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DEPARTMENT OF CONSERVATIVE DENTISTRY AND ENDODONTICS

COLLEGE OF DENTAL SCIENCES,


DAVANGERE.

SEMINAR ON
CALCIUM METABOLISM

Presented by :
Dr.
Dr Manju Koshy

CALCIUM METABOLISM
CONTENTS

INTRODUCTION
DISTRIBUTION OF CALCIUM IN THE BODY

BONE

BLOOD

LYMPH, CSF, AQUEOUS HUMOUR

MUSCLES

ORAL CAVITY ENAMEL, SALIVA


SOURCE, ABSORPTION, EXCRETION
CALCIUM BALANCE
FUNCTIONS OF CALCIUM IN THE BODY

BONE RIGIDITY

ECF CALCIUM CLOTTING OF BLOOD

ICF CALCIUM MUSCLE CONTRACTION


VASOSPASM OF SMOOTH MUSCLES
NEUROTRANSMISSION
FACTORS AFFECTING THE CALCIUM LEVEL IN BODY
1) PARATHYROID HORMONE
EFFECTS ON BONE
EFFECTS ON KIDNEY
EFFECTS ON INTESTINE
REGULATION OF PTH SECRETION
2) VITAMIN D
EFFECTS ON GIT
EFFECTS ON BONE
EFFECTS ON KIDNEY
3) CALCITONIN BONE
REGULATION OF BLOOD CALCIUM LEVEL
DISORDERS OF CALCIUM METABOLISM

HYPOPARATHYROIDISM

HYPERPARATHYROIDISM
PRIMARY HYPERPARATHYROIDISM
SECONDARY HYPERPARATHYROIDISM
TERTIARY HYPERPARATHYROIDISM
ECTOPIC - PTI SYNDROME

HYPOCALCEMIA
HYPERCALCEMIA
VITAMIN D DEFICIENCY
RICKETS
OSTEOMALACIA

OSTEOPOROSIS

HETEROTOPIC CALCIFICATION

DYSTROPHIC CALCIFICATION

METASTATIC CALCIFICATION

CALCINOSIS IN PULP
REFERENCES
CONCLUSION

CALCIUM METABOLISM
INTRODUCTION :
Calcium is a very important mineral in our body. It provides rigidity to bones,
muscle contraction, affects permeability of cells, blood clotting mechanism etc.
Metabolism of calcium is intimately associated with parathyroid hormone, calcitonin
and vitamin D. Importance of studying calcium metabolism has increased because : (i)
In old people, one of the major curses happens to be osteoporosis which can
cause fracture of bones.
(ii)
Calcium play vital roles in contraction of heart as well as skeletal muscles and
smooth muscles. Therefore drugs affecting calcium ion metabolism can be
used to treat hypertension or cardiac contractility.
DISTRIBUTION :
An average sized man has about 1 Kg of calcium in his body. About 99% of
this calcium is in the bone and teeth. The remaining is distributed in different tissues
as follows ;
Muscles : 8 mg per 100 gm of fresh muscle.
Plasma or serum : 9-11 mg per 100 ml of blood
RBC : Minute traces
Lymph and aqueous humour : Slightly less than plasma.
CSF : 5.3 mg per 100 ml.
Enamel ; 96% inorganic content Hydroxyapatite crystals
Dentin : 65% inorganic content
Cementum : 45-50% inorganic content
Saliva : Minute traces.
BONE CALCIUM :
Since bone constitutes the main repository for calcium, it plays a vital part in
calcium metabolism and any upsets in calcium balance can cause severe bone disease.
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Calcium in the bone mostly is in the form of calcium phosphate and partly as
calcium carbonate.
The osteoid tissue of bone is manufactured by osteoblasts and after
maturation, this osteoid undergoes mineralization with the deposition of calcium salts
in the form of Hydroxyapatite.
The bone has 2 major functions :
i)
Mechanical
- Supporting the body weight
- Providing surfaces for muscle attachment
- Protecting vital organs from trauma Eg. Skull protecting brain, Ribcage
protecting the heart, lungs etc.
ii)
Buffer : Prevents wide fluctuations of serum calcium concentration.
The ionic calcium level in the serum must remain within narrow range. If
there is fall of calcium serum, bone releases calcium.
If serum calcium level is high, calcium from serum is deposited in the bone.
All these occur under the influence of hormones mainly PTH, Vitamin D
(Calcitriol), other hormones like estrogen, calcitonin and chemicals like interleukins
(IL).
SERUM CALCIUM :
The normal serum calcium concentration is between 9-11 mg/100 ml of blood.
It exists in 3 forms :
i)
Ionized calcium : This is the active form and constitutes about 50% of the
serum calcium (4.5 mg/100 ml).
ii)
Protein bound calcium : Bound mostly to albumin, therefore it is nondiffusible (4 mg/100 ml).
iii)
Non- ionized, diffusible calcium : Smallest fraction and is present for the most
part as citrate.
In clinical practice, we only measure the concentration of serum calcium and not of
the whole blood because ;
1) Intracellular i.e. inside the RBC Concentration of calcium is very low.
2) All clinical information can be obtained by estimating calcium serum instead of
measuring that of the whole blood.
In clinical view : It is only the ionic calcium which matters as they are active.
Therefore : a) In severe hypoprotinemia of blood : Protein bound calcium falls, ionic calcium
does not fall. Therefore total serum calcium concentration is low, but still no
tetany develops.
b) In alkalosis (eg. After severe hyperventilation) the protein bound calcium
increases, but ionic calcium decreases.
Therefore total serum calcium

concentration remains unchanged but signs and symptoms of hypocalcemia


develops.
Lymph Calcium : Lymph has a lower protein content, therefore contains less calcium
than blood. CSF Ca 5.3 mg per 100 ml. Has only traces of proteins. Almost whole of
CSF Ca is in diffusible active form. Calcium of CSF fluid is constant.
SOURCES :
Milk and milk products are excellent sources of food calcium. Other sources
include water, especially hard water, eggs, cheese and green vegetables. Fish and
meat are poor sources.
DAILY REQUIREMENTS :
The Food and Nutrition Board of the National Academy of Sciences, National
Research Council, recommends daily dietary calcium intake : For newborn infants
: 360 mg/day
For children and adults
: 800 mg/day
Adolescents and pregnant
: 1200 mg/day
women and lactating women
ABSORPTION :
a) Site of Absorption :
Absorption of calcium occurs mainly from upper jejunum and duodenum.
The absorption is by : i)
A carrier mediated mechanism
ii)
Passive diffusion
i) Carrier mediated mechanism:
The carrier molecule resides in the brush border of the jejunal mucosa. A
derivative of Vitamin D 1, 25 DHCC (Calcitriol) facilitates this carrier mediated
transport.
ii) Passive Diffusion :
Small amount of calcium is also absorbed via passive diffusion i.e. molecules
move according to a chemical gradient i.e. from a solution of higher concentration
towards a solution of lower concentration.
b) Form of Absorption :

Soluble inorganic forms are much better absorbed.

Thus the organic calcium of food is converted into inorganic form before it
can be absorbed.

Insoluble calcium compounds are never absorbed. Therefore presence of


phytic acid in cereals produces formation of Caphytate which is insoluble.

Caphosphates are not absorbed.


c) Factors Affecting Calcium Absorption :
1) Vitamin D : Increases absorption of calcium from the intestine.
2) Parathyroid hormone : Increases calcium absorption

3) Thyroid : Increase calcium absorption


4) Calcitonin : Decreases calcium absorption
5) Steroid hormones : Decreases calcium absorption.
Glucocorticosteroids retard calcium absorption from GIT. Earlier, glucocorticosteorid
therapy was given for rheumatoid arthritis resulted in osteoporosis and fracture.
6) Fats (in normal amount) : Increases calcium absorption.
But when fats lost through excretion eg. Steatorrhea Calcium is lost through
faeces as Ca soaps.
7) Bile salts : Increases calcium absorption by their hydrotropic action on calcium
soaps.
8) High protein diet : Increases calcium absorption.
Proteins digested into amino acids
Aminoacids + Calcium Forms soluble calcium compounds.
9) High Phosphorous content in diet : Decreases calcium absorption because it forms
insoluble Caphosphate which cannot be absorbed.
10) pH : If pH is decreased i.e. acidic Increased calcium absorption because
calcium salts become soluble in acid medium.
If pH is increased i.e. alkaline Insoluble calcium salts therefore decreased
calcium absorption.
Lactose increases acidity due to its conversion into lactic acid Therefore
increased calcium absorption.
Oxalic acid : Insoluble Caoxalate Therefore decreased calcium absorption.
Spinach contains sufficient oxalic acid Therefore decreased calcium
absorption.
Phytic Acid : Commonly present in cereals precipitates calcium in the bowel as
insoluble Caphytate. Therefore decreases its absorption. But many vegetables
contain phytase which nullifies the inhibitory action of phytic acid.
Hydrochloric acid : Increased calcium absorption. Therefore in cases of
hypochlorhydria or achlorhydria Decreased calcium absorption.
11) Sex hormones Eg. Oestrogen and androgen. Increased calcium absorption.
Women during menopause suffer from negative calcium balance i.e. less calcium
is absorbed from blood.
Excretion :
a) Through the faeces
b) Through urine
a) Faeces : with an ordinary diet, the calcium content in human faeces is about 200
mg daily. This is believed to be totally exogenous (i.e. unabsorbed calcium).
b) Urine : About 150-200 mg are excreted through urine mainly in form of calcium
chloride and calcium phosphate. The renal threshold for calcium is approximately
7 mg /100 ml of serum calcium.
Role of Kidney in Calcium Excretion :

4) Diffusible calcium is filterable while protein bound calcium is not. 99% of


calcium is reabsorbed mostly in the proximal convoluted tubule and little
in the distal part of the nephron.
5) The renal reasborption of calcium in the distal nephron is dependent on
PTH.
CALCIUM BALANCE :
In the adult, the calcium intake and loss are same. This is called calcium
balance.
- When the intake exceeds the excretion, the person is in positive calcium balance.
- Here calcium deposition in bone is occurring.
- Seen in cases of during growth, pregnancy, lactation, acromegaly etc.
- When the intake is less than excretion, the person is in negative (-ve) calcium
balance.
- Here there is rarefaction of bones Osteoporosis.
- Seen in cases of rickets, osteomalacia, calcium deficiency, hyperactivity of
thyroid and parathyroid etc.
FUNCTIONS OF CALCIUM :
1) Bone : Bone rigidity
2) ECF : Clotting of blood
3) ICF : Muscle contraction Skeletal, Cardiac
Vasospasm of smooth muscle
Neurotransmission
1) Bone :
Calcium metabolism in bone has two divisions :
Bone remodeling
Calcium homeostasis
a) Bone Remodeling :
- Calcium gives strength to bones.
- Throughout life, small portions of bone are removed and replaced by new bone
deposition.
- For bone remodeling A set of locally acting chemicals like interleukins,
prostaglandins, estrogen and other hormones are necessary.
- Calcium acts as second messenger for initiation of formation of bone cells namely
osteoclasts and osteoblasts which are responsible for bone remodeling.
Eg. In orthodontic tooth movement.
- When a force is applied onto a tooth, it results in bone deformation and
compression of the periodontal ligament.
- This leads to the release of some extracellular signaling molecules called FIRST
MESSENGERS which include PTH, PG (Chem mediator), VIP (Vasoactive
Intestine Polypeptide).

These bind to receptors present on cell surface of target cells and initiate a process
of intra cellular signaling leads to formation of second messengers which include
cyclic AMP, cyclic GMP and calcium.
These 2nd Messengers initiate formation of bone cells namely osteoclasts and
osteoblasts which are responsible for bone remodeling.
BONE REMODELLING
Force

Bone deformation

st
1 Messengers (PTH, PG, VIP)

2nd Messengers (for cellular permeability)


+ Cyclic AMP, cyclic GAMP, Ca.
Osteoblasts and ostoeclasts

remodeling

Bone Remodeling
Bone resorption

Bone deposition

: Bone resorption and bone deposition.


: By osteoclasts
(multinucleated giant cells)
Ruffled border
(produce acids) Citric acid, lactic acid & H+
ions
Decalcification
(Protease E)
Degradation of matrix
: Osteoblasts
Osteoid matrix
Calcification

Bone remodeling is a necessity as it keeps the bone in proper physiological


state (neither excessive nor too little). Defective bone remodeling can lead to
osteoporosis, brittleness of bone, refusal to unite the fractured bone ends etc.
b) Calcium homeostasis :
Bone mobilizes calcium ion from itself to restore calcium level of serum when it
falls. Calcium deposition occurs in the bone when serum calcium level becomes
high.
2) Clotting of Blood :
Clotting of blood is an important hemostatic mechanism because the clot formed :
1) Prevents further bleeding.
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2) Seals the wound against further infection.


Normally blood contains 2 sets of materials :
1) Procoagulants Help in clotting.
2) Inhibitors (anticoagulants) of coagulation Oppose the clotting. Eg. Heparin
present in mast cells.
Normally, the effect of the inhibitors dominate but after a cutting injury, at the local
site, the effects of pro-coagulants dominate.
Mechanism of Coagulation :
Fibrinogen is present in blood and it has to be converted to fibrin for blood
clot formation. For this conversion factor Xa is necessary.
Factor Xa can be produced by any of the 2 paths.
- Intrinsic path
- Extrinsic path
Intrinsic Path : Injury of blood vessels leading to contact of Factor XII with blood
vessel.
Extrinsic Path : Injury of vascular and other cells causing release of tissue
thromboplastin also called tissue factor.
INTRINSIC
Surface contact

XII

XIIa

XI

XIa

IX

IXa
Ca

++

Ca++
VIII
Phospholipid
X

Xa

Ca++ Phospholipid
V
(II) Prothrombin
Thrombin (IIa)

XIII
XIIIa

Fibrinogen
Fibrin
Stabilized fibrin

EXTRINSIC
Tissue Damage
Tissue Factor
X

Xa

Va
VIII

II

IIa
I

VIIIa
Ia

XIIIa
Stable Fibrin
3) Muscle contraction :
For muscle contraction myosin filament should get attached with actin
muscle filament for this calcium ions are required.
Action potential on Sarcolemma
Ca2+ Channels open up
Ca release (from ECF to ICF)
AP
T Tubule
Ap to Cistern
Ca Release

Normally, in relaxed state, actin filament is covered by tropomyosin which


prevents contact of myosin with actin.
Tropomyosin covers the active sites of actin filament which are supposed to
bidn with the heads of myosin.
Calcium released after AP, binds with troponin and thus tropomysin moves
away.

Sites for myosin becomes uncovered myosin gets attached with active head of
actin Cross bridges are formed muscle contraction.
Excitation Contraction Coupling :

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AP leads to Contraction
AP excitation
electric phenomenon
Calcium coupling agents
Contraction
Mechanical phenomena
Calcium acts as coupling agent between AP and contraction.
FACTORS AFFECTING THE CALCIUM LEVEL IN BODY :
1) Parathormone : Parathormone is secreted by the chief cells of the parathyroid
glands. It is a protein in nature.
Actions of PTH :
The primary function of parathormone is to maintain the blood calcium level
within the critical range of 9 to 11 mg%.
1) It increases the blood calcium level by mobilizing calcium from bone bone
resorption.
2) It decreases the excretion of calcium through the kidneys.
3) It increases absorption of calcium from GIT.
4) It facilitates the conversion of vitamin D into its final product Calcitriol 1, 25
DHCC which causes increase absorption of calcium from GIT.
Effects on the Bone :
Bone resorption causes Increased calcium in blood
Resorption of calcium from bones occurs in 2 phases.
- Rapid phase
- Slow phase
Rapid Phase :
- Occurs within minutes after the release of parathyormone from parathyroid
glands.
- Immediately after reaching the bone, the parathormone gets attached with the
receptors on the cell membrane of osteoblasts and osteocytes.
- Osteocytic activity
- The hormone receptor complex increases the permeability of the membranes of
these cells for calcium ions.
- This increases the calcium pump mechanism allowing calcium ions to diffuse
from these cells into the plasma.
Slow Phase :
- By activation of ostoeclasts Osteoclastic activity
- Proteolytic enzymes, citric acid and lactic acid are released from these cells.
- The organic matrix of bone is dissolved, thus releasing the calcium ions which
diffuses into plasma.
- PTH causes calcium resorption and phosphate absorption from bones.
Effects on the Kidneys :
- PTH increases the reasborption of calcium from the renal tubules.
- It increases the excretion of phosphates from renal tubules.

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Effects on GIT :
- PTH increases absorption of calcium from GIT
- This is due to formation of 1, 25 DHCC from Vitamin D by kidney.
- PTH increases the absorption of phosphate ion
- For absorption of calcium from GIT, Vitamin D is necessary. For activation of
Vitamin D, PTH is necessary.
Regulation of PTH Secretion :
A) Negative feed back
Chief cells produce PTH and there are 2 substances which exert a negative
feed back effect on the production of PTH.
1) Serum calcium level : Higher the serum calcium level, lower is the production of
PTH and viceversa. Chief cells have calcium receptor in their membrane.
2) Calcitriol : Vitamin D is converted into calcitriol by PTH. High calcitriol level
inhibits PTH production and viceversa.
B) Other Regulators :
Plasma phosphates and magnesium levels can also affect the PTH production.
VITAMIN D :
Vitamin D was discovered in 1910 by McCollum.
Source of Vitamin D :
1) From 7 dehydrocholesterol present naturally in the skin.
2) Food sources like fish liver oils, particularly fish liver oils of sea fishes, milk, egg
etc.
3) Medicinal Vitamin D
Vitamin D
- Vitamin D2 : From plant sterols
- Vitamin D3 : 7 Dehydrocholesterol, fish liver oils, milk,
egg etc.
Daily Requirements :
For grown up males : Who are exposed to sunshine, may require no dietary
supplement of Vitamin D.
Pregnant, lactating women, infants, persons confined within indoor, old persons may
require Vitamin D supplements.
Chapati flour contains much phytic acid and may hinder Vitamin D absorption.
Daily supplement of 400 IU (International unit) is recommended.
Multivitamins sold in India may contain 1000 IU causing dangers of
hypervitaminosis D Hypercalcemia.
Cholecalciferol is converted into 25, hydroxycholecalciferol in liver. This process is
limited and can be inhibited by 25 HCC itself by feedback mechanism.
This inhibition is essential for 2 reasons :
a) Regulation of the amount of active vitamin D.
b) Storage of Vitamin D for months together. This is because, if Vitamin D 3 is
converted into 25 hydroxycholecalciferol, it remains in the body only 2 to 5 days.
Whereas, Vitamin D3 can be stored in the liver for months together.

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Role of Calcium Ion in Regulating 1, 25 DHCC :


If calcium increase in blood, it inhibits the formation of 1, 25 DHCC. The
mechanism involved in the inhibition of formation of 1, 25 DHCC is as follows : a) Increase in calcium ion concentration, directly suppresses the conversion of 25
HCC into 1, 25 DHCC (mild effect).
b) Increase in calcium ion concentration Decreases PTH secretion which
suppresses the conversion of 25 HCC into 1, 25 DHCC.
This regulates the calcium ion concentration of plasma itself i.e. if the PTH synthesis
is inhibited, the conversion of 25 HCC into 1, 25 DHCC is also inhibited. Lack of
this in turn, decreases the absorption of calcium ions from the intestine, from the
bones and from the renal tubules as well. This makes the calcium level in the plasma
to fall back to normal.
Functions of Vitamin D :
a) On GIT : Calcitirol increases the absorption of calcium and phosphate from the
lumen of intestine. One possible mechanism of increased calcium absorption is :
Calcitriol has receptors in the cytosol of intestinal epithelium, calcitriol binds with its
receptor this leads to formation of calbindin within these cells calbindin
facilitates transport of calcium from GIT to blood.
b) On Bone :
Vitamin D deficiency: Demineralization of bone.
Therefore conclusion : Vitamin D causes deposition of calcium phosphate in the bone.
However, the real picture is ;
Direct effect of calcitriol on bone is resorption of bone. But, so much calcium and
phosphate are absorbed by the help of vitamin D from the GIT.
Mechanism of Bone Resorption by Calcitriol :
1) Calcitriol receptors are present in the osteoblasts but not in the mature osteoclasts.
Calcitriol by acting on immature osteoclasts cause increase in number and thus
increased activity of mature osteoclasts. Increased osteoclastic activity causes
bone resorption.
2) Calcitriol by acting on osteoblasts causes release of ILs (Interluekine) from
osteoblasts ILs by acting on osteoclasts, increase the ostoeclastic activity.
3) Kidney : Vitamin D rather calcitriol, increases the absorption of both calcium and
phosphate from the renal tubules.
CALCITONIN :
- Is secreted by the parafollicular or C cells of the thyroid.
- Is a single chain polypeptide hormone containing 32 AA.
- Its effects are opposite to those of PTH.
i)
It inhibits osteoclastic activity Bone resorption is therefore inhibited.
ii)
Promotes calcium deposition in bone
iii)
Lowers serum calcium level.
REGULATION OF CALCITONIN LEVEL :
High calcium serum stimulates secretion of calcitonin and vice-versa. I.e. feed
back mechanism for controlling the plasma calcium ion concentration, works in a way

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opposite to that of parathyroid hormone system. There are two major differences
between the calcitonin and parathyroid feed back systems. First the calcitonin
mechanisms operates more rapidly, reaching peak activity in less than 1 hour, in
contrast to the 3 to 4 hours required for peak activity to be attained after the onset of
parathyroid secretion. The second difference is that the calcitonin mechanism acts
only weakly and only as a short term regulator to calcium ion concentration because it
is rapidly overridden by the much more powerful parathyroid control mechanism.
Also, the calcitonin receptors on the osteoclasts seem to down regulate within minutes
to hours in response to a calcitonin stimulus. Therefore, over a prolonged period of
time, it is almost entirely the parathyroid system that sets the long term level of
calcium ions in the ECF. When the thyroid gland is removed, and calcitonin is no
longer secreted, the long term blood calcium ion concentration is not measurably
altered, which again demonstrates the overriding effect of the parathyroid hormonal
system of control.
DISORDERS OF CALCIUM METABOLISM :
Hypoparathyroidism : Can occur due to accidental damage or removal of the
parathyroids during surgery of the thyroid or in cancer of larynx.
- Spontaneous hypoparathyroidism can occur which may be hereditary.
- DiGeorge syndrome (very rare) in some cases of hereditary hypoparathyrodisim,
more than 1 endocrine gland Eg. parathyroid, ovary, adrenal cortex and thymus
may be involved.
Pseudohypoparathyyroidism :
- PTH level is high but serum calcium level is low.
- There is some fault in the PTH receptors of the target cell Thus producing signs
and symptoms characteristic of hypoparathyroidism.
TETANY :
- The outstanding sign of calcium deficiency is tetany.
- When serum calcium level falls, the irritability of nerves and NMJ rises and the
muscle contracts when subjected to subthreshold stimulus.
- Basic feature of tetany is uncontrolled, painful, prolonged contraction (spasm) of
the voluntary muscles.
- When the ECF concentration of calcium ions falls below normal, the nervous
system becomes excitable because this causes increased neuronal membrane
permeability to Na++ ions, allowing easy initiation of action potential.
- If calcium concentration in plasma is about 50% below normal, peripheral nerve
fibres become so excitable that they begin to discharge spontaneously, initiating
trains of nerve impulses that pass to the peripheral skeletal muscles to elicit tetanic
muscle contraction.
- Tetany occurs in hand before it develops in other parts of the body. This is called
carpopedal spasm or Accouchers hand.
a) Accouchers Hand :
- There is muscular spasm leading to uncontrolled prolonged flexion of the
metacarpophalangeal joints while the fingers remain extended.
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The term accoucher means obstetrician in charge of a labour room (sometimes


the obstetrician has to bring out intrauterine contents like retained placenta by
fingers. During such procedures, the accouchers hand assumes the above
described posture).
b) Laryngismus stridulous / laryngeal stridor :
- There is spasm of the larynx, the breathing stops and patient tries violently to
inspire.
- After sometime, the spasm disappears, the air enters the layrnx with a
characteristic crowing sound.
- This crowing sound during inspiration, after a phase of forcible stoppage is called
laryngeal stridor.
c) Chvosteks Sign : Tapping the facial nerve at the ramus of the mandible, in front
of the ear, produces painful spasm of the facial muscles.
d) Trousseaus sign : The sphygmomanometer cuff/BP cuff is applied to the upper
arm and inflated to above the systolic blood pressure for upto 3 minutes the
hand goes into spasm and develops the posture of accouchers hand.
Diagnosis : Serum calcium level usually < 7 mg%.
Treatment :
1. Temporary measures : Injections of soluble calcium salt. 10 ml of 10% calcium
gluconate should be given slow intravenous.
2. Long term measures Large dose of Vitamin D (100,000 units /day), along with
1-2 gms of calcium. At times it might be necessary to administer 1, 25 DHCC
instead of the non-activated form of Vitamin D because of its much more potent
and much more rapid action. This can also cause the unwanted effects because it
is sometimes difficult to prevent overactivity by the activated form of Vitamin D.
NOTE :
- PTH injections in tetany are not recommended because too expensive.
- Its effect lasts only for a few hours at the most.
- Such injections lead to antibody formation against PTH which nullifies the PTH
injected.
II. HYPERPARATHYROIDISM :
Due to increase activity of parathyroids :
Classification :
- Primary
- Secondary
- Tertiary
Primary Hyperparathyroidism :
- Increased PTH Increased serum calcium Causes :
1) Parathyroid adenoma
2) Hyperplasia
3) Carcinoma.
Clinical Features :
a) Osteitis Fibrosa Cystica or Von Recklinghausens Disease :
-

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Here intense osteoclastic resorption leads to destructive cystic changes involving


many bones. Bone pain is a prominent symptom, pathological fractures are
common, and sometimes tumour like masses of osteoclasts are formed.
- These brown tumours, closely resemble giant cell tumours of bone and are seen
typically at sites which normally contain hematopoietic tissue, skull, jaw, ribs and
spine.
- Called as browns tumour because of haemorrhage and hemosiderin pigmentation
within the tumour.
- The first indication of the condition is a cyst like lesion of the jaw. The
radiographic description is of a ground glass appearance of the affected bone.
There is resorption of bone, and although the lamina dura may be lost, the teeth
are not usually affected.
b) Generalized osteoporosis
c) Death is due to hypercalcemic crisis : There is shock, hemoconcentration, anuria,
and death preceded by confusion and coma.
d) Renal calculus formation / Nephrolithiasis : Due to increased serum calcium level
there is increased calcium absorption from the kidneys Patient prone to
develope renal stones can cause renal ischemia. Metastatic calcifications are
also seen in other soft tissues like blood vessels.
e) Abdominal groans : Calcium stimulates gastrin which is the powerful stimulator
of acid which may result in pain abdomen, due to peptic ulcer.
f) Psychic moans : Altered mental status ranging from weakness and lethargy to
confusion and dementia.
Secondary Hyperparathyroidism : Increased PTH, Decreased serum calcium causes
a) Renal diseases
b) Malabsorption
Hyperplasia of the parathyroids occurs in many types of osteomalacia and
rickets. In some cases, the PTH secretion is sufficiently marked to initiate
osteoclastic activity in the bones, and therefore in addition to the changes or rickets or
osteomalacia, there develop those of osteitis fibrosa cystica. Real disease is the usual
antecedant.
Renal rickets : Chronic renal disease, especially in young people is sometimes
attended by skeletal lesions and calcification defects Osteomalacia and osteitis
fibrosa cystica.
Tertiary hyperparathyroidism :
Increased PTH, Increased serum calcium.
Cause : Adenoma or enlargement of gland (Permanent damage).
Ectopic parathyroid Hormone syndrome;
A number of patients with malignant disease have hypercalcemia without
evidence of metastatic bone disease. This syndrome is due to the elaboration by the
tumour of a substance resembling parathyroid hormone. Squamous cell CA of the
lung and CA of the kidney are the usual culprits.
Diagnosis :
-

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Clinical examination of the neck may not reveal any parathyroid


enlargement.
- Diagnosis by various symptoms
- Serum calcium levels are always raised
- Serum PTH levels are raised detected by immunoassay tumour marker.
Treatment :
1) Surgical removal of some part of parathyroid gland.
2) Adenoma excision
3) Active Vitamin D metabolism
4) Renal transplantation
5) For renal stones Solubility of most renal stones is slight in alkaline media,
tendency for formation of renal calculi is greater in alkaline urine than in acid
urine. Therefore acidic diets and acidic drugs are used for treating renal calculi.
HYPOCALCEMIA :
The following are important causes of hypocalcemia :
1) Hypoparathyroidism
2) In association with hypoalbuminemia
3) Renal failure : Phosphate retention leads to hyperpohosphatemia and a reciprocal
lowering of the plasma calcium. Another important factor is the deficient
formation of 1, 25 HCC with a consequent impairment in the intestinal absorption
of calcium.
4) Vitamin D deficiency
5) Widespread osteoplastic metastasis These may utilize so much calcium that
hypocalcemia results. The usual primary source of the tumour is the prostate.
6) Infantile hypocalcemia : Neonatal tetany is well recognized and is due to
functional immaturity of the parathyroid glands during the first 2 days of life.
7) Acute pancreatitis : Hypocalcemia in this condition can be attributed partly to the
deposition of calcium salts in the foci of fat necrosis (dystrophic calcification),
and partly to the release of glucagon from the damaged pancreas.
Effects of Hypocalcemia :
1) Tetany : Trousseaus sign
Chvosteks sign
Laryngeal stridor
Mental disturbances
2) Abdominal pain of obscure origin. It may be due to smooth muscle spasm.
3) A predisposition to eczema in chronic cases. There is also an increased incidence
of candida albicans infections of the skin.
4) Cataract, a well known complication of chronic hypocalcemia. The cause is
uncertain.
5) Electrocardiographic changes : A prolonged QT interval principally in the ST
segment.
Treatment :
Same as that of hypoparathyroidism.
-

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HYPERCALCEMIA :
Causes for hypercalcemia :
1) Primary hyperparathyroidism
2) Hypervitaminosis D : excessive administration of vitamin D leads to
hypercalcemia and generalized metastatic calcification. The parathyroid
hormone like activity of vitamin D potentiates this action.
3) Vitamin D sensitive states : The hypercalcemia sometimes encountered in
sarcoidosis is probably due to increased sensitivity to Vitamin D.
4) Destructive bone lesions : Extensive destruction of the skeleton by osteolytic
metastases of carcinoma, multiple myeloma, or Hodgkins disease may lead to the
release of excessive amounts of calcium.
5) Miscellaneous causes :
a) Milk alkali syndrome : Where excess milk and antacids like NaHCO 3 are
given to treat peptic ulcers.
b) Excess thiazide therapy Like in cases of congestive cardiac failure, can
cause hypercalcemic state.
c) Prolonged immobilization
d) Hyperthyroidism
e) Congenital hypophosphatasia
Effects of Hypercalcemia :
1) Fatigue, lethargy and muscle asthenia
2) Anorexia, nausea and vomiting. Constipation is prominent, possibly due to the
muscular hypotonia.
3) Pruritus
4) Psychotic manifestations
5) Symptoms of progressive renal dysfunction starting with polyuria due to an
unresponsiveness of the distal and collecting tubules to antidiuretic hormone.
There is an accompanying thirst, which may also be due to the high plasma
calcium directly stimulating the hypothalamus. Ultimately leads to disturbances
in glomerular function Renal failure.
6) Metastatic calcification.
7) ECG changes : Shortened QT interval and depressed T waves.
8) Peptic ulceration : The excess plasma calcium releases gastrin.
9) Pancreatitis, both acute and chronic Common with primary
hyperparathyroidism. Etiology is unknown but suggested factors include stones
forming in the pancreatic ducts and ioinised calcium favouring the conversion of
trypsinogen to trypsin in the pancreatic ducts.
VITAMIN D DEFICIENCY :
Deficiency of vitamin D may result from :
i)
Reduced endogenous synthesis due to inadequate exposure to sunlight.
ii)
Dietary deficiency of Vitamin D
iii)
Malabsorption of lipids due to lack of bile salts such as biliary obstruction,
pancreatic insufficiency and malabsorption syndrome.

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iv)

Derangement of Vitamin D metabolism as occur in kidney disorders, liver


disorders etc.
v)
Resistance of end-organ to respond to Vitamin D.
Vitamin D Deficiency:
- Rickets in growing children
- Osteomalacia in adults
- Hypocalcemia tetany due to neuromuscular dysfunction
Rickets :
The primary defects in rickets are :
- Interference with mineralisation of bone.
- Deranged endochondral and intramembranous bone growth.
In the growing child, calcification of the epiphyseal cartilage does not occur at the
growing ends of the long bones. The cartilage therefore does not die and instead
continues to grow, so that the epiphyses undergo enlargement at the bone ends with
greatly delayed ossification.
Skeletal Changes :
i)
Craniotabes : In infants there is thickening of the frontal and parietal
eminentia, and flattening and thinning of the occipital region. The skull looks
square and box-like.
ii)
Harrisons sulcus : Appears due to indrawing of soft ribs on inspiration.
iii)
Rickety rosary : Deformity of chest due to cartilaginous overgrowth at
costochondral junction.
iv)
Pigeon-Chest Deformity : Is the anterior protrusion of sternum due to action of
respiratory muscles.
v)
Brew Legs : Occur in ambulatory children due to weak bones of lower legs.
vi)
Knock Knees : May occur due to enlarged ends of the femur, tibia and fibula.
vii)
Lower epiphyses of radius may be enlarged
Treatment :
- Supplying adequate calcium and phosphate in the diet.
- Administering large amounts of vitamin D. If vitamin D is not
administered, little calcium and phosphate are absorbed from the gut.
OSTEOMALACIA :
- Also called as adult rickets
- There is failure of mineralisation of the osteoid matrix
Cause of Osteomalacia :
- Dietary deficiency
- Poor endogenous synthesis of vitamin D.
It is more common in women, because pregnancy imposes an additional drain on the
supplies of calcium. In the normal adult, bone is continually being remodelled it is
removed by osteoclasts and replaced by osteoblasts laying down osteoid which
promptly calcifies. If this calcification fails, the bones consist largely of osteoid and
the result is osteomalacia i.e. there is an abundance of osteoid but poor calcification.
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(Note : Osteoporosis Where the matrix is normally calcified but reduced in


quantity).
Clinical Features :
- Muscular weakness
- Vague bony pains
- Fractures following trivial trauma
- Green stick fractures
RENAL RICKETS :
- Renal rickets is a type of osteomalacia that results from prolonged kidney damage.
The cause of this condition is mainly failure of the damaged kidneys to form 1, 25
DHCC, the active form of vitamin D. In patients whose kidneys have been
removed or destroyed and who are being treated by hemodialysis, the problem of
renal rickets is often a severe one.
Another type of renal disease that leads to rickets and oteomalacia is congenital
hypophosphatemia resulting from congenitally reduced reabsorption of phosphates by
the renal tubules. This type of rickets must be treated with phosphate compounds
instead of calcium and Vitamin D, and it is called Vitamin D resistant rickets.
TETANY IN RICKETS :In the early stages of rickets, tetany almost never occurs
because the parathyroid glands continually stimulate osteoclastic resorption of bone
and therefore maintain an almost normal level of calcium in the ECF.
However, when the bones finally become exhausted of calcium, the level of calcium
may fall rapidly. As the blood level of calcium falls below 7 mg/100 ml of blood, the
usual signs of tetany develops and the child may die of tetanic respiratory spasm
unless intravenous calcium is administered, which relieves the tetany immediately.
OSTEOPOROSIS :
Osteoporosis is the most common among all bone diseases in adults,
especially in old age. Here there is diminished organic bone matrix rather than poor
bone calcification. In osteoporosis, the osteoblastic activity in the bone usually is less
than normal and consequently the rate of bone osteoid deposition is depressed. This
reduction in bone mass results in fragile skeleton which is associated with increased
risk of fractures and consequent pain and deformity.The condition is particularly
common in elderly people and more frequent in post-menopausal women. The
condition may remain symptomatic or may cause only backache. However more
extensive involvement is associated with fractures.
Pathogenesis :
Osteoporosis is classified into 2 major groups.

Primary Idiopathic, involutional.

Secondary
Primary ostoeporosis : Results primarily from osteopenia without an underlying
disease or medication.
Increased osteoclastic resorption and slow bone formation.
Idiopathic type :
- In young and juveniles
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- Less common
Involutional type :
- Postmenopausal women and elderly people
- More common
Risk Factors :
1. Sex : More frequent in females than in males.
2. Decreased physical activity: As in old age.
3. Deficiency of sex hormones :
Oestrogen deficiency (Postmenopausal osteoporosis) in women
Androgen deficiency in men
4. Combined deficiency of calcitonin and estrogen
5. Hyperparathyroidism
6. Vitamin D deficiency
Secondary Osteoporosis : Due to number of factors and conditions.
- Immobilization
- Chronic anemia
- Acromegaly
- Hepatic disease
- Hyperparathyroidism
- Starvation
- Medications like administration of anticonvulsant drugs, heparin (large
dose).
Diagnosis :
- Radiographic evidence becomes apparent only after more than 30% of
bone mass has been lost.
- Levels of serum calcium, inorganic phosphorous and alkaline phosphatase
are usually within normal limits.
HETEROTOPIC CALCIFICATION :
- Is defined as the deposition of calcium salts in tissue other than osteoid or
enamel.
- Detected by radiographs because of its radiopacity.
Heterotopic Calcification can be of 2 types :
- Dystrophic calcification
- Metastatic calcification
DYSTROPHIC CALCIFICATION :
It is the deposition of calcium salts in dead or degenerated tissues. Eg. areas
of tuberculous necrosis, blood vessels in arteriosclerosis, scars and areas of fatty
degeneration.
Pathogenesis :
This type of calcification is not dependent upon an increase in the amount of
circulating blood calcium, but appears to be related to a change in the local condition
of the tissues. A local alkalinity in comparison with adjacent undamaged tissues

21

appears to be an important factor in initiating the precipitations of calcium in


degenerating or non-vital tissues.
Clinical Features :
It may be found, intraorally in gingiva, tongue or cheek, pulp of teeth.
Calcific degeneration of pulp can be classified into 2 types :
i)
Nodular type
- Found in coronal portion of the pulp chamber
- Calcification of hyalinized connective tissue
- Increase in size of calcium deposition along the collagenous fibrils.
ii)
Calcitonin around necrotic cells
- Radicular portion of pulp canal
- Nidus in the centre
- Increase in size by concrescence
Pulp Stones :
- True
- False
True denticles / pulp stones : Localized masses of calcified tissue that resemble dentin
because of their tubular structure.
True Pulp Stones :
- Free denticle
- Attached denticles.
Free Denticles : Denticles lying entirely within the pulp tissue and not attached to the
dentinal walls are called free denticles.
Attached Denticles : Denticles which are continuous with dentinal walls.
False Denticles : Localized masses of calcified material and unlike true denticles, do
not exhibit dentinal tubules.
METASTATIC CALCIFICATION :
- Calcium salts are precipitated in previously undamaged tissue.
- This precipitation is due to an excess of blood calcium.
Sites commonly seen :
Kidney
- Most frequent and important site
- Deposition occurs especially around the tubules, called nephrocalcinosis can
lead to renal failure.
- Lung, stomach, blood vessel wall, cornea, etc.
Causes of Metastatic Calcification :
- Hyperparathyroidism
- Excessive absorption of calcium from the bowel
- Hypervitaminosis D
- Destructive bone lesions Eg. metastatic carcinoma in bone and multiple
myeloma.

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CONCLUSION :
Calcium ions play an important role in many physiological functions bone
rigidity, permeability, muscle contraction, blood clotting, and prevention of many
disorders. But excess of calcium is harmful to the body. Thus calcium balance in the
body should be maintained.

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