Calcium and phosphate metabolism

1. CALCIUM AND
PHOSPHATE
METABOLISM

2. CONTENTS
• Introduction
• Important minerals
• Calcium & phosphorous metabolism
• Hormones involved in calcium and phosphate homeostasis
• Diseases
• Summary
• Conclusion
• References

3. INTRODUCTION
BALANCED DIET
METABOLISM
IMPORTANT MINERALS
Healthy Diet- Healthy Life

4. IMPORTANT MINERALS
Major 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.

5.  Most common metal 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

6. Phosphorus –
Due to its use in explosives, poisons -"the Devil's element".
In human body Phosphorus is present as phosphates (compounds
containing the phosphate ion, PO4
−3
)
 The first form of elemental phosphorus to be produced (white
phosphorus, in 1669) by Greek .
Hennig Brand(1669) discovered.

7. 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 (Ca10(PO4)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
Stimulation of muscle
action potential is
generated
Contraction of muscle

8. 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.

9. 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

10. 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)

11. DAILY REQUIREMENTSDAILY REQUIREMENTS
Calcium:
Adults
Pregnancy
Lactating mother
Infants
Children
Phosphates:
Adults
Pregnancy, lactation &
children
 Infants
500-800mg
1500mg
2000mg
360mg
800mg
1200mg
240mg
800mg
FAO/WHO Expert Group. 1962. Calcium Requirements. Rome, FAO

12. 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.

13. SOURCES OF CALCIUM
Calcium is present in variable amounts in all the foods
and water we consume, although the main sources
are dairy products and vegetables.

14. Milk-good sources of calcium
Calcium content of cow’s milk- 100mg/ml
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
osteoporosis-Women> men
Post menopause women start to lose more bone
Pregnant and breast feeding women must intake
adequate amount as the baby relies on only her
mother to get his supply of calcium.
A child with early childhood caries, in whom diet
management has to be considered. Milk with sugar
can be replaced (with flavoured lassi or a custard
pudding or kheer) rather than total stoppage of milk.

15. 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

16. Absorption of Calcium
Absorbed from the gastrointestinal tract in to blood
Two mechanisms have been proposed for the absorption
of calcium
→ Active absorption(Proximal portion of the duodenum
→ Passive absorption(In the remainder of the small intestine)

17. PHOSPHORUS ABSORPTION
 50-70%- absorbed
 Small intestine- soluble inorganic phosphate
 Excess calcium, iron or aluminum- interferes absorption

18. FACTORS CONTROLLING ABSORPTION
Factors are classified into
1. Those acting on the mucosal cells
2. Those affecting the availability of
calcium and phosphates in the gut.

19. Amount of dietary calcium and
phosphates:
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

20. • During later stages of pregnancy, greater amount
of calcium absorption is seen.
• 50% of this calcium is used for the development of
fetal skeleton and the rest is stored in the bones to
act as a reserve for lactation.
• This is due to the increased level of placental
lactogen and estrogen which stimulates
increased hydroxylation of vitamin D.
• In growth there is a increased level of growth hormone.
GH acts by increasing calcium absorption. It also
increases the renal excretion of calcium and
phosphates.
Pregnancy and growth:
The rise in maternal obesity highlights that maternal and newborn
vitamin D deficiency will continue to be a serious public health
problem until steps are taken to identify and treat low 25(OH)D.
Bodnar LM, Catov JM, Roberts JM, Simhan HN. Prepregnancy obesity predicts
poor vitamin D status in mothers and their neonates. The Journal of nutrition.
2007 Nov 1;137(11):2437-42.

21. HORMONAL CONTROL OF CALCIUM & PHOSPHATE
METABOLISM
Three hormones regulate calcium and
phosphate metabolism.
 Vitamin D
 PTH
 Calcitonin

22. Vitamin D
Cholecalciferol / D3
Ergocalciferol / D2
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,

23. VITAMIN-D(sun-shine vitamin)
Studies conducted by Cheng et al,2003 and Strushkevich et al in
2008 suggested that Vitamin D is converted in the liver to
25(OH)D, a process carried out by CYP2R1.
The crystal structure of CYP2R1 has been determined with vitamin
D in the active site, and the enzyme has been shown to
metabolize both vitamin D2 and vitamin D3 equally efficiently.

24. 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

25. Dietary sources
 Cod liver oil
 Fish- Salmon
 Egg, liver
Mean action of vitamin D is to increase the plasma level of
calcium.
Increases intestinal Ca&P absorption.
Increases renal reabsorption of Calcium and
phosphate.

26. Daily requirement
1)Children:10 mug/d(400iu)
2)Adults:5-10mug/d(200iu)
3)Pregnancy and lacation:10mug/d
4)Elderly:600iu/d
The new 2010 recommended daily allowance (RDA)

27. 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
Combined weight of 130mg with each gland weighing between 30-
50mg.
Histologically – two types of cells
Chief cells (forming PTH)
Oxyphilic cells (replaces the chief cells
stores hormone)

28. • 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

29. Parathyroid Hormone
 Single chain polypeptide
 Molecular weight 9000
 Consist of 84 amino acids
 Plasma half life – 20-30 minutes
 Plasma concentration – 10-50ug/ml
 Measured by immunoassay .

30. Actions of PTH
 The main function is to increase the level of Ca in
plasma within the critical range of 9 to11 mg.
 Parathormone inhibits renal phosphate reabsorption in
the proximal tubule and therefore increases phosphate
excretion
 Parathormone increases renal Calcium reabsorption in
the distal tubule, which also increases the serum calcium.
 Net effect of PTH  ↑ serum calcium
↓ serum phosphate

31. Stimulation for PTH secretion
 The stimulatory effect for PTH secretion is low level
of calcium in plasma.
 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

32. CALCITONIN
 Minor regulator of calcium & phosphate
metabolism
 Secreted by parafollicular cells or C-cells of
thyroid gland.
 Also called as thyrocalcitonin.
 Single chain polypeptide
 Molecular weight 3400
 Plasma concentration – 10-20ug/ml

33. Action of Calcitonin
Net effect of calcitonin  decreases Serum Ca
Target site
Bone (osteoclasts)
Kidney
Intestine

34.  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

35. OTHER HORMONES on CALCIUM
METABOLISM
GROWTH HORMONE
INSULIN
TESTOSTERONE & OTHER HORMONES
LACTOGEN & PROLACTIN
STEROIDS
THYROID HORMONES

36. 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

37. 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

38. Thyroid Hormone
 In infants  stimulation of bone growth
 In adults
increased bone metabolism  increased calcium
mobilization

39. 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.

40. Factors affecting availability of Calcium and
Phosphates in gut.
pH of the intestine
Amount of dietary calcium and phosphates
Phytic acid and Phytates
Oxalates
Fats
Proteins and amino acids
Carbohydrates
Bile salts

41. 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

42. 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.
Xiao et al(2010) have demonstrated that a duodenal
oxidation state induced by a high fat diet could significantly
down regulate the expression of CB9k, PMCA1b, and NCX,
as well as inhibiting intestinal calcium absorption.
They demonstrated that type diabetes mellitus transientlyⅠ
inhibits intestinal Ca2+ absorption.

43. 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.

44. 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.

45. Excretion of Calcium and
Phosphorous
 Calcium is excreted in the urine, bile, and digestive
secretions.
 The renal threshold for serum ca is 10 mg/dl.
 70-90% of the calcium eliminated from the
body is excreted in the feces.
 The daily loss of calcium in sweat is about 15 mg.
While passing through the kidney, large quantity of
calcium is filtered in the glomerulus. From the
filtrate, 98 to 99% of calcium is reabsorbed in the
renal tubules in to blood and only small quantity is
excreted through urine.

46. Daily turnover rates of Ca in an adult are as
follows:
Intake 1000mg.
Intestinal absorption 350mg
Secretion in GI juice 250mg
Net absorption over secretion 100mg
Loss in the faeces 200mg
Excretion in the urine 80-100mg

47. Phosphorous Excretion
Phosphorous is excreted primarily through the urine.
Almost 2/3rd
of 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.

48. 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
• Radiographically: loss of bone density
Thinning of cortex
Trabaculae-reduced

49. ASSOCIATION OF MENOPAUSE,
OSTEOPOROSIS AND
PERIODONTAL DISEASES
OSTEOPOROSIS &
PERIODONTAL DISEASE
>40yrs-decline in the estrogen levels due to decrease
in the ovarian functions.
All these hormonal changes will lead to
psychological, oral and systemic health changes.
Oral changes that can be seen may include: thinning
of oral mucosa, desquamation of gingival epithelium,
burning mouth, gingival recession, xerostomia and
alveolar bone loss & ridge resorption
Since both osteoporosis and
periodontal diseases are bone
resorptive diseases,
It has been hypothesized that
osteoporosis could be a risk factor for
the progression of periodontal disease
Heaney et al(2011)-comparison of pre and post-menopausal women found
that calcium balance fell significantly in post-menopausal women and that
this was due to both a reduction in calcium absorption and an increase in
urinary calcium loss.

50. 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
Longo, Dan L. et al. (2012). Harrison's principles of internal medicine. (18th
ed. ed.). New York: McGraw-Hill. ISBN 978-0-07174889-6.

51. Oral manifestation:
Sir Edward Mellanby (1884-1955)- 1st
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

52. 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.
Gartner LM, Greer FR (April 2003). "Prevention of rickets and vitamin D deficiency: new guidelines for
vitamin D intake". Pediatrics. 111 (4 Pt 1): 908–10.

53. • A female, aged 2 years and 6 months, was referred by her general dentist to British Columbia's Children's
Hospital dental department with facial pain and swelling. Oral antibiotics had been prescribed and the
symptoms were improving when the child was first seen
• Preoperative assessment by the pediatrician revealed a waddling gait, and a hip radiograph (not shown)
showed normal acetabular angles, metaphyseal lucency, and medial beaking. Hemoglobin was within
normal limit
• clinical examination confirmed a complete primary dentition and a discharging sinus in the buccal sulcus
associated with the carious maxillary right primary first molar. Carious lesions were noted in the
following teeth: all maxillary primary incisors, all primary first molars, and the mandibular primary
central incisors.
• The medical, hematological, and radiological investigations reported nutritional rickets.
• Intraoral dental radiographs (Fig 1) illustrate the extent of the carious lesions and the large size of the
pulp chambers with pulpal horn extension close to the dentoenamel junction, especially in the
mandibular primary first molars. Hypoplasia was not evident in the unerupted teeth. The bone
trabeculation in the anterior mandible and maxilla was very sparse. The lamina dura and the crypts of
the developing teeth were present, but attenuated. On the left side, the cortices of the inferior alveolar
canal were evident and the inferior cortex of the mandible appeared thinned, but the other side was not
available for comparison
• Oral vitamin D and Calcium Sandoz (Sandoz Canada Inc., Dorval, QB) were prescribed. An initial drop in
the serum calcium level was easily corrected by adjusting the medication.
Nutritional rickets in a 2-year-old child: case report Donal McDonnell, BDS, FFD, MSc,
FRCD(C) Gary Derkson, DMD

54. OSTEOMALACIA
 Softening & distortion of skeleton
 Oral manifestation:
Taylor & day-50% incidence of severe periodontitis in a
series of 22 Indian women
Clinical features
Bone pain and tenderness
Peculiar waddling or “penguin”gait
Tetany
Greenstick bone fractures
Myopathy

55. ORAL MANIFESTATION:
Severe Periodontitis
Thin or absent trabeculae
Loosened teeth
Weakened jaw bones

56. HYPOPHOPHATASIA
• 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

57.  Oral manifestations:
Premature loss of primary teeth
Gingivitis
 Dental roentgenogram:
Hypocalcification
Large pulp chambers
Alveolar bone loss

58. 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

59. TETANY
Manifestations: Carpopedal spasm
Laryngismus stridor
Chvostek’s sign Trousseu’s sign
Treatment:
Oral calcium with vitamin d
supplementation.
Underlying cause should be treated.
Tetany needs IV calcium.

60. HYPERCALCEMIA
Causes
•Hyperparathyoidism
•Thyrotoxicosis, addison’s disease
•Paget’s disease
•Dehydration
•Tb, leprosy
•Milk- alkali syndrome
•Drugs- thiazides
symptoms
•Anorexia, nausea, vomiting
•Polyuria, polydypsia
•Confusion, depression, psychosis
•Osteoporosis & pathological fracture
•Renal stones
•Ectopic calcification & pancreatitis
•Increased serum alkaline phosphatase

61.  Adequate hydration, IV normal saline
 Furosemide IV to promote calcium excretion
 Steroids, if there is calcitriol excess
 Definitive treatment for the underlying disorder
MANAGEMENT OF HYPERCALCEMIA

62. 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

63.  Lutwak et al- demineralization of alveolar bone in humans
was reversed by daily dietary calcium supplements over a
period of a year.
 Hypothesized: periodontal bone loss was a direct result of
calcium deficient diet leading to secondary
hyperparathyroidism and the reversal of this condition is by
dietary calcium supplements
Journal of PeriodontologyOctober 1974, Vol. 45, No. 10, Pages 739-745 , DOI 10.1902/jop.1974.45.10.739 (doi:10.1902/jop.1974.45.10.739)

64. 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

65. NUTRITIONAL FACTORS ASSOCIATED WITH DENTAL
ENAMEL HYPOPLASIA
 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

66. SUMMARY

70. CONCLUSION

71. REFERENCES
1. Textbook of medical biochemistry-DM
Vasudevan
2. Textbook of medical physiology-Rodney
3. Textbook of medical physiology-Sembulingam
4. Harper’s biochemistry- 25th
edition
5. Shafer’s oral pathology- 5th
edition
6. Internet sources