Calcium metabolism1

CALCIUMCALCIUM
METABOLISMMETABOLISM
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 IntroductionIntroduction
 SourcesSources
 AbsorptionAbsorption
 DistributionDistribution
 ExcretionExcretion
 RegulationRegulation
 DisordersDisorders

 Minerals are required for natural growth and maintainance
of body
 Average adult human body contains 1to 2 kg of calcium of which 99%
is in skeleton along with phosphorus to form hydroxy apetite crystals
 ECF has more ca than ICF
 The calcium of extracellular fluid is critical for variety of functions and
remarkably constant
ECF 2.5mmol/l , ICF 10mmol/l
Normal adult range is 8.9 to 10.4 mmol/l

BODY DISTRIBUTION - The calcium in plasma is of 3 types-
1) IONIZED CALCIUM (diffusible)
2) PROTEIN BOUND CALCIUM
3) COMPLEXED CALCIUM TissueTissue CalciumCalcium
SkeletonSkeleton 9999
Soft tissuesSoft tissues 11
ExtracellularExtracellular
fluidfluid
<0.2<0.2
Total [g (mol)]Total [g (mol)] 1000(25)1000(25)
DIETARY SOURCES – It is widely distributed in food substances
HIGH SOURCE - Milk and cheese, cows milk 100mg/100ml
MEDIUM SOURCE - Fish and vegetables
SMALL AMOUNT - Nuts ,beans, cabbage,cereals
Distribution of Calcium

CALCIUM EQUILIBRIUM There is neither acculumation
nor loss of Ca in the body in take is equal to excretion.
Positive Calcium balance that is increased intake than
excretion
Negative Calcium balance in case of bone disease
Daily Requirements
ADULTS : 800mg
WOMENS in pregnancy and lactation : 1.2gm
INFANT under 1 yr : 360 - 540mgm
CHILDEREN 1 to 8 yr : 0.8 - 1.2gm

ABSORPTION - About 40%of average daily dietary intake of ca is
absorbed from gut . Ca is absorbed mainly from the
duodenum and first half of jejunum against electrical
and concentration gradient.
MECHANISM – Two mechanism
 Simple diffusion –occur in small intestine
 An active transport-Where ca is absorbed against con gradient and is
dependent on 1,25DHCC which regulates synthesis of ca binding
protein

FACTORS AFFECTING ABSORPTIONFACTORS AFFECTING ABSORPTION
 PH of intestinal milieu – Acidic PH favours ca absorptionPH of intestinal milieu – Acidic PH favours ca absorption
 COMPOSITION OF THE DIETCOMPOSITION OF THE DIET
 High protein diet – A high protein diet favours absorption. 15% ofHigh protein diet – A high protein diet favours absorption. 15% of
dietary ca is absorbed but if protein content is low only 5% is absored.dietary ca is absorbed but if protein content is low only 5% is absored.
Reason – Amino acids increases the solubility of ca salts and thus itsReason – Amino acids increases the solubility of ca salts and thus its
absorption. Lysine and arginine obtained from basic proteins causeabsorption. Lysine and arginine obtained from basic proteins cause
maximal absorption of ca .maximal absorption of ca .
 Fatty acids –In malabsorption syndrome, fatty acids are not absorbedFatty acids –In malabsorption syndrome, fatty acids are not absorbed
properly. Fatty acid produce insoluble ca soaps which are excreated inproperly. Fatty acid produce insoluble ca soaps which are excreated in
faeces, thus decreasing ca absorption.faeces, thus decreasing ca absorption.

 Sugar and organic acid- organic acids produced by microbial fermentationSugar and organic acid- organic acids produced by microbial fermentation
of sugar in gut, increases the solubility of ca salts and increases theirof sugar in gut, increases the solubility of ca salts and increases their
absorption. Citric acid also increases absorption of ca.absorption. Citric acid also increases absorption of ca.
 Phytic acid- cereals contain phytic acid which forms insoluble ca salts andPhytic acid- cereals contain phytic acid which forms insoluble ca salts and
decreases the absorption of ca.decreases the absorption of ca.
 Oxalates- Present in vegetables like cabbage and spinach forms insolubleOxalates- Present in vegetables like cabbage and spinach forms insoluble
ca oxalate which are excreted in faeces thus lowering ca absorption.ca oxalate which are excreted in faeces thus lowering ca absorption.
 Fibers- Presence of excess of fibers also interfere with absorption.Fibers- Presence of excess of fibers also interfere with absorption.

MINERALSMINERALS
 Phosphate and magnesium decreases absorption absorption of ca.Phosphate and magnesium decreases absorption absorption of ca.
 Ca : p ratio- A ratio of food Ca to P not more than 2:1 and not less than 1:2 isCa : p ratio- A ratio of food Ca to P not more than 2:1 and not less than 1:2 is
necessary for optimal absorption of ca.necessary for optimal absorption of ca.
 Fe in diet –Food Fe may form insoluble ferric phosphates. These indirectlyFe in diet –Food Fe may form insoluble ferric phosphates. These indirectly
increases the Ca: P ratio in the gut beyond range of optimal absorption.increases the Ca: P ratio in the gut beyond range of optimal absorption.
 Vitamin D – Promotes ca absorption.Vitamin D – Promotes ca absorption.

EXCRETION OF CALCIUM
About 2/3rd of the calcium in the glomerular filtrate is reabsorbed
in the proximal tubules. Then followed by ascending limbs of the
loops of henle and in the distal tubules and collecting ducts
reabsorption of the remaining is very great, so that almost no
calcium is lost in the urine on the other hand, even a minute
increase in calcium ion concerntration above normal increases
calcium excretion of markedly.

MULTIPLE BIOLOGICAL FUNCTIONS OF CALCIUM
 Calcium along with phophorus is essential for the form and
development of bones and teeth – a reserviour
Required for blood co-aggulation process
Regulate the excitability of nerve fibers
Essential for muscle contraction
Ca acts as 2nd
messenger in hormonal action
Regulates in release of hormones and neurotransmitters.
Maintain memberane integrity and plasma membrane
transport

FUNCTION OF CALCIUM
1. Activation of Enzymes
Ca + calmodulin Ca bound calmodulin kinase
phosphorylation
active kinase Enzyme active enzyme
Enzyme activated by Calcium are eg: Glycogen syn, pyruvatedehydrogen,
pyruvatekinase
Direct Ca action - coagulation, pancreatic lipase.

Excitation and Contraction of Muscles
Muscle contraction is modulated by Troponin and tropomyocin through
calcium which is a physiologic regulator of contraction.
In resting muscle Ca is in sarcoplasmic reticulum.
The nerve impulse releases Ca from SR stores Troponin C which has
high affinity and low affinity terminals.
In resting muscles only high affinity are occupied by Ca, when Ca is
released from SR low affinity sites are also occupied by Ca. calcium on
entering the cell binds with protein calmodulin. It has four sites which
binds with calcium. This leads to activation and inhibition of kinase
proteins.
Smooth muscle contraction: caused by activation of myosine.
Skeletal muscle contraction: activation of troponin c.

In smooth muscles, contraction is by Ca mediated phosporylation
of myocin light chain.
Secretion of Hormones such as insulin, PTH, Calcitonin and
vasopressin is mediated by Ca.
Ca and cAMP are second messengers for different hormones, eg:
glucagon.
Ca helps in coagulation process factor IV
In myocardium Ca prolongs systole.
In hypercalcemia cardiac arrest
Bulk of Ca is used in bone and teeth formation

Table 1: Regulation of Calcium and Skeletal Metabolism
Mineral - Calcium (Ca)
Organ Systems - Skeleton
Kidney
GI tract
Hormones - Parathyroid Hormone (PTH)
Calcitonin (CT)
Vitamin D [1,25(OH2)D]

ACTION AND CONTROL OF PARATHYROID HORMONE SECRETION
Parathyroid harmone provides a powerful mechanism for
controlling extracellular calcium and phosphate concentration by
regulating intestinal reabsorption, renal excretion and exchange
between the extracellular fluids and bone.
Anatomy of parathyroid gland
Normally there are four parathyroid glands in humans located
immediately behind the thyroid gland one behind each lobe.
Parathyroid gland is 6mm long, 3mm wide and 2mm thick.

The control of PTH secretion depends on the concentration of
free-ionized calcium circulating through the parathyroid glands. A
fall increases the rate of PTH secretion which, until the calcium
concentration returns to normal. PTH secretion is also affected
by the extracellular magnesium concentration and is decreased
by severe chronic hypomagnesaemia. It is not known to be
controlled by any other endocrine gland

MECHANISM OF ACTION
Agents which increase cAMP intracellularly enhance secretion of PTH.
These agents are PG and β-adrenergic agonist
 How cAMP causes secretion of PTH
Activation of Adrenylate cyclase increased intracellular
cAMP increased intracellular Ca phosphorylation of
specific intracellular protein by kinase activation of protein that finally
mediate the biologic action of the hormone.
 Effect of PTH on bone
It causes bone destruction because of release of Ca from the bone by
osteoclast causing bone resorption.
At low concentration of PTH bone remodeling with increase osteoblast
PTH acts on osteoblast to release IL 1 & 6 and leukemia inhibiting factor.
IL 1 & 6 stimulates monocytes to migrate into the bone.
LIF converts monocytes into osteoclast which causes bone resorption.

 Effect of PTH on intestinal mucosa
PTH converts vit D into 1,25 DHCC in the kidney and it
causes absorption of Ca by Gut.
 Effect of PTH on kidney
PTH increases renal tubular resorption of calcium and
diminishes phosphate resorption. Resorption of calcium occur
mainly in the late distal tubules, the collecting tubules and the
ascending loop of Henle.

Effect on bone
Rapid phase: occurs in minutes to hours.
activation of osteocytes already existing.
Second phase: from several days to weeks.
proliferation of osteoclasts causing increased bone
resorption.
Osteolysis: (rapid phase)
Bone resorption occurs in two sites 1) osteocytes present within bone cell
2) osteoblast along the bone surface
Osteocytes and osteoblasts form system of inter connected cell along bone
surface.
Osteocytic membrane system:
Long filmy process runs from osteocytes to osteoblasts.
Between osteocytic membrane system and bone there is “bone fluid”.
Osteocytes and osteoblasts has receptors for parathyroid harmone so there is
transfer of calcium from bone fluid to extracellular fluid.
Slow phase:
Receptors are present on osteocytes and osteoblasts. They act as secondary
messenger on osteoclasts and causes bone resorption.

EFFECTS OF PARATHYROID HORMONE ON CALCIUM AND
SKELETAL METABOLISM
Bone
Increases resorption
Increases formation, especially at low and intermittent
concentrations
Kidney
Decreases calcium excretion (clearance)
Increases phosphorus excretion
GI Tract
Increases calcium and phosphorus absorption
Indirect effect via 1,25?D production
Blood
Increases calcium
Decreases phosphorus

CALCITONIN
A peptide hormone, of which eight forms in five species
are known; composed of 32 amino acids and produced by the
parathyroid, thyroid, and thymus glands; its action is opposite
to that of parathyroid hormone in that calcitonin increases
deposition of calcium and phosphate in bone and lowers the
level of calcium in the blood. Synthesis and secretion of
calcitonin occurs in parafollicular cells lying in the interstitial
fluid between follicles of thyroid gland.

EFFECT OF CALCITONIN IN DECREASING PLASMA CALCIUM
CONCENTRATION
Calcitonin decreases blood Ca ion concentration very rapidly
beginning within minutes after injection of calcitonin. Thus the effect
of calcitonin on blood calcium ion concentration is exactly opposite
that of parathyroid hormone and it occurs several times as rapidly
calcitonin reduces plasma calcium concentration in at least two
separated ways.
The immediate effect - causes of osteoblastic activity
- inhibition of osteoclastic activity
It prevents formation of osteoclasts
Calcitonin also has minor effects on calcium handling in the kidney tubules and
intestinal tract again the effects are opposite those of parathyroid hormone

Calcitonin has weak effect on plasma calcium concentration
in adult humans.
Reasoning being initial reduction of calcium concentration caused
by calcitonin leads within hours to a powerful stimulation of
parathyroid secretion which over rides the calcitonin effect.
In adults the rate of absorption and depositon of calcium are small.
In case of children the effect is greater because of bone
remodelling.

EFFECTS OF CALCITONIN ON MINERAL METABOLISM
Bone
Inhibits resorption
Promotes formation
Kidney
Increases calcium excretion
Increases phosphorus excretion
GI Tract
Inhibitory effect on calcium/phosphorus absorption
Blood
Decreases calcium
Decreases phosphoruswww.indiandentalacademy.com

HORMONE REGULATING MINERAL METABOLISM
Vitamin D and its role in calcium and phosphate
absorption:
Vitamin D has a potent effect on increasing calcium
absorption from the intestinal tract, is also has important
effect on both bone deposition and bone reabsorption, vit.
D itself is not the active substance that actually causes
these effects, instead the vit D must first be converted
through a succession of reactions in the liver and the
kidney to final active product 1, 25-dihydroxychole-
calciferol. www.indiandentalacademy.com

THE VITAMIN D COMPOUNDS
Several different compounds derived from
sterols belong to the vitamin D family, and all of these
perform more or less the same functions, the most
important of these, called vitamin D3, is cholecalciferol
and this substance is formed in the skin as a result of
irradiation of 7-dehydrocholesterol by ultraviolet rays
from the sun.

Conversion of cholecalciferol to 25-hydroxycholecalciferol in the liver
and its feed back control:
 The first step in the activation of cholecalciferol is to convert it
to 25-hydroxycholecalcified, which occurs in liver.
Formation of 1, 25-dihydroxycholecalciferol in the kidneys and its
control by parathyroid hormone:
 The conversion in the proximal tubules of kidneys of 25-
hydroxycholecalciferol to 1, 25-hydroxycholecalciferol to in the
absence of this hormone either name or almost none of parathyroid
hormone exerts a potent effect in determining the functional effects of
vitamin D in the body, specifically its effects on calcium absorption in
the intestines and its effects on bone.

MECHANISM OF ACTION
The active 1,25 DHCC acts as a typical hormone
Via blood it reaches the intestine. Formation of calcium
binding protein occurs in the intestinal epithelial cells. This
protein functions to transport calcium into the cell cytoplasm
then finally removed and transfered to ECF. . The rate of
calcium absorption in directly proportional to the quantity of
calicium binding protein.

Effects of 1,25?D (1,25?dihydroxyvitamin D) on Mineral Metabolism
Bone
Promotes mineralization of osteoid
Increases resorption at high doses
Kidney
Decreases calcium excretion
Decreases phosphorus excretion
Gastrointestinal Tract
Increases calcium absorption
Increases phosphorus absorption
Blood
Increases calcium
Increases phosphorus
OTHER

DISORDERS OF CALCIUM METABOLISM
Hypocalcemia
A decrease in total plasma calcium concentration below
8.8 mg/dL (2.20 mmol/L) in the presence of normal
plasma protein concentration.

ClassificationClassification
 PTH absentPTH absent
 Hereditary hypoparathyroidismHereditary hypoparathyroidism
 Acquired hypoparathyroidismAcquired hypoparathyroidism
 PTH ineffectivePTH ineffective
 Chronic renal failureChronic renal failure
 Lack of Vit DLack of Vit D

ETIOLOGY AND PATHOGENESIS
Hypoparathyroidism - Results from a deficiency in or absence of
PTH. It is characterized by hypocalcemia and hyperphosphatemia
and is often associated with chronic tetany. Hypoparathyroidism
usually results from the accidental removal of or damage to
several parathyroid glands during thyroidectomy. Transient
hypoparathyroidism is common after subtotal thyroidectomy.
Permanent hypoparathyroidism occurs in fewer than 3% of
expertly performed thyroidectomies.

SYMPTOMS neuromuscular irritability when mild causes muscle
causes cramps and tetany and severe acute hypocalcemia results in
tetanic paralysis of respiratory muscles, laryngospasm, severe
convulsions and death.
Long standing hypercalcemia results in cutaneous changes,
cataracts and calcification of basal ganglion of brain.
CAUSES
Accidental removal of gland during surgery but occasionally from
autoimmune destruction of the gland.
Pseudohypoparathyroidism
Biological active PTH is produced in this inherited disorder but there
is end organ resistance to its effects.
Clinical features are developmental anomalies includes
short stature
Short metacarpal or metatarsal bones
Mental retardation www.indiandentalacademy.com

Idiopathic Hypoparathyroidism is an uncommon
condition in which the parathyroid glands are absent or
atrophied. It may occur sporadically or as an inherited
condition.
RENAL TUBULAR DISEASE - Including Fanconi's syndrome
due to nephrotoxins such as heavy metals and distal renal
tubular acidosis, can cause severe hypocalcemia due to
abnormal renal loss of Ca and decreasing renal conversion to
active vitamin D.

Vitamin D deficiency is an important cause of
hypocalcemia. Vitamin D deficiency may result from
inadequate dietary intake or decreased absorption due to
hepatobiliary disease or intestinal malabsorption. It can
also occur because of alterations in vitamin D
metabolism as occurs with certain drugs (phenytoin,
phenobarbital, and rifampin) or lack of skin exposure to
sunlight. The latter is an important cause of acquired
vitamin D deficiency in northern climates among people
wearing dress that covers them completely (eg, Muslim
women in England.

MAGNESIUM DEPLETION - Occurring with intestinal
malabsorption or dietary deficiency can cause hypocalcemia. Relative
PTH deficiency and end-organ resistance to its action occur with
magnesium depletion, resulting in plasma concentrations of < 1.0
mEq/L (< 0.5 mmol/L); repletion of magnesium improves PTH levels
and renal Ca conservation
ACUTE PANCREATITIS - Causes hypocalcemia when Ca is
chelated by lipolytic products released from the inflamed pancreas

HYPOPROTEINEMIA - Of any cause can reduce the
protein-bound fraction of plasma Ca. Hypocalcemia due
to diminished protein binding is asymptomatic. Since the
ionized Ca fraction is unaltered, this entity has been
termed factitious hypocalcemia.
ENHANCED BONE FORMATION - With inadequate
Ca intake can cause hypocalcemia. This situation occurs
particularly after surgical correction of
hyperparathyroidism in patients with severe osteitis
fibrosa cystica and has been termed the hungry bone
syndrome

SEPTIC SHOCK - May be associated with hypocalcemia due
to suppression of PTH release and conversion of 25(OH)D3 to
1,25(OH)2D3.
HYPERPHOSPHATEMIA - Also causes hypocalcemia by one
or a variety of poorly understood mechanisms. Patients with renal
failure and subsequent phosphate retention are particularly prone to
this form of hypocalcemia

DRUGS - Associated with hypocalcemia include
those generally used to treat hypercalcemia
anticonvulsants (phenytoin, phenobarbital) and rifampin,
which alter vitamin D metabolism.

SIGNS AND SYMPTOMS
Symptoms primarily result from neuromuscular irritability.
Muscle cramps involving the back and legs are common complaints in
patients with hypocalcemia. Tetany characteristically results from
severe hypocalcemia. It can also result from reduction in the ionized
fraction of plasma Ca without marked hypocalcemia, as occurs in
severe alkalosis.
Tetany is characterized by sensory symptoms consisting of
paresthesias of the lips, tongue, fingers and feet; carpopedal spasm,
which may be prolonged and painful; generalized muscle aching; and
spasm of facial musculature. Tetany may be overt with spontaneous
symptoms or latent and requiring provocative tests to elicit. Latent
tetany generally occurs at less severely decreased plasma Ca
concentrations: 7 to 8 mg/dL (1.75 to 2.20 mmol/L).www.indiandentalacademy.com

CHVOSTEK'S and TROUSSEAU'S signs are easily
performed at the bedside to elicit latent tetany. Chvostek's sign is
an involuntary twitching of the facial muscles elicited by a light
tapping of the facial nerve just anterior to the exterior auditory
meatus. It is present in up to 10% of healthy people and is often
absent in chronic hypocalcemia. Trousseau's sign is the
precipitation of carpopedal spasm by reduction of the blood
supply to the hand with a tourniquet or BP cuff inflated to 20 mm
Hg above systolic BP applied to the forearm for 3 min

Treatment of hypocalceamiaTreatment of hypocalceamia
 Emergency treatment: calcium gluconate inj 0.23 mmolEmergency treatment: calcium gluconate inj 0.23 mmol
Ca/mlCa/ml
 Dose : 10ml iv in first instanceDose : 10ml iv in first instance
 Long term treatment: vitamin D therapyLong term treatment: vitamin D therapy
 Oral calcium tabletsOral calcium tablets
 Calcium gluconate 54mg Ca/tabCalcium gluconate 54mg Ca/tab
 Calcium gluconate 90mg/tabCalcium gluconate 90mg/tab
 Sandoz calcium 400mg /tabSandoz calcium 400mg /tab
 Sandoz calcium 135mg /tabSandoz calcium 135mg /tab

HYPERCALCEMIA
An increase in total serum calcium concentration above 10.4 mg/dL
bet 11.5 -12mg/dl.
Hypercalcemia can be manifestation of serious illness – malignancy can
be detected coincidentally by lab testing.
Whenever hypercalcemia is confirmed definite treatment must be given.
Hypercalcemia can also be the earliest clue to presence of malignancy.
Classification of Causes of Hypercalcemia
A) PTH related
i) Primarily hyperparathyroidism
a) Solitary adenoma
b) Multiple endocrine neoplasia
ii) Lithium therapy
iii) Familial hypocalcuric hypercalcemia

B) Vit D related
i) Vit D intoxication
ii) Increased 1,25 DHCC, sarcoidosis.
iii) Idiopathic hypercalcemia of infancy
C) Malignancy related
i) Solid tumor with metastasis
ii) Solid tumor with humoral mediation of hypercalcemia
D) Associated with High bone turn over
i) Hyperthyroidism
ii) Immobilization
iii) Thiazide
E) Association with renal failure
i) Severe secondary hyperparathyroidism
ii) Milk alkali syndrome www.indiandentalacademy.com

CLINICAL SYMPTOMS
Fatigue
Depreession
Muscle weakness
Weight loss
Mental confusion
Alteration in ECG ( Short Q T interval)
Nausea, vomiting, constipation
If value more than 13mg/dl there will be renal insufficiency
Calcification of kidney, skin, vessels and heart
If value more 15mg/dl there will be coma and cardiac arrest

Primary Hyperparathyroidism
1) Single adenoma
2) Adenomas are located at inferior portion of parathyroid gland
3) Chief cells are increased in adenoma
multiple endocrine neoplasia
MEN I (Wermer's syndrome) consists of hyperparathyroidism and
tumors of pituitary and pancreatic islet cells, often associated
with peptic ulcer and gastric hypersecretion (Zollinger – Ellison
syndrome
MEN II carcinoma of the thyroid
Secondary hyperparathyroidism
1) Chronic renal failure
2) Malabsorption
3) Osteomalacia & rickets

The unique bone involvement in hyperparathyroidism is osteitis
fibrosa cystica. In the past osteitis fibrosa cystica occurred in 10 to
25 percent of patients with hyperparathyroidism. Histologically the
pathognomonic features are a reduction in the number of trabeculae
and increase in the giant multinucleated osteoclasts in scalloped
areas on the surface of the bone. (Howship’s lacunae) and a
replacement of the normal cellular and marrow elements by fibrous
tissues. Loss of lamina dura of the teeth is less specific. Tiny
“punched out” lesions may be present in the skull, producing the so
called salt and pepper appearance.
Malignancy related hypercalcemia is thought to be due to local
invasion and destruction of bone by tumour cells.
Most solid tumor associated with hypercalcemia particularly squamous
cell carcinoma and renal tumors secrete cellular factors that are
believed caused increased bone resorption.
Classification
1) Hemolytic malignancies
a) Local bone destruction (IL1, TNF)

Local Bone Destruction
Multiple Myeloma
Lymphomas
2) Solid tumor
Local Bone destruction (PG)
IMMOBILIZATION - Particularly complete,
prolonged bed rest, can result in hypercalcemia due
to accelerated bone resorption. Hypercalcemia
develops within days to weeks of the onset of bed
rest in patients undergoing orthopedic casting
and/or traction, and in those with spinal injuries or
neurologic disorders.

Idiopathic HYPERCALCEMIA OF INFANCY- Is due to a group of
rare genetic disorders, all of which are associated with increased
intestinal absorption of Ca and may result from vitamin D toxicity or
increased sensitivity to vitamin D
Sarcoidosis normal relation between 25 DHCC are not
maintained. Normally if there is increase in 25 HCC there is no increase
in 1,25 DHCC but in sarcoidosis the site of synthesis of 1,25 DHCC is
macrophages or other cells associated granulomatous deposits.

Hyperthyroidism Mild elevation is common
Hypercalcemia will be due to bone turn over with bone resorption by
direct effect on skeleton.
Thiazide
Can cause hypercalcemia in patients with hyperthyroidism there is
high rate of bone turn over such as patients with high dose of vit D
Hyperparathyroidism associated with kidney failure
In progressive kidney disease
The initial tendency to hypercalcemia attributable to two causes 1)
phosphate retention that develops because of reduced excretion of
phosphate and reduced concentration of 1,25 DHH associated with
progressive renal damage. Chronic renal failure causes PTH
hyperplasia

Vit D intoxication ingestion of large doses of Vit D 50-100 times
more is required to produce hypercalcemia increased Vit D
causes increased intestinal Ca absorption.
In the milk-alkali syndrome, excessive amounts of Ca and
absorbable alkali are ingested, usually during peptic ulcer
therapy, resulting in hypercalcemia, renal insufficiency, and
metabolic alkalosis. The availability of H2-blocker therapy for
peptic ulcer disease has greatly reduced the incidence of this
syndrome

Lithium therapyLithium therapy
Used in psychiatric disorders causes hypercalcemiaUsed in psychiatric disorders causes hypercalcemia
Reversal of hypercalcemia occurs on withdrawalReversal of hypercalcemia occurs on withdrawal
Familial hypercalcuric hypercalcemiaFamilial hypercalcuric hypercalcemia
Autosomal dominant traitAutosomal dominant trait
Asymptomatic hypercalcemiaAsymptomatic hypercalcemia

Treatment of hypercalceamiaTreatment of hypercalceamia
Emergency treatment: the solution of IV infusion contains aEmergency treatment: the solution of IV infusion contains a
mixture of mono and dihydrogen phosphate so that ph ismixture of mono and dihydrogen phosphate so that ph is
7.4.7.4.
500ml of this solution should be infused over 4 to 6 hours.500ml of this solution should be infused over 4 to 6 hours.
Long term phosphate treatment:Long term phosphate treatment:
Oral phosphate is given as diphosphate. Choice depends uponOral phosphate is given as diphosphate. Choice depends upon
serum phosphate levels.serum phosphate levels.
Dose 100 to 300ml per day in divided dosesDose 100 to 300ml per day in divided doses
Phosphate sandoz tabletPhosphate sandoz tablet
Phosphorous :500mgPhosphorous :500mg
Na: 21 mmolNa: 21 mmol
K : 3mmolK : 3mmol
Dose: 1 to 6 tab dailyDose: 1 to 6 tab daily

Sulkowitch testSulkowitch test
 Test for serum calciumTest for serum calcium
 Sulkowitch test: Equal quantity of reagent is added toSulkowitch test: Equal quantity of reagent is added to
urineurine
 Test: urine 5 ml + 5 drops of 1% acetic acid + 5 mlTest: urine 5 ml + 5 drops of 1% acetic acid + 5 ml
potassium oxalatepotassium oxalate
 If no ppt Hypocalcium: 7.5 ml/dlIf no ppt Hypocalcium: 7.5 ml/dl
 Fine cloudy ppt: 9 -11mg/dlFine cloudy ppt: 9 -11mg/dl
 Heavy white ppt: HypercalcemiaHeavy white ppt: Hypercalcemia
 Interference: calcium is precipitated as calcium oxalate.Interference: calcium is precipitated as calcium oxalate.

OsteoporosisOsteoporosis
 Reduction in the mass of bone per unit volumeReduction in the mass of bone per unit volume
 Histologically, the disorder is characterized by aHistologically, the disorder is characterized by a
decrease in cortical thickness and in the numberdecrease in cortical thickness and in the number
and size of trabaculae of cancellous boneand size of trabaculae of cancellous bone
 Abnormal osteoblasts and osteoclasts relation isAbnormal osteoblasts and osteoclasts relation is
seenseen
 Bone resorption exceeds bone formationBone resorption exceeds bone formation

Classification of osteoporosisClassification of osteoporosis
 Common form of osteoporosis unassociatedCommon form of osteoporosis unassociated
with other diseasewith other disease
 Idiopathic osteoporosisIdiopathic osteoporosis
 Type 1 osteoporosisType 1 osteoporosis
 Type 2 osteoporosisType 2 osteoporosis
 Idiopathic osteoporosis – occurs in children and adults of bothIdiopathic osteoporosis – occurs in children and adults of both
sexes and is of unknown pathogenesissexes and is of unknown pathogenesis
 Type 1 osteoporosis – occurs in post menopausal womenType 1 osteoporosis – occurs in post menopausal women
 Type 2 osteoporosis – occurs in both male and females above 70Type 2 osteoporosis – occurs in both male and females above 70
yrs of ageyrs of age

Clinical featuresClinical features
 Pain in backPain in back
 Deformity of spineDeformity of spine
 Pain with slight movementPain with slight movement
 Pain is deep dull typePain is deep dull type

Radiologic featuresRadiologic features
 Decreased mineral densityDecreased mineral density
 Prominence of vertical striations due to greaterProminence of vertical striations due to greater
loss of horizontal trabaculaeloss of horizontal trabaculae
 Expansion of intervertebral discs resulting in soExpansion of intervertebral discs resulting in so
calledcalled codfishcodfish vertebravertebra

Rickets and osteomalaciaRickets and osteomalacia
 RICKETSRICKETS
 A growing skeleton is involvedA growing skeleton is involved
 Defective mineralization occur not only in boneDefective mineralization occur not only in bone
but also in cartilaginous matrix of growth platesbut also in cartilaginous matrix of growth plates
 OSTEOMALACIAOSTEOMALACIA
 Disorder in adults in whom epiphyseal growthDisorder in adults in whom epiphyseal growth
plates are closedplates are closed

CausesCauses
 Deficiency of Vit DDeficiency of Vit D
 Less exposure to sunlightLess exposure to sunlight
 MalabsorptionMalabsorption

Clinical findingsClinical findings
 Skeletal deformitySkeletal deformity
 Weak bonesWeak bones
 FractureFracture
 In case of children there is parietal flattening frontal bossingIn case of children there is parietal flattening frontal bossing
and widening of suturesand widening of sutures

Radiographic findingsRadiographic findings
 Cortex thinningCortex thinning
 Abnormality in trabaculaeAbnormality in trabaculae
 Ground glass appearanceGround glass appearance
 Specific feature is the presence of radiolucent bandsSpecific feature is the presence of radiolucent bands
ranging from few mm to several cms in lengthranging from few mm to several cms in length
usually perpendicular to the surface of the boneusually perpendicular to the surface of the bone
“looser’s zones”“looser’s zones”

HYPERPARATHYROIDISM
What is hyperparathyroidism?
Hyperparathyroidism is caused by overactive parathyroid glands.
Overactive parathyroid glands produce high levels of parathyroid hormones,
which, in turn, results in increased levels of calcium in the blood stream. The
excess calcium released by the bones leads to osteoporosis and
osteomalacia (both bone-weakening diseases). Another result of
hyperparathyroidism is kidney stones, because of high levels of calcium
excreted into the urine by the kidneys. Hyperparathyroidism is quite rare in
children.
What causes hyperparathyroidism?
Causes of hyperparathyroidism include benign (non-cancerous)
tumors on the parathyroid glands or enlargement of the parathyroid glands.

Causes of hyperparathyroidism include benign (non-cancerous)
tumors on the parathyroid glands or enlargement of the parathyroid
glands.
What are symptoms of hyperparathyroidism?
According to a recent study, children with hyperparathyroidism
experience more severe symptoms than adults. The following are the most
common symptoms of hyperparathyroidism in children. However, each
child may experience symptoms differently.

Symptoms may include:
kidney pain (due to the presence of kidney stones)
diminished bone density that causes bone pain
aches and pains
abdominal pain
nausea
vomiting
fatigue
excessive urination
confusion
muscle weakness

How is hyperparathyroidism diagnosed?
In addition to a complete medical history and physical
examination, diagnostic procedures for hyperparathyroidism
may include:
BONE X-RAY - a diagnostic test that uses invisible
electromagnetic energy beams to produce images of internal
tissues, bones, and organs onto film.

HYPOPARATHYROIDISM
What is hypoparathyroidism?
Hypoparathyroidism is caused by underactive parathyroid glands.
Underactive parathyroid glands produce too little parathyroid hormones,
which, in turn, causes low levels of calcium in the blood stream. The low levels
of calcium lead to tetany, an increased excitability of the nerves.
What causes hypoparathyroidism?
Causes of hypoparathyroidism include accidental removal of a
parathyroid gland when the thyroid is removed, or when part of the parathyroid
tissue is removed during surgery. Other causes include absent parathyroid
glands from birth or the sudden stop of functioning due to unknown reasons
(idiopathic). It is often associated with cardiac defects, such as DiGeorge.

What are the symptoms of hypoparathyroidism?
The following are the most common symptoms of
hypoparathyroidism. However, each child may experience
symptoms differently.
Symptoms may include:
uncontrollable, painful spasms of the face, hands, arms, and feet
seizures
T he symptoms of hypoparathyroidism may resemble other
problems or medical conditions. Always consult your child's
physician for a diagnosis.
How is hypoparathyroidism diagnosed?
In addition to a complete medical history and physical
examination, diagnostic procedures for hypoparathyroidism may
include blood tests to measure the parathyroid hormone levels.www.indiandentalacademy.com

METABOLIC BONE DISEASES
As mentioned earlier, calcium deficiency is just one type of
metabolic bone disease. What follows is a brief description of the most
commonly seen metabolic bone diseases.
OSTEOPOROSIS
Osteoporosis is a disease well known in humans as well as in
certain captive animals. This is a thinning of the bone matrix as more
calcium is resorbed into the blood than is deposited into the bone.
Rather than being caused strictly by a deficiency in calcium or excess
of phosphorus, true osteoporosis may be related to protein deficiency
(both dietary and due to prolonged anorexia),or through disuse of
bones. This may be as a result of being confined in too-small spaces, or
enforced inactivity such as that experienced when fractures have been
immobilized, or as a result of long-term paralysis.
Bones become brittle, light, and easily broken.

OSTEOMALACIA
This is softening of the bone and decreased bone density due to
decreased mineralization. The body tries to compensate by
depositing bone material at the sites of greatest tension. Folding
fractures and bowed bones are common.
RICKETS
Rickets is similar to osteomalacia, and occurs in the young. The
differences are most noticeable in x-rays as it affects the bones in
different ways. Bowing of the long bones, sometimes severely
deformed long bones, is the most common outward signs of
rickets.

Hyperparathyroidism
Hyperparathyroidism is caused by overactive parathyroid
glands. Overactive parathyroid glands produce high levels
of parathyroid hormones, which, in turn, results in
increased levels of calcium in the blood stream. The excess
calcium released by the bones leads to osteoporosis and
osteomalacia (both bone-weakening diseases). Another
result of hyperparathyroidism is kidney stones, because of
high levels of calcium excreted into the urine by the
kidneys. Hyperparathyroidism is quite rare in children

Diabetes & Other Endocrine and Metabolic Disorders
Hyperparathyroidism
Hyperparathyroidism is caused by overactive parathyroid glands. Overactive
parathyroid glands produce high levels of parathyroid hormones, which, in turn,
results in increased levels of calcium in the blood stream. The excess calcium
released by the bones leads to osteoporosis and osteomalacia (both bone-
weakening diseases). Another result of hyperparathyroidism is kidney stones,
because of high levels of calcium excreted into the urine by the kidneys.
Hyperparathyroidism is quite rare in children.
Causes of hyperparathyroidism include benign (non-cancerous) tumors on the
parathyroid glands or enlargement of the parathyroid glands.
What are symptoms of hyperparathyroidism?
According to a recent study, children with hyperparathyroidism experience more
severe symptoms than adults. The following are the most common symptoms
of hyperparathyroidism in children. However, each child may experience
symptoms differently

Both calcium and phosphorous, as well as magnesium, are transported
to blood from bone, renal, and GI cells, and vice versa (4-6). These
transport mechanisms can be through cells (transcellular) and around
cells (paracellular). The cellular transport is mediated by the membrane
structures illustrated in Figure 2 and by binding transport proteins (7,8).
The paracellular transport is generally passive and mediated by mineral
gradients. These mechanisms also involve corresponding co-
transportation and exchange-transportation with other ions, notably
sodium, potassium, chloride, hydrogen, and bicarbonate, some of which
are powered by ATP hydrolysis. Similar mechanisms allow for the
intracellular distribution of calcium, where it partitions primarily between
the mitochondria and cytosol. The details of the regulation

Hypocalcemia in newborns is discussed under
Metabolic Problems in the Newborn in Ch.
260.
Etiology and Pathogenesis
Hypocalcemia has a number of causes.
Several are listed below:
Hypoparathyroidism results from a deficiency
in or absence of PTH. It is characterized by
hypocalcemia and hyperphosphatemia and
is often associated with chronic tetany.
Hypoparathyroidism usually results from the
accidental removal of or damage to several
parathyroid glands during thyroidectomy.
Transient hypoparathyroidism is common
after subtotal thyroidectomy. Permanent
hypoparathyroidism occurs in fewer than 3%
of expertly performed thyroidectomies.

Manifestations of hypocalcemia usually begin about
24 to 48 h postoperatively but may first occur after
months or years. PTH deficiency is more common
after radical thyroidectomy for cancer or as the result
of an operation on the parathyroid itself (subtotal or
total parathyroidectomy). Risk factors for severe
hypocalcemia after subtotal parathyroidectomy
include severe preoperative hypercalcemia, removal
of a large adenoma at surgery, and elevated alkaline
phosphatase.

Drugs associated with hypocalcemia include those
generally used to treat hypercalcemia (see Hypercalcemia,
below); anticonvulsants (phenytoin, phenobarbital) and
rifampin, which alter vitamin D metabolism; transfusion
with blood products treated with citrate as well as
radiocontrast agents containing the divalent ion chelating
agent ethylenediaminetetraacetate.
Although excessive secretion of calcitonin might be
expected to cause hypocalcemia, low plasma Ca levels
rarely occur in patients with large amounts of circulating
calcitonin from medullary carcinoma of the thyroid

The clinical manifestations of hypocalcemia are due to
disturbance in cellular membrane potential. Symptoms primarily
result from neuromuscular irritability. Muscle cramps involving
the back and legs are common complaints in patients with
hypocalcemia. Slowly developing, insidious hypocalcemia may
produce mild, diffuse encephalopathy and should be suspected
in any patient with unexplained dementia, depression, or
psychosis. Papilledema occasionally may occur and cataracts
may develop after prolonged hypocalcemia. Severe
hypocalcemia with plasma Ca < 7 mg/dL (< 1.75 mmol/L) may
cause tetany, laryngospasm, or generalized convulsions

Tetany characteristically results from severe
hypocalcemia. It can also result from reduction in the
ionized fraction of plasma Ca without marked
hypocalcemia, as occurs in severe alkalosis. Tetany is
characterized by sensory symptoms consisting of
paresthesias of the lips, tongue, fingers and feet;
carpopedal spasm, which may be prolonged and painful;
generalized muscle aching; and spasm of facial
musculature. Tetany may be overt with spontaneous
symptoms or latent and requiring provocative tests to elicit.
Latent tetany generally occurs at less severely decreased
plasma Ca concentrations: 7 to 8 mg/dL (1.75 to 2.20
mmol/L).

Chvostek's and Trousseau's signs are easily performed at the
bedside to elicit latent tetany. Chvostek's sign is an involuntary
twitching of the facial muscles elicited by a light tapping of the
facial nerve just anterior to the exterior auditory meatus. It is
present in up to 10% of healthy people and is often absent in
chronic hypocalcemia. Trousseau's sign is the precipitation of
carpopedal spasm by reduction of the blood supply to the hand
with a tourniquet or BP cuff inflated to 20 mm Hg above systolic
BP applied to the forearm for 3 min

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