3. INTRODUCTION
Hundreds of reactions simultaneously take place in a living cell, in a well-organised and
integrated maanner.
The entire spectrum of chemical reactions, occuring in the living system, are collectively
reffered to as metabolism.
The term metabolite, is applied to a substrate or an intermediate or a product in the
metabolic reactions.
Metabolism is broadly divided into two categories.
1) Catabolism and
2) Anabolism.
4. INTRODUCTION
1) Catabolism: The degradative processses
concerned with the breakdown of complex
molecules to simpler ones, with a concomitant
release of energy.
2) Anabolism: the biosynthetic reactions
involving the formation of complex molecules from
simple precursors.
5. CALCIUM
Calcium is the most abundant among the minerals in the
body.
Calcium regulation can be explain using RULE OF 3
1) Three tissues: BONE, INTESTINE,KIDNEY
2) Three hormones: PTH, CALCITONIN AND VITAMIN D3
3) Three cell types: OSTEOBLASTS, OSTEOCYTES AND
OSTEOCLAST
7. DAILY REQUIREMENTS
ADULT MEN AND WOMEN- 800 mg/ day
WOMEN DURING PREGNANCY,
LACTATION AND - 1.5 g/ day
POST MENOPAUSE
CHILDREN (1-18yrs) - 0.8-1.2 g/day
INFANTS(< 1 YEAR) - 300-500 mg/day
8. DIETARY SOURCE
BEST SOURCES - MILK AND MILK PRODUCTS
GOOD SOURCES- BEANS, LEAFY VEGETABLES, FISH,
CABBAGE, EGG YOLK.
9. FUNCTIONS
1) DEVELOPMENT OF BONES AND TEETH
a) Calcium along with phosphate, is requried for the formation( of
hydroxyapatite) and physical strength of skeletal tissue.
b) Osteoblast are responsible for bone formation while osteoclasts result in
demineralaization.
10. FUNCTIONS
2) MUSCLE
A) Calcium mediates EXCITATION AND CONTRACTION of muscle fiber.
b) Calcium activates ATPase: increases action of actin and myosin and facilates
excitation-contraction coupling.
c) Calcium decreases neuromuscular irritability.
d) calcium deficiency causes tetany.
11. FUNCTIONS
3) BLOOD COAGULATION
a) Calcium is known as foctor IV in blood coagulation cascade.
4) NERVE TRANSMISSION
a) ca2+ is necessory for the transmission of nerve impulse.
5) MEMBRANE INTERGRITY AND PERMEABILITY
a) Ca2+ influences the membrane structure and transport of water and several ions across it.
6) ACTIVATION OF ENZYMES
a) Ca2+ is needed for the direct activation of enzymes such as lipase( pancreatic), ATP ase and succinate
dehydrogenase.
12. FUNCTIONS
7) CALCIUM AS INTRACELLULAR MESSENGER
a) Certain hormones exert their action through the mediation ofCa2+( Instead
of cAMP).
b) Calcium is regarded as a second messenger for such hormonal action e.g.
epinephrine in liver glycogenolysis.
C) Calcium serves as a third messenger for some hormones e.g antidiuretic
hormone acts through cAMP, and then ca2+
13. FUNCTIONS
8) MYOCARDIUM:
A) Ca++ PROLONGS SYSTOLE.
B) In hypercalcemia, Caediac arrest is seen in systole.
C) This fact should be kept in mind when calcium is administrated intravenously.
D) It should be given very slowly.
9) RELEASE OF HORMONES
A) The release of certain hormones( insulin, PTH, calcitonin) from the endocrine
glands is facilitated by ca2+
14. ABSORPTION
The absorption of calcium mostly occurs in the
duodenum by an energy dependent active process.
It is influenced by several factors
1) Factors promoting Ca absorption
2) Factors inhibiting Ca absorption
15. ABSORPTION
FACTORS PROMOTING Ca absorption
1) Vitamin D ( through the active form calcitriol) induces
the synthesis of calcium binding protien in the intestine
epithelial cells and promotes Ca absorption.
2) parathyroid hormone enhances Ca absorption through
the increased synthesis of calcitriol.
3) Acidity( low PH) is more favourable for Ca absorption.
16. ABSORPTION
FACTORS PROMOTING Ca absorption
4) Lactose promotes calcium uptake by intestinal cells.
5) The amino acids lysin and arginine facilates Ca
absorption.
17. ABSORPTION
FACTORS INHIBITING Ca absorption
1) Phytates and oxalates form insoluble salts and interfere
with Ca absorption.
2) High content of dietary phosphate results in the
formation of insoluble calcium phosphate and prevent Ca
uptake. The dietary ration of Ca and P between 1:2 and
2:1 is ideal for optimum Ca absorption by intestinal cells
18. ABSORPTION
FACTORS INHIBITING Ca absorption
4) Alkaline condition (high PH) is unfavourable for Ca
abosrption.
5) Higher content of dietary fiber interferes with Ca
absorption.
19. PLASMA CALCIUM
Normal concentration of plasma or serum Ca is
9-11 mg/dl.
At least 1mg/dl serum Ca is found in association
with citrate and or phosphate
The other half of serum Ca ( 4-5 mg/dl ) is bound
to protiens, mostly albumin and, to a lesser
extend, globulin.
20. FACTORS REGULATING PLASMA CALCIUM LEVEL
The major factors that regulate the plasma calcium within a narrow range
Vitamin D
Calcitriol
Parathyroid hormone and
Calcitonin .
23. FACTORS REGULATING PLASMA CALCIUM LEVEL
Calcitriol
1) Active form of vitamin D is a hormone, namely calcitriol or 1,25- dihydroxy-cholecalciferol.
2) Its main action is to increase the blood calcium level by increasing the calcium absorption
from the small intestine.
3) Furthermore, Calcitriol stimulates calcium uptake by osteoblasts of bone and promotes
calcifications or mineralization( deposition of calcium and phosphate) and remodelling.
24. FACTORS REGULATING PLASMA CALCIUM LEVEL
PARATHYROID HORMONE
1) It is a protein hormone secreted by parathyroid gland.
2) Molecular weight is 95,000 is a single chain polypeptide,
containing 84 amino acids
2) Its main function is to increase the blood calcium level.
25. FACTORS REGULATING PLASMA CALCIUM LEVEL
MECHANISM OF ACTION OF PTH
1) PTH binds to a membrane receptor protein on the target cell and activates
adenylate cyclase to liberate c AMP.
2) This, in turn, increases intracellular calcium that promotes the phosphorylation
of proteins which, finally brings about the biological actions.
3) PTH has three independent tissues
Bone
Kidneys and
Intestine
4) The PRIME FUNCTION OF PTH IS TO ELEVATE SERUM CALIUM
LEVEL.
27. FACTORS REGULATING PLASMA CALCIUM LEVEL
MECHANISM OF ACTION OF PTH
ACTION ON BONE:
1) PTH causes decalcification or DEMINERALIZATION OF BONE , a process
carried out by OSTEOCLAST.
2) This is brought out by PTH stimulated increased activity of the enzymes
pyrophosphatase and collagenase.
3) These enzyme result in bone resorption. Demineralization ultimately leads to an
increase in the blood Ca level.
4) The action of PTH on bone is quantitatively very significant to maintain Ca
homeostasis.
28. FACTORS REGULATING PLASMA CALCIUM LEVEL
MECHANISM OF ACTION OF PTH
ACTION ON KIDNEY:
1) PTH increases the Ca reabsorption by kidney tubules.
2) This is the most rapid action of PTH to elevate blood Ca levels.
3) PTH promotes the production of calcitriol in the kidney by stimulating 1
hydroxylation of 25 hydroxycholecalciferol.
29. FACTORS REGULATING PLASMA CALCIUM LEVEL
MECHANISM OF ACTION OF PTH
ACTION ON INTESTINE:
1) The action on PTH on intestine is indirect.
2) It increases the intestinal absorption of Ca
by promoting the synthesis of CALCITRIOL.
30. FACTORS REGULATING PLASMA CALCIUM LEVEL
MECHANISM OF ACTION OF PTH
CALCITONIN
1) It is a peptide containing 32 aminoacids.
2) It is secreated by parafollicular cells of thyroid gland.
3) Calcitonin promotes calcification by increasing the activity of osteoblasts.
4) Further, calcitonin decreases bone resorption and increases the excretion of Ca into
urine.
5) CT, therefore, has a DECREASING INFLUENCE ON BLOOD CALCIUM.
31. EXCRETION OF CALCIUM
1) Calcium is excreted partly through the kidneys and mostly
through the intestine.
2) The renal threshold for serum Ca is 10mg/dl.
STOOLS
Unabsorbed
calcium in the
diet
60-70%
URINE
50-
200mg/day
SWEAT
15mg/dy
32. CALCIUM IN THE TEETH
The teeth calcium is not subjected to regulation as observed for
bone calcium.
Thus the adult teeth, once formed, do not undergo decalcification
to meet the body needs of calcium.
However, proper calcium of teeth is important in the growing
children.
33. SYMPTOMS OF CALCIUM IMBALANCE
HYPERCALCEMIA
Hyperparathyroidism
Metastatic disease of bone
Vitamin A/D excess
Milk-alkali syndrome
Sarcoidosis
Immobilization (in setting of posttrauma
or osteoporosis)
Hyperthyroidism
HYPOCALCEMIA
Renal Failure
Hypoparathyroidism
Vitamin D deficiency
Tetany
35. HYPERCALCEMIA
The serum Ca level (normal 9-11 mg/dl) is elevated in hypercalcemia.
Hypercalcemia is associated with HYPERPARATHYROIDISM caused by increased activity of
parathroid glands.
The symptoms of hypercalcemia include lethary, muscle weakness, loss of appetite, constipation,
nausea, increased myocardial contractility and susceptibility to fractures.
36. HYPERPARATHYROIDISM
Hyperparathyroidism is characterized by hypersecretion of PTH. HPT occurs in three categories:
Etiology
1) Primary
Usually caused by a tumor (adenoma in 85% of all cases) or hyperplasia of the gland that produces an
increase in PTH secretion resulting in hypercalcemia and hypophosphatemia.
2) Secondary
When the parathyroid glands are stimulated to produce increased amounts of hormones to correct
abnormally low serum calcium levels in different physiologic or pathologic conditions like renal failure,
intestinal malabsorption syndrome, decrease of Vitamin D production, thus resulting in parathyroid
hyperplasia.
3) Tertiary
When long-standing secondary hyperplasia becomes autonomous in spite of correction of the underlying
stimulant (renal transplant).
37. ORAL MANIFESTATIONS OF HYPERPARATHYROIDISM
Dental abnormalities
Obliteration of pulp chamber by pulp stone
Alteration in dental eruption
Loosening and drifting of teeth
Malocclusions
Spacing of teeth
Partial loss of lamina dura
Periodontal ligament widening
Teeth become sensitive to percussion and mastication.
Floating teeth.
38. ORAL MANIFESTATIONS OF HYPERPARATHYROIDISM
Brown tumor
Generalized bone rarification of jaw
Soft tissue calcification
Hypercalcemia may results in sialolithiasis
Mandibular tori
Complaint of vague jaw bone pain.
39. ORAL MANIFESTATIONS OF HYPERPARATHYROIDISM
PALATAL ENLARGMENT IS CHARACTERISTIC OF RENAL OSTEODYSTROPHY ASSOCIATED
WITH SECONDARY HYPERPARATHYROIDISM
40. ORAL MANIFESTATIONS OF HYPERPARATHYROIDISM
THE PERIAPICAL RADIOGRAPH
REVEALS THE ‘GROUND GLASS’
APPEARANCE OF THE TRABECULAAE
AND LOSS OF LAMINA DURA IN A
PATIENT WITH SECONDARY
HYPERPARATHYROIDISM.
THE OCCLUSAL RADIOGRAPH OF THE
EDENTULOUS MAXILLARY ANTERIOR REGION
SHOWS A MULTILOCULAR RADIOLUCENCY
CHARACTERISTIC OF BROWN TUMOUR OF
PRIMARY HYPERPARATHROIDISM.
41. HYPOCALCEMIA
A DECREASE IN TOTAL PLASMA CALCIUM CONCENTRATION
BELOW 8.8mg/dl IN THE OF NORMAL PROTIEN CONCENTRATION.
42. HYPOPARATHYROIDISM
Hypoparathyroidism is a metabolic disorder characterized by low serum calcium and high serum
phosphorus concentrations due to a deficiency or absence of PTH secretion.
SIGNS AND SYMPTOMS
1) Hypoparathyroidism can cause hypocalcemia with consequent circumoral numbness, paresthesias of
distal extremities (finger and toes), muscle pain, abdominal pain or muscle cramping which can progress to
spasm or tetany. Laryngospasm or bronchospasm and seizures may also occur.
43. HYPOPARATHYROIDISM
Increased neuromuscular irritability (due to hypocalcemia) may be demonstrated by eliciting a Chvostek or
Trousseau sign. In positive Chvostek’s sign tapping, the facial nerve at its point of origin (anterior to ear
tragus) will cause spasm of facial musculature particularly of the lip and the alae of the nose. In Tousseau’s
sign Carpal, spasm occurs after inflation of the blood pressure cuff.
44. ORAL MANIFESTATIONS
1) The two most frequent dental abnormalities are enamel hypoplasia (enamel is thin), delayed eruption, and
there may be multiple unerupted teeth.
2) Teeth appear dull white in color with hypoplastic pitting. Crowns are small (microdontia) and the roots are
often short with blunt ends. In some teeth, roots are malformed, resulting from nontreated hypocalcemia
during the developmental phase of the dentition. A delay or cessation of dental growth and development, a
full complement of teeth is not always developed, premolars being the teeth most usually missing
(hypodontia). The teeth may show ankylosis, the jaws are generally short and wide with high arch palate.
Severe dental caries is usually noted in the deciduous and permanent teeth, the teeth are lost early due to
caries.
3) There may be chronic candidiasis of the oral mucosa and nail, paresthesia of the tongue or lips, and facial
twitching can occur.
45. CAUSES OF HYPOCALCEMIA
VITAMIN D DEFICIENCY
It is an important cause of hypocalcemia.
Vitamin D deficiency may result from inadequate dietary intake or decreased absorption due to
hepatobiliary disease or intestinalmalabsorption.
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.
46. RICKETS
RICKETS
1) Rickets in children is characterised by bone deformities due to incomplete
mineralization, resulting in soft and pliable bones and delay in teeth formation
49. HYPOPHOSPHATEMIC RICKETS
HYPOPHOSPHATEMIC rickets mainly results from defective renal
tubular reabsorption of phosphate. Supplementation of vitaminD long
with phosphate is found to be useful.
50. VITAMIN D RESISTANCE RICKETS
VITAMIN D RESISTANT RICKETS
1) Vitamin D-resistant rickets (VDRR), also known as hereditary or familial hypophosphatemia, is
characterized by a metabolic disturbance which causes defective calcification of mineralized structures.
2) VDRR is well established genetically as an X-linked dominant metabolic disorder, that may be
characterized by persistent hypophosphatemia and hyperphosphaturea associated with decreased renal
tubular reabsorption of inorganic phosphates.
51. VITAMIN D RESISTANCE RICKETS
RADIOGRAPHIC FEATURES
Dental radiographs reveal hypocalcification of teeth and the presence of large pulp chambers and alveolar
bone loss.
52. DENTAL FINDINGS
Dental findings that are often characteristic include dentin defects, unusually
large pulp chambers and enlarged pulp horns, in some cases the enamel is
hypoplastic.
These dental problems are more commonly associated with the primary than the
permanent dentition.
The most common intraoral radiologic findings include large pulp chambers,
short roots, poorly defined lamina dura and hypoplastic alveolar ridge.
53. RENAL RICKETS
In kidney diseases, even if vitamin D is available, Calcitriol is not synthesized.
Theses cases will respond to administration of calcitriol.
54. OSTEOMALACIA
The term is derived from greek ‘OSTEON’ = BONE AND ‘MALAKIA’= SOFTNESS.
The bones are softened due to insufficient mineralization and increases osteoporosis.
Patient are more prone to get fractures.
The abnormalities in BIOCHEMICAL PARAMETERS are slightly LOWER SERUM CALCIUM AND A
LOW SERUM PHOSPHATE.
Serum ALKALINE PHOSPHATASE, bone isoenzyme, is markedly increased.
55. OSTEOMALACIA
In osteomalacia (adult rickets) demineralization of bones occurs (bones become softer), increasing their
susceptibility to fractures.
Common cause is vitamin D deficiency.
56. OSTEOMALACIA
CLINICAL FEATURES
Pain and Chronic fatigue, starting insidiously.
Proximal muscles weakness.
Waddling gait.
Deformed pelvis and exaggerated lordosis.
Bowing of Lower limbs
57. OSTEOPOROSIS
Osteoporosis is characterized by demineralization of bone
resulting in progressive loss of bone mass.
OCCURRENCE
The elderly people(over 60 yr.) of both sexes are at risk for
osteoporosis.
It is more predominantly occurs in the postmenopausal women.
Osteoporosis results in frequent bone fractures which are a
major cause of disability among elderly.
58. OSTEOPOROSIS
ETIOLOGY
Etiology of osteoporosis is largely unknown, but it is believed
that several causitive factors may contribute to it.
The ability of calcitriol from vitamin D is decresaed with age,
particulary in he postmenopausal women.
Deficiency of sex hormones (in women) has been implicated in
the development of osteoporosis.
59. OSTEOPOROSIS
TREATMENT
Estrogen administration along with calcium supplementation(in combination with
vitamin D) TO POSTMENOPAUSAL WOMEN REDUCES THE RISK OF
FRACTURES .
Higher dietary intake of Ca (about) 1.5g/dy) is recommended for elderly people.
60. COMPARISON OF CALCIUM, PHOSPHORUS AND ALKALINE
PHOSPHATASE VALUES IN THE MORE COMMON DISORDERS OF BONE
AND CALCIUM METABOLISM
SERUM CALCIUM SERUM PHOSPHORUS SERUM ALKALINE
PHOSPHATASE
1) NORMAL 8.8B to 10.5 mg
ca/dl blood
2 to 5 mg p/dl
blood
1 to 4 units /dl
bood in adult
2)RICKETS Usually normal except in
tetany
Decreased Increased 20 to 40
x normal
3) OSTEOMALACIA Decreased Little if any change
4) PAGETS DISEASES Usually normal Usually normal elevated
5) HYPER
PARATHYROIDISM
Marked increase usually
decreased
Increaed 2 to 50
x normal
6) OSTEOGENESIS
IMPERFECTA
usually normal usually normal usually normal –at
times increased
7) SOLITARY BONE CYST Normal Normal Normal
8) TETANY 7mg ca /dl blood or
less
Normal or elevated Normal