Bio chemistry important topic

1. Calcium-Phosphate
Metabolism
Guided by
DR. P. KARUNAKAR
DR. UMRANA FAIZUDDIN
DR. SHANTHI PRIYA
Presented by
SAIDEEP V CHADA
PG 1st year

2. Contents…
-INTRODUCTION
-CALCIUM REGULATION IN
BODY
-CALCIUM METABOLISM
-FACTORS REGULATING
CALCIUM METABOLISM
-TOOTH MINERALISATION
-PHOSPHOROUS
REGULATION IN BODY
-PHOSPHOROUS
METABOLISM
-FACTORS REGULATING
PHOSPHOROUS
METABOLISM
-APPLIED ASPECTS
-CONCLUSION
-REFERENCES
2

3. 3

5. What is Calcium…?
 Soft grey alkaline metal
 Essential for living organisms
 It is a divalent cation
 Atomic weight: 40g/mol
 Fifth most abundant element in the Earth’s crust.
5

6. Where did it come from…?
• In Latin, calx or calcis means ‘Lime’.
• Used since 1st century when ancient Romans prepared lime as
Calcium oxide.
• Isolated by Sir Humphrey Davy in 1808.
• Biological significance demonstrated by Sydney Ringer in 1883.
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7. 7
1% of TotalB
ody
Calcium

8. 8
-MOST ABUNDANT MINERAL OF OUR BODY-

9. 9
800mg
1200mg
360-540mg
800-1200mg
DAILY REQUIREMENTS OF
CALCIUM:
ADULT MALES AND FEMALES
WOMEN DURING PREGNANCY AND
LACTATION
INFAN.TSUNDER 1 YEAR
CHILDREN(1-18 YEARS)
Dietary calcium intake is inversely related to body weight and body fat
mass. It has the potential to increase faecal fat excretion to an extent that
could be relevant for prevention of weight (re-)gain.
(Nutrition Reviews. 66(10):601-605,
October 2007)

10. Where do we get it from…?
• Milk Products
• Eggs
• Meat, Fish
• Vegetables
• Fruits
• Nuts Eg.Almonds,Peanuts
• Bread (Fortified)
• Hard Water
10

11. CALCIUM REGULATION IN
THE BODY
11

12. Factors Increasing
absorption :
- Calcitriol
- Paratharmone
- Acidity (Low PH)
- Growth Hormone
- Pregnancy, Lactation
- Lactose, Arginine,Lysine
Factors Decreasing absorption :
- Oxalates & phytates – form Ca salts
-High dietary fats & fibers
-Phosphates
-Alkalinity
-Chronic renal failure ( impaired
activity of vitamin – D)
12

13. 13

14. 14

15. ABSORPTION& EXCRETION OF CALCIUM IN BODY
15
-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
-After oral administration absorption is completed
within 4hrs

16. INCREASED BY DECREASED BY
 Acidity in stomach
 Calcium-Phosphate ratio
 Hypocalcemia
during pregnancy &
lactation
 Vitamin D3- (1,25-DHCC)
 Parathyroid hormone
 Lactose
 Intestinal alkalinity
 Excess of oxalate
 Excess of phytic acid
 Hypercalcemia
 Fats
 Alcohol and smoking
 Lack of exercise
 Emotional stability
 Glucocorticoids
FACTORS AFFECTING CALCIUM ABSORPTION FROM GIT
16

17. EXCRETION
17
• As calcium is both filtered and reabsorbed but not
secreted, the rate of renal calcium excretion is
calculated as
• Renal calcium excretion= calcium filtered – calcium reabsorbed
-99% of filtered calcium (Glomerulus) is
reabsorbed by the tubules, 1% gets excreted
-65% is reabsorbed in proximal tubules, 25-30% in Loop of
Henle and 4-9% in distal and collecting tubules.
Daily loss of Calcium in sweat is about 15mg.

18. 18

19. 19

20. FACTORS CONTROLLING EXCRETION
• Calcium concentration in the body
• PTH (Loop of Henle and distal tubules)
• Plasma concentration of Phosphate
↓CALCIUM EXCRETION
↑ PTH
↓ Extracellular fluidvolume
↓ Bloodpressure
↑ Plasma phosphate
↑CALCIUM EXCRETION
↓ PTH
↑ Extracellular fluidvolume
↑ Blood pressure
↓ Plasma phosphate
20

21. HORMONES INFLUENCING CALCIUM
ABSORPTION
21
• GROWTH HORMONE
• “PROLACTIN (Prolactin has been shown to stimulate
intestinal calcium absorption, increase bone turnover, and
reduce renal calcium excretion)”
Canadian Journal of Physiology & Pharmacology. 85(6):569-581, June 2007)

22. FUNCTIONS OF CALCIUM
22
• Bone and teeth formation
• Neuronal activity
• Muscle activity
• Cardiac activity
• Cell division and growth
• Blood coagulation
• Excitability of nerves and muscles
• Maintains integrity of cell membrane

23. 23

24. -Constituent of bone and teeth-
24
• Calcium and phosphorous are the principal constituent
minerals of bone and teeth.
• They occur in the bone matrix, enamel, dentin and cementum of
teeth mainly as rod shaped or plate-shaped crystals of calcium
hydroxyapatites. These give the hardness, strength and concrete
like elastic modulus to these tissues

25. FACTORS REGULATING CALCIUM
METABOLISM
Parathyroid hormone
Vitamin D
Calcitonin
25

26. PARATHORMONE
26
-Secreted by Chief cells of parathyroid gland
-it provides a powerful mechanism for controlling extracellular calcium and
phosphate concentrations

27. On blood calcium level:
1. Increases bone resorption/absorbtion
2. Increases renal Ca ++ absorption in distal tubules
3. Increases absorption of intestinal Ca++
On blood phosphate level:
1. Stimulates resorption of phosphate from bone
2. Increases urinary excretion
3. Increases absorption of phosphate from GIT through calcitriol
ACTIONS OF PTH
27

28. ↓ BONERESORPTION
↑ URINARYLOSS
↓ 1,25,(OH)2D
PRODUCTION
↓
NORMAL BLOOD CALCIUM
↑
↑ BONERESORPTION
↓ URINARYLOSS
↑ 1,25,(OH)2 D
PRODUCTION
SUPPRESS PTH
RISING BLOOD CALCIUM
FALLING BLOOD
CALCIUM
STIMULATE PTH
28

29. Role of PTH in the activation of VITAMIN D
29
VITAMIN D IS A HORMONE BY CLASSIC CRITERIA: MADE IN
ONE PLACE (OR SEQUENTIALLY SEVERAL PLACES!), AND
ACTING IN OTHER
(400
DAILY DIETARY ALLOWANCE RECOMMENDED:
-From infancy till puberty is 10 mcg of cholecalciferol IU of
vitamin D)
-In young adulthood, its 7.5 mcg
-After 25 yrs, 5 mcg required
Pregnancy and lactation 10 mcg

30. 30
ACTIVATION OF VITAMIN D

31. BONE
STIMULATE TERMINAL DIFFERENTIATION OF
OSTEOCLASTS
STIMULATE OSTEOBLASTS TO STIMULATE
OSTEOCLASTS TO MOBILIZE CALCIUM
KIDNEY
IT INCREASES RE-ABSORPTION OF Ca FROM DCT &
INCREASES RE-ABSORPTION OF PHOSPHATE ION
FROM PCT
31

32. ACTIONS OF 1,25-Dihydroxycholecalciferol
1.Increases absorption of Ca from intestine
2.Increases synthesis of Ca induced ATPase in the
intestinal epithelium
3.Increases synthesis of alkaline phosphatase in the
intestinal epithelium
4.Increases absorption of phosphate from intestine.
32

33. CALCITONIN
33
• It is a 32 amino – acid polypeptide, secreted from clear cells or
parafollicular cells of thyroid glands therefore also, known as
THYROCALCITONIN
• It is not secreted until the plasma calcium exceeds
9.5mg/dl
• Normal secretion is 0.5mg/day;
• half life less than 15 mins;
• molecular weight 3000;
Normal plasma level 0.2ngm/ml

34. ACTIONS:
34
4
Ca++and PO --
ON BLOOD CALCIUM LEVEL-
It reduces the blood calcium concentration
ON BONE
Stimulates osteoblastic activity
Inhibits osteoclastic activity
ON KIDNEYS
Increases excretion of Ca through urine
Inhibits reabsorption of Ca from renal tubules
ON GIT
Inhibits intestinal absorption of

35. PTH 1,25-DHCC CT
ON BONE Bone resorption
increases
Mobilize Ca &
P
Bone resorption
decreases
ON GIT Ca & P absorption
increases
Ca & P
absorption
increases
Ca & P absorption
decreases
ON KIDNEY P absorption
decreases
Ca reabsorption
increases
Ca resorption
increases
1,25-DHCC
decreases
Ca & P excretion
increases
ON S.Ca+2 Increases Increases Decreases
ON S.PO4-3 Decreases Increases Decreases
35

36. Applied Physiology
36
Disorders of parathyroid glands ( two types )
1.HYPOPARATHYROIDISM
-causes: Parathyroidectomy
Thyroidectomy
Deficiency of receptor for PTH
1.HYPERPARATHYROIDISM
Primary hyperparathyroidism
Secondary hyperparathyroidism
Tertiary hyperparathyroidism

37. Hypoparathyroidism- Hypocalocemia
Hypocalcemic tetany:
Signs and Symptoms
1. Hyper-reflexia and convulsions
2. Carpopedal spasm
3. Laryngeal stridor
4. Cardiovascular changes
5. Other features
Late or subclinical tetany:
1. Trousseau’s sign
2. Chvostek’s sign
3. Erb‘s sign
37

38. Hyperparathyroidism- hypercalcemia
Signs and Symptoms:
1. Depression of the nervous system
2. Sluggishness of reflex activities
3. Reduced ST segment and QT interval in ECG
4. Lack of appetite
5. Constipation
Parathyroid function tests:
Measurement of blood Ca level
Chvostek’s sign and Trousseau’s sign for Hypoparathyroidism
38

39. CALCIUM AND DENTAL CARIES
39
If it occurs when teeth are still forming, following
abnormalities may occur:
-Enamel hypoplasia
-Poorely mineralised dentin
-Malformed teeth
-Elongated pulp chambers
-Anodontia or impacted teeth

40. CALCIUM AND SALIVA
40
• Calcium content of submandibular saliva is almost doublethe
parotid content. This probably contributes to marked prevalence
of calculus on lingual aspect of mandiblular incisors
• Concentration of calcium lessens as salivary flow increases. This
probably results from the increased parotid contribution in rapid
salivary flow rates
-Principal salivary calcium phosphates salts are dicalcium
phosphate dihydrate, octacalcium phosphate, tricalcium
phosphate and hydroxyapatite

41. • Key element in all the known forms of life
• Plays a major role in biological molecules such as RNA and DNA
• Main structural component of all the cellular membranes
• Living cells also utilize phosphate to transport cellular energy via
ATP
• Average person contains little less than 1 kg of phosphorous,
about 3 quarters present in bones and teeth in form of Apatite
crystals
41

42. It is found in ATP, cAMP, 2, 3-DPG (diphosphoglyceric
acid)
Total body phosphate is 500-600gms,
80-85% is in skeleton
Remaining is in intracellular phosphate pool.
Serum inorganic phosphate level:
In adults: 2.5-4mg%
In children: 5-6mg%
42
Phosphate Metabolism

43. Adequate Intake
•0-6 months
•6-12 months
100 mg/day
275 mg/day
Estimated Average Requirements
380 mg/day
405 mg/day
1,055 mg/day
•1-3 years
•4-8 years
•9-18 years
•19-70+ years
•Pregnant &
lactating women
580 mg/day
Same as for nonpregnant &
nonlactating women
Reference: Dietary Reference Intakes, Food and Nutrition Board,
National Academy of Sciences-Institute of Medicine, 1997
43
How much do we need…?

44. Total phosphate:500-800 mg
44
Bones and teeth
80-85%
Inorganic
(Adults:3-4mg/dl)
(children:5-6mg/dl)
Normal plasma levels:
2.5-4.5 mg/dl
Organic
(0.5-
1mg/dl)
Distribution

45. Approximately 3mg/kg/day of Phosphorous enters the bone
.
In plasma it is filtered in glomeruli of which 85-95% gets
reabsorbed actively in PCT. Its excretion in urine is:
INCREASEDBY: DECREASEDBY:
Vitamin Dexcess; GH,duringlactation;
hyperparathyroidism; hypoparathyroidism;
high phosphatediet. low phosphatediet.
45
Distribution and Fate

46. 46
Gives rigidity to bones and teeth
Helps in regulation of pH of blood
In regulation of glycolysis and energy
metabolism
Forms a part of DNA, RNA, Phospholipids &
nucleotides.
Functions…

47. 47

48. Overview of Phosphate Balance
48

49. Conditions arising from
disruption / irregularities of
phosphate metabolism
49

50. Etiologies of Hyperphosphatemia
50
Increased GI Intake :
(Fleet’s Phospho-Soda)
Decreased Urinary Excretion :
Renal Failure
Low PTH (hypoparathyroidism)
Thyroidectomy
Autoimmune
hypoparathyroidism
Cell Lysis :
Rhabdomyolysis
Tumor lysis syndrome

51. Etiologies of Hypophosphatemia
51
Decreased GI Absorption
Decreased dietary intake
Diarrhea / Malabsorption
Phosphate binders (calcium acetate, Al & Mg
containing antacids)
Decreased Bone Resorption / Increased Bone Mineralization
Vitamin D deficiency / low calcitriol
Hungry bones syndrome
Osteoblastic metastases

52. Increased Urinary Excretion
Elevated PTH (as in primary hyperparathyroidism)
Vitamin D deficiency / low calcitriol
Fanconi’s syndrome
Internal Redistribution (due to acute stimulation of
glycolysis)
Refeeding syndrome (seen in starvation, anorexia, and
alcoholism)
During treatment for Diabetic keto acidosis
52

53. Applied Physiology
53

54. Rickets
54

55. Dental findings in Rickets
55
Rickets causes
hypoplasia or
hypocalcification

56. Pigeon Chest Deformity
56
Rachitic rosary

57. OSTEOMALACIA OR ADULT RICKETS
57
• The amount of mineral accretion in bone per unit bone matrix is
deficient due to inadequate absorption of Ca and decreased
amount of phosphorous owing to deficiency of vitamin D&C in
diet.
• Disease is limited to females, usually after multiple pregnancies
&lactation but symptoms tend to clear up after lactation is
completed.
• The bones especially pelvic girdle, ribs & femur become soft,
painful & deformed.

58. 58

59. 59

60. PSEUDOHYPOPARATHYROIDISM
60
The patients have normal parathyroid glands, but they fail to
respond to parathyroid hormone or PTH injections
Autosomal dominant
Symptoms and signs
Hypocalcemia
Hyperphosphatemia
Characteristic physical appearance: short stature, round face,
short thick neck, obesity, shortening of the metacarpals
Resistance to parathyroid hormone

61. PSEUDOHYPOPARATHYROIDISM
61
Pseudohypoparatyhroidism- induced dental anomalies
-ENAMEL HYPOPLASIA
-DENTIN DYSPLASIA
-SHORT BLUNTED ROOTS
-IMPACTED TEETH
-ALTERED TOOTH ERUPTION PATTERN
-PARTIALANODONTIA
Elfin facies

62. OSTEOPOROSIS
62

63. 63

64. OSTEOPOROSIS
64

65. PRIMARY HYPERPARATHYROIDISM
65
• Women (especially postmenopausal) are more commonly affected
than men (Scutellari et al, 1996).
• Causes
– SPORADIC ADENOMA(s) MOST COMMON CAUSE
– MULTIPLE ENDOCRINE NEOPLASIA TYPE 1 (MEN-1):
PARATHYROID TUMORS (AND PITUITARY AND PANCREAS)
– MEN-2a: PARATHYROID TUMORS, MEDULLARY THYROID
CANCER (OR HYPERPLASIA), AND PHEOCHROMOCYTOMA
1o
– FAMILIAL HYPERPARATHYROIDISM: HPT WITHOUT
THE OTHER TUMORS SEEN IN MEN-1 OR MEN-2a
– FAMILIAL BENIGN HYPOCALCIURIC
HYPERCALCEMIA

66. Characterized by:
66
• ↑ serumCa2+
• ↓ serumphosphate
• ↑ urinary phosphate excretion (phosphaturic effect ofPTH)
• ↓ urinary Ca2+ excretion (caused by ↑ Ca2+reabsorption)
• ↑ urinary (nephrogenous)cAMP
• ↑ bone resorption
• Osteoblastic activity increases in an attempt to make for the
resorbed bone. They secrete large quantities of alkaline
phosphatase

67. Clinical features
67
“Painful Bones, Renal Stones, Abdominal Groans,
Psychiatric Moans”
• Pain Due To # Of Bones
• Renal Stones (Nephrolithiasis) With Pain And Obstructive Uropathy
• GI Disturbances -Constipation, Pancreatitis, Nausea, PepticUlcrs
• CNS Alterations Including Depression, Lethargy And Seizures
• Neuromuscular Abnormality Including Weakness And Hypotonia

68. • Metastatic calcifications seen in subcutaneous soft tissues,
sclera, dura and region around joints
• Brown‘s tumor
• Affect mandible, clavicles, ribs and pelvis
• Osteitis fibrosa cystica- develops from central degeneration and
fibrosis of long standing brown tumor
68

69. Brown‘s Tumour
69

70. Dental Features of Browns Tumour
70

71. Radiological features
71
• First radiological sign is subperiosteal resorption of
phalanges of index and middle fingers
• Unilocular or multilocular cystic radiolucencies in bone
• Generalized Attenuation or loss of lamina dura surrounding the
teeth
• Decrease in trabecular density and blurring of normal
trabecular pattern, giving ‘Ground Glass’appearance

72. Granularappearanceof
skull inpatienthaving
renal osteodystrophy
72
Solitary“punchedout”
radiolucencyincalvarium
representsaBrown
tumourin secondary
hyperparathyroidism

73. Metastaticcalcificationsinhandand wristof
patientwithprimaryhyperparathyroidism
73
Calcificationofthethumb
Generalized Loss Of Lamina Dura

74. 74

75. Osteitis fibrosa cystica: Multilocular
radiolucencies in skull
75
Treatment:
• Hyperplastic parathyroid tissue or
functional tumor is removed surgically
to reduce PTH levels to normal

76. SECONDARY HYPERPARATHYROIDISM
76
• Secondary hyperparathyroidism results in excess secretion of
parathyroid hormone due to parathyroid hyperplasia
compensating for a metabolic disorder that has resulted in
retention of phosphate or depletion of the serum calcium level
(Ganibegovic, 2000).
• Renal osteodystrophy refers to skeletal changes that result from
chronic renal failure

77. • In patients with secondary hyperparathyroidism caused by end stage
renal disease, striking enlargement of jaw occurs
Palatalenlargementisacharacteristicofrenal osteodystrophy
associatedwithsecondary hyperparathyroidism
77

78. • Bone lesions in digits, clavicle
• Mottling of skull, erosion of the distal clavicle, rib fractures and
necrosis of femoral head.
• Children show osteomalacia
78

79. Treatment:
79
• Restriction of dietary phosphate
• Use of phosphate binding agents (calcium carbonate or calcium
acetate)
• Use of calcimimetic agents like cinacalcet
(Nephrol Dial Transplant (2002) 17: 204-207)
• Treatment with an active vitamin D metabolite
• Synthetic salmon calcitonin can be used
• Renal transplant: An ideal treatment

87. REFERENCES
• Textbook of Medical Physiology by Guyton & Hall; 10th Edition
• The Physiology & Biochemistry of the mouth by G.Neil Jenkins; 4th
Edition
• Textbook of Physiology by Prof.A. K. Jain
• Textbook of Endodontics – Ingle
• Textbook of Biochemistry- Dr.U.Satyanarayana
• Journal of Nutrition,Canada (2007)
• Dietary Reference Intakes, Food and Nutrition Board, National
Academy of Sciences-Institute of Medicine, 1997
• Canadian Journal of Physiology & Pharmacology. 85(6):569-581, June
2007)
• Nutrition Reviews. 66(10):601-605,
October 2007
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