This seminar includes sources,daily requirement,metabolism i.e absorption and excretion of calcium and phosphate and various factors associated due to increase or decrease in the levels of calcium and phosphate within the body
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CALCIUM AND PHOSPHATE
METABOLISM
Karishma.S
II MDS
CONTENTS
•INTRODUCTION
•IMPORTANT MINERALS
•CALCIUM & PHOSPHOROUS METABOLISM
•HORMONES INVOLVED IN CALCIUM AND PHOSPHATE HOMEOSTASIS
•APPLIED ASPECTS
•SUMMARY
•CONCLUSION
•REFERENCES
IMPORTANT MINERALS
Macro Elements
Calcium
Magnesium
Phosphorus
Sodium
Potassium
Chloride
Sulfur
Trace Elements
Iron
Iodine
Copper
Manganese
Zinc
Molybdenum
Selenium
Fluoride
Calcium and phosphorous
individually have their own
functions and together they are
required for the formation of
hydroxyapatite and physical
strength of the skeletal tissue.
Most abundant mineral in many animals and in the
human body.
Ancient Romans prepared lime- calcium oxide. 975 AD
-plaster of Paris (calcium sulfate)was used for setting
broken bones.
Sir Humphry Davy Isolated calcium(1808)
Calcium
It is the second most abundant essential mineral in the human
body after calcium.
In human body Phosphorus is present as phosphates (compounds
containing the phosphate ion, PO
4
−3
)
The first form of elemental phosphorus to be produced was white
phosphorus, in 1669 by Greek .
Hennig Brand(1669) discovered.
PHOSPHORUS
ROLE OF CALCIUM IN BODY
Affects nerve and muscle physiology
Intracellular signal transduction pathways.
Co-factor in blood clotting cascade.
Constituent of bone and teeth.
Major structural element in the vertebrate skeleton (bones and teeth) in the
form of calcium phosphate (Ca
10
(PO
4
)
6
(OH)
2
known as hydroxyapatatite
Maintain all cells and connective tissues in the body.
Essential component in production of enzymes and hormones that regulate
metabolism
ROLE OF PHOSPHATE
Key constituent of bone and teeth.
Component of intra cellular buffering. Forms energy rich bonds in ATP.
Forms co-enzymes.
Regulates blood and urinary pH.
Forms organic molecules like DNA & RNA
Cellular energy metabolism.
Constituent of macro molecules like nucleic acids, phospholipids and
phosphoproteins.
DISTRIBUTION
1000-1500gm
(1.5% of the body weight)
99%
Bones
1%
ECF
Plasma
500-800gm
80-90%
Bones
Teeth
10%
RBC
Plasma
Total calcium Total phosphorus
PLASMA CALCIUM AND PHOSPHATE
Normal plasma levels
9-11mg/dl(calcium)
Normal plasma levels
2.5-4.5mg/dl(phosphorous)
Ionized Unionized
( 5 mg/dl) (4mg/dl)
organic Inorganic
(0.5-1mg/dl)
(Adults:3-4mg/dl)
(children:5-6mg/dl)
CALCIUM PHOSPHATE RATIO
Calcium : Phosphate ratio normally is 2:1
Increase in plasma calcium levels causes corresponding decrease in
absorption of phosphate.
This ratio is always constant.
Best source
Hard cheese
Milk
Dark green leafy vegetables
Good source
Ice-cream
Broccoli
Baked beans
Dried legumes
Dried figs
Fair source
String beans
Eggs
Bread
RDA OF CALCIUM
Average adult-800 mg/ day
Infants: <1yr- 360-540mg
1-10yr- 800mg
11-18yr- 1200mg
During pregnancy & lactation-1200mg/ day
SOURCES OF CALCIUM
Rich source
Milk
Meat
Fish
Poultry
Eggs
Moderate sources
Cereals
Pulses
Nuts
Legumes
Meat
RDA OF PHOSPHATES
Adults-800-1200mg/day
Infants-240mg/day
During pregnancy & lactation-1200mg/ day
SOURCES OF PHOSPHATE
ABSORPTION AND EXCRETION
OF CALCIUM AND PHOSPHATE
35-40% of average daily dietary Ca is absorbed from gut, mainly
duodenum and first half of jejunum by a carrier mediated active
transport under the influence of vitamin D
Additionla 25% of Ca enters the intestine via secreted gastrointestinal
juices and sloughed mucosal cells
Thus about 90% of daily intake of calcium is excreted in feces
PHOSPHORUS ABSORPTION
50-70%- absorbed
Small intestine- soluble inorganic phosphate
Except the portion of phosphate that is excreted in
combination with non absorbed calcium
Almost all dietary phosphate is absorbed from the
gut and later excreted in urine
RENAL EXCRETION OF CALCIUM AND
PHOSPHATE
10% - urine
41% - bound to protein and cannot
be filtered
Rest is filtered through glomeruli
PHOSPHOROUS EXCRETION
Is excreted primarily through Urine.
Almost 2/3
rd
of the total
phosphorous that is excreted is
found in the urine as phosphate of
various cations.
Phosphorous found in the faeces is
the non absorbed form of
phosphorous.
When calcium concentration
is low the reabsorption from
the renal tubules is greater
Even minute increase in
calcium increases excretion
markedly
Renal phosphate excretion runs
through overflow mechanism
Plasma level <1mmol/litre,all the
phosphate in glomerular filtrate is
reabsorbed
Above critical condition phosphate
loss is directly proportional to
additional increase
FACTORS CONTROLLING ABSORPTION
Factors inhibiting:
Phylates and oxalates
High dietary phosphate
Free fatty acids
High pH
High fiber diet
Factors promoting:
Vitamin D
Para thyroid harmone
Low pH
Lactose
Amino acids like lysine and
arginine
pH of intestine:
•Acidic pH in the upper intestine (deodenum)
increases calcium absorption by keeping calcium
salts in a soluble state.
• In lower intestine since pH is more alkaline,
calcium salts undergoes precipitation
Phytic acid and phytates:
•present in oatmeal, meat and cereals and are considered anti-
calcifying factors as they combine with calcium in the diet thus
forming insoluble salts of calcium
Oxalates:
•present in spinach and rhubarb leaves. They form oxalate precipitates
with calcium present in the diet thus decreasing their availability.
Fats:
•combines with calcium and form insoluble calcium , thus
decreasing calcium absorption.
Bile salts:
•increases calcium absorption by promoting metabolism of lipids.
Protein and aminoacids:
•increases calcium absorption as protein forms soluble complexes
with calcium and keeps calcium in a form that is easily
absorbable.
Carbohydrates:
•lactose promotes calcium absorption by creating the acidity in
the gut as they favours the growth of acid producing bacteria.
Rottenson -1938-amount of calcium stored in body is directly
proportional to amount of calcium absorbed in body
Increased level of calcium and phosphate in diet increases their
absorption however up to a certain limit.
This is because the active process of their absorption can bear with
certain amounts of load beyond which the excess would pass out into
faeces
AMOUNT OF DIETARY CALCIUM AND
PHOSPHATES :
Precipitation of calcium in non
osseous tissue under abnormal
conditions
Hydroxyapatite does not
precipitate in extracellular
fluid despite super saturation
of calcium and phosphorous
Pregnancy and growth:
HORMONAL CONTROL OF CALCIUM & PHOSPHATE
METABOLISM
Three hormones regulate calcium and phosphate
metabolism.
Vitamin D
PTH
Calcitonin
VITAMIN D
Cholecalciferol / D
3
Ergocalciferol / D
2
Can be called as hormone as it is produced in the skin when exposed
to sunlight.
Vitamin D has very little intrinsic biological activity.
Vitamin D itself is not a active substance, instead it must be first
converted through a succession of reaction in the liver and the kidneys
to the final active product 1, 25 di hydroxycholecalciferol
Action on bone:
In the osteoblasts of bone calcitriol stimulates ca uptake for
deposition as capo4
Action on kidney:
It is involved in minimizing the excretion of ca&p through
kidney by decreasing their excretion and enhancing
reabsorption
PARATHYROID HORMONE
Parathyroid hormone is one of the
main hormones controlling Ca
+2
absorption.
It mainly acts by controlling the
formation of 1,25 DHCC, which is
active form of Vit. D, which is
responsible for, increased Ca
+2
absorption.
NORMAL PTH LEVEL IN SERUM – 10-60ng/L
PARATHYROID HORMONE (PTH)
Secreted by parathyroid gland
Glands are four in number
Present posterior to the thyroid gland
Formed from third and fourth branchial pouches
Histologically – two types of cells
1)Chief cells (forming PTH)
2)Oxyphilic cells (replaces the chief cells
stores hormone)
ACTIONS OF PTH
The main function is to increase the level of Ca in plasma within
the critical range of 9 to 11 mg.
Parathormone inhibits renal phosphate reabsorption in the
proximal tubule and therefore increases phosphate excretion.
( Mg,H and Na,K)
Parathormone increases renal Calcium reabsorption in the distal
tubule, which also increases the serum calcium.
Net effect of PTH ↑ serum calcium
↓ serum phosphate
STIMULATION FOR PTH SECRETION
The stimulatory effect for PTH secretion is low level of calcium in
plasma. (Rapid phase,Slow phase)
Maximum secretion occurs when plasma calcium level falls below
7mg/dl.
When plasma calcium level increases to 11mg/dl there is decreased
secretion of PTH
CALCITONIN
Minor regulator of calcium & phosphate metabolism
Secreted by parafollicular cells or C-cells of thyroid gland.
Single chain polypeptide
Plasma concentration – 10-20ug/ml
Calcitonin is a Physiological Antagonist to PTH with respect to Calcium.
With respect to Phosphate it has the same effect as PTH i.e. ↓ Plasma
Phosphate level
ACTION OF CALCITONIN
Net effect of calcitonin
decreases Serum Ca
Target site
Bone (osteoclasts)
Kidney
Intestine
OTHER HORMONES ON CALCIUM METABOLISM
GROWTH HORMONE
INSULIN
TESTOSTERONE & OTHER HORMONES
LACTOGEN & PROLACTIN
STEROIDS
THYROID HORMONES
Influence of other harmones:
Increases the intestinal absorption of calcium and
increases its excretion from urine
Stimulates production of insulin like growth factor in
bone which stimulates protein synthesis in bone
GROWTH HORMONE
TESTOSTERONE
Testosterone causes differential growth of cartilage resulting to
differential bone development
Acts on cartilage & increase the bone growth.
INSULIN
It is an anabolic hormone which favors bone formation
THYROID HORMONE
In infants stimulation of bone growth
In adults
increased bone metabolism increased calcium mobilization
GLUCOCORTICOIDS
Anti vitamin D action, decrease absorption of calcium in
intestine
Inhibit protein synthesis and so decrease bone formation
Inhibit new osteoclast formation & decrease the activity of old
osteoclasts.
CONCEPT OF CALCIUM BALANCE
Defined as the net gain or loss of calcium by the body over a
specified period of time
Calculated by deducting calcium in faeces and urine from the
calcium taken in diet.
Positive calcium balance in growing children
Negative calcium balance in aging adults.
APPLIED ASPECT
OSTEOPOROSIS
An atrophy of bone
Bone resorption>bone deposition
Calcium or hormonal deficiencies
Older people- women>60yrs
c/f: loss of height- shortening of the trunk &collapse of the vertebrae
Deformed thoracic cage
Bone pain-due to fracture
Common causes:
Lack of physical stress
Lack of vitamin c
Post menopausal lack of estrogen
Old age
Cushing’s syndrome
Malnutrition
Radiographically:
loss of bone density
Thinning of cortex
Trabaculae-reduced
RICKETS
Softening of the bones in children potentially leading to fractures and
deformity.
Due to def. of vit.D causing deficiency in Ca & phosphate
CLINICAL FEATURES
Femoral and tibial bowing
Growth retardation
weakness
tetany
Susceptibility to fracture
Irritability
Some studies shown that rickets during the
time of tooth formation is the most
common cause of enamel hypoplasia.
Shelling & Anderson- in rachitic
children:43% of teeth showed hypoplasia.
Type- pitting variety
Plasma concentration of
calcium and phosphate
decrease in rickets:
Calcium is slightly
depressed(PTH)
Phosphate is greatly
depressed
Ricket weakness in bones:
Prolonged rickets
increased PTH
increased osteoclastic activity
rapid osteoblastic activity
TETANY IN RICKETS:
In early stage if rickets, tetany almost
never occurs
PTH activates osteoclastic absorption of
bone
<7ml/dl
Tetanic respiratory spasm
IV calcium
Oral manifestation:
Sir Edward Mellanby (1884-1955)- 1
st
to report the effect of
rickets on the teeth.
1.Development abnormalities of dentine & enamel,
2.Delayed eruption
3.Malalignment of the teeth in the jaws
4.High caries index
5.Abnormally wide predentine zone
6.Interglobular dentine
Many reports-rickets linked with hypoplasia
TREATMENT:
Diet and sunlight
Recommendations are for 400 international units (IU) of vitamin D a day for
infants and children. Children who do not get adequate amounts of vitamin D are at
increased risk of rickets. Vitamin D is essential for allowing the body to uptake
calcium for use in proper bone calcification and maintenance.
According to the American academy of paediatrics (AAP),
all infants, including those who are exclusively breast-
fed, may need Vitamin D supplementation until they
start drinking at least 17 US fluid ounces (500 ml) of
vitamin D-fortified milk or formula a day.
OSTEOMALACIA
Softening & distortion of skeleton
Oral manifestation:
Taylor & day-50% incidence of
severe periodontitis in a series of 22
Indian women
Oral manifestation:
Severe Periodontitis
Thin or absent trabeculae
Loosened teeth
Weakened jaw bones
Clinical features:
Bone pain and tenderness
Peculiar waddling or “penguin”gait
Tetany
Greenstick bone fractures
Myopathy
HYPOPHOSPHATASIA:
Def. of enzyme alkaline phophatase
Excretion of phosphoethanolamine in the urine
C/F:
Infantile form
Severe rickets
Bone abnormalities
Failure to thrive
Childhood
Loss of primary teeth
Increased infection
Growth retardation
Rachitic like deformation,
lung., renal, GI disorders
Adult
Spontaneous fracture
Oral manifestations:
Premature loss of primary teeth
Gingivitis
Radiographic features:
Hypocalcification
Large pulp chambers
Alveolar bone loss
HYPOCALCEMIA
<8.8 mg/dl
<8.5mg/dl- mild tremors
<7.5mg/dl- life threatening
condition will result- TETANY
Symptoms
muscle cramps
Paresthesia
Neuromuscular irritability
muscle twitching
Tetany
Seizures
Bradycardia
Causes
Hypoparathyroidism
Vit. D deficiency
Increased calcitonin
Deficiency of calcium, magnesium
Hypoalbuminemia
Trousseu’s sign
Treatment:
Oral calcium with vitamin d
supplementation.
Underlying cause should be
treated.
Tetany needs IV calcium.
Chvotske’s sign
MANAGEMENT OF HYPERCALCEMIA
Adequate hydration, IV normal saline
Furosemide IV to promote calcium excretion
Steroids, if there is calcitriol excess
Definitive treatment for the underlying disorder
PERIODONTAL DISEASE DUE TO DIETARY CALCIUM
DEFICIENCY AND/ OR DIETARY PHOSPHOROUS EXCESS
Henrickson suggested:
High incidence of periodontal disease in natives of India-attributed
in part to their low dietary calcium intake.
Labile for Resorption- Alveolar bone
Vertebrae
Ribs
Long bones
Nutrition and Immunology: Principles and Practice edited by M. Eric Gershwin, J. Bruce German, Carl L. Keen
CASE REPORT:
A 19-month-old girl was referred to a University of Minnesota pediatric dental clinic for consultation due to the unexplained,
nontraumatic, premature loss of the patient’s lower central incisors. At the initial consult, the patient presented with an
unremarkable medical history and was in good general health. She was growing along the 14th percentile for length and 34th
percentile for weight. She lost her first tooth at 10 months of age, and a second tooth at 12 months. At 15 months, she was
found to have four loose teeth. Although there was no family history of skeletal abnormalities, her maternal grandfather and
his mother started losing teeth in their 50s. The patient’s 6-year-old brother had no history of premature tooth loss.
Biochemical and Radiographic Evaluation — The patient’s vitamin D, intact parathyroid hormone, calcium
and phosphorus levels were all within normal range, however. In addition, her bone alkaline phosphatase
level was low (30.1 ug/L, compared to a normal range of 33.4 to 145.3 ug/L). Radiographic imaging showed
no skeletal abnormalities.
Oral Evaluation — Initial interpretation and assessment by a
general dentist attributed the premature loss of her first
primary incisor to unwitnessed orofacial trauma. After the loss
of her second primary incisor and presence of four loose
maxillary incisors, the patient was evaluated by a pediatric
dentist, who suspected HPP and referred her to a medical
provider. Subsequent evaluations of alkaline phosphatase levels
were also low at 18 months, and again two weeks later. She
subsequently exfoliated a third primary tooth — a lower lateral
incisor. The third exfoliated tooth was submitted to the
University of Minnesota Oral Pathology Laboratories for
histologic assessment. The lab confirmed a lack of cementum ,
which is consistent with a potential diagnosis of HPP.
EFFECT OF CALCIUM, PHOSPHORUS IMBALANCES &
VITAMIN D DEFICIENCY ON DENTAL CARIES INCIDENCE
Variation in Ca:P Ratios in experimental diets
Quite cariogenic, because the carbonate level of the tooth was
increased.
Relatively acid soluble
Highly susceptible to dental decay
SUMMARY
HARMONAL INFLUENCE
ON BLOOD CALCIUM
EFFECTS OF HARMONES
ON BLOOD PHOSPHATE
LEVELS
CONCLUSION
REFERENCES
1.Textbook of medical biochemistry-DM
Vasudevan
2.Textbook of medical physiology-Guyton and Hall
3.Textbook of medical physiology-Sembulingam
4.Essentials of biochemistry,Satyanarayan- 3
th