypercalcemia is usually asymptomatic
-Clinical manifestations of hypercalcemia:-
constipation
anorexia
nausea and vomiting
abdominal pain
-elevation of plasma calcium>12mg/dl is associated with
-drowsiness/lethargy
-confusion ,delirium
-psychosis,coma
-prominent skeletal muscle weakness(due to neuromuscular involvement)
-hypercalciuria with nephrolithiasis leading to acute renal failure or
irreversible damage .
-cardiac arrhythmias

OSTEOPOROSIS

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Osteoporosis, an atrophy of bone, is a condition in which the rate of bone deposition is

depressed resulting in decreased bone density and a reduction in the total bone mass.The
quantity of bone is diminished but its composition is normal, unlike in osteomalacia where
there is a failure of the matrix to mineralize resulting in large amounts of osteoid tissue.
Osteoporosis can be of 2 types
1)Generalized (systemic factors)
2)Localized

GENERALISED OSTEOPOROSIS
ETIOLOGY:
- age
- endocrine abnormalities
menopause
hyperparathyroidism
diabetes mellitus
excess adrenal cortisol hormone
- hereditary
- poor nutrition(calcium deficient diets)
- drugs chemotherapeutic agents

TREATMENT:
1)ESTROGEN THERAPY

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 Calcium metabolism

Decrease bone loss and increases bone density.

2)SELECTIVE ESTROGEN RECEPTOR MODULATORS(SERM)
eg.Raloxifene
Tamoxifene
-increased bone density with reduced risk of breast cancer in post menopausal women.

3)CALCITONIN

4)BIPHOSPHATES
eg. Alendronate
decreases bone resorption by inhibiting osteoclast cells.
5)SUPPLEMENTAL CALCIUM

Osteopetrosis
It is a hereditary bone disease.Failure of osteoclastic bone resorption.Hypocalcemia is
seen.Secondary hyperparathyroidism may be seen.
Pagets disease
Increase in the alveolar width is seen.Serum Calcium and Serum Phosphorous levels
are within the limits.Serum alkaline phosphatase levels are increased.

CALCIUM METABOLISM AND TEETH

Teeth are the densest structures in the body with the highest calcium content per
unit volume.Teeth are privileged sities as far as the calcium in teeth does not
participate in the body’s calcium turnover i.e calcium from teeth cannot be mobilized
to supply the serum, when there is a serum calcium deficiency.

ROLE IN DENTINOGENESIS

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 Calcium metabolism

-One of the earliest important events for the preparation of mineralisation during hard tissue
formation is the movement of calcium and phosphate, the main constituents of the hard
tissue mineral, from the blood vessels to the extracellular region, where mineralisation takes
place

-This involves 2 pathways

1) a transcellular pathway
calcium from → odontoblasts → predentine
blood vessels

2) a direct paracellular pathway

calcium from → predentine and dentine → blood vessels

-
Calcium inflow in odontoblasts occurs through l-type calcium channels, demonstrated in
the basal plasma membrane of the odontoblast. These are voltage gated calcium uptake
channels. When these are blocked, mineralisation of the dentine is affected.

-Within the odontoblast cellular calcium ions is either freely dissociated in the cytosol
bound to calcium complexing agents or localized in intracellular compartments like
endoplasmic reticulum, golgi apparatus and mitochondria.
-Phosphoryn, a phosphoprotein has been identified in actively synthesizing odontoblasts and
in dentine particularly in the intertubular dentine. Due to its high affinity for calcium
binding protein and plays a significant role in regulating the ordered deposition of
hydroxyapatite crystals within the preformed dentinal matrix.

-Odontoblast calcium extrusion is accomplished by a Ca+-ATPase and

Ca2+/Na exchanger.

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IN AMELOGENESIS
Amelogenesis occurs in 4 stages
1) Morphogenetic stage
2) Differentiation stage
3) Secretory stage
4) Maturation stage

It is during this secretory and maturation phases that calcium ions are introduced
into forming enamel.
Ameloblasts control the influx of calcium into mineralizing enamel. The route by
which calcium moves from the blood vessels through the enamel
organ is
Intercellular - in the secretory phase
Transcellular - in the maturation phase
Presence of hypocalcemia during these stages results in enamel hypoplasia.

CONCLUSION:

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 Calcium metabolism

An adequate calcium intake throughout life is essential for maintenance of the skeleton, by
far the largest body reservoir of calcium. Appropriately high calcium levels is needed in the
first two decades, when the body calcium mass increases to near maximum. Bone
metabolism is thus closely related to calcium metabolism.
Serum and extracellular calcium concentration are closely regulated within
a narrow physiological range that is optimal for many normal cellular functions. The
calcium regulating hormones that control this homeostatic system are PTH and vitamin D,
which act at bone, kidney and gastrointestinal tract to increase serum calcium and
calcitonin, which correspondingly act to decrease serum calcium.
Any disturbance in calcium homeostasis leads to clinical symptoms of hypo- or
hypercalcemia.

REFERENCES
TEXT BOOKS

 Parathyroid hormone, calcitonin, calcium and phosphate metabolism, vitamin d, bone

and teeth In: Guyton, editor. Textbook of medical physiology, 10th edition.

 Hormonal control of calcium metabolism and the physiology of bone In: Ganong
W F, editor. review of medical physiology 17th Edition.

 Mineral metabolism in Satyanarayana text book of biochemistry 5 th edition 2007

 Sequelae of denture wearer’s, Boucher’s text book of treatment for edentulous

patients 12 th edition by Zarb and bolender

 Google search website, www.googlesearch.com.

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