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Calcium metabolism
1. CALCIUM METABOLISM
Dept Of Oral And Maxillofacial Surgery ,VSPM’S Dental College, Nagpur
Presented by: Guided by:
Dr. Sapna K Vadera Dr. S.R.Shenoi
(P.G. Student) (Prof, Guide and H.O.D)
2. CONTENTS
Introduction
History
Distribution
Daily requirements
Dietary sources
Functions
Factors controlling absorption
Hormonal control
Other hormones affecting metabolism
Clinical importance
Conclusion
3. INTRODUCTION
• METABOLISM
It is defined as the chemical and physical process in an organism
by which protoplasm is produced , sustained , and then
decomposed to make energy available.
It is the biochemical modification of chemical compounds in
living organisms and cells that includes the biosynthesis of
complex organic molecules (anabolism) and their breakdown
(catabolism).
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
4. • MINERALS
The minerals in foods do not contribute directly to energy needs
but are important as body regulators and as essential constituents
in many vital substances within the body.
Inorganic elements and only variation is in ionic state.
Retain their chemical identity.
They are almost indestructible.
Minerals are water soluble:
- Influence water and acid-base balance in the body.
INTRODUCTION
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
5. Principal Minerals include - Calcium, Phosphorous,
Magnesium, Sodium, Potassium and Sulphur.
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.
INTRODUCTION
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
6. CALCIUM HISTORY
• Latin- calx or calcis meaning ”lime”
• Known as early as first century when ancient Romans prepared lime
as calcium oxide.
• Isolated in 1808 by Englishman Sir Humphrey Davy through the
electrolysis of a mixture of lime (CaO) and mercuric oxide (HgO).
• In 1883 Sir Sydney Ringer demonstrated the biological significance of
calcium.
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
7. CALCIUM
• Soft grey alkaline earth metal
• Symbol ‘Ca’
• Atomic Number 20
• Atomic weight 40 g/mol
• Single oxidation state +2
• Fifth most abundant element
in Earth´s crust
• Essential for living organisms
Harrison MR, Edwards PP, Klinowski J, Thomas JM, Johnson DC, Page CJ. Ionic and metallic clusters of the alkali metals in
zeolite Y. Journal of Solid State Chemistry. 1984 Oct 31;54(3):330-41.
8. CALCIUM OCCURRENCE
In nature
• Does not exist freely
• Occurs mostly in soil systems as limestone (CaCO3), gypsum
(CaSO4*2H2O) & fluorite (CaF2)
In the body
• The most abundant mineral
• Average adult body contains approx 1 kg
Dorozhkin SV. Calcium Orthophosphates: Occurrence, Properties and Major Applications. Bioceramics Development and
Applications. 2014 Nov 19;2014.
9. Dorozhkin SV. Calcium Orthophosphates: Occurrence, Properties and Major Applications. Bioceramics Development and
Applications. 2014 Nov 19;2014.
DISTRIBUTION
10. DISTRIBUTION
• 2% of body weight
99% in bones
1% in body fluids
• Plasma (Extracellular fluid)
– 2.25 – 2.75 mmol/l
• Cell (Intracellular fluid)
– 10 mmol/l
Dorozhkin SV. Calcium Orthophosphates: Occurrence, Properties and Major Applications. Bioceramics Development and
Applications. 2014 Nov 19;2014.
11. PLASMA CALCIUM
Diffusible
• 50% Ca2+ ionized
• 10% combined with anions (citrate, phosphate) –
non-dissociated
Nondiffusible
• 40% combined with plasma proteins
Reid IR, Bristow SM, Bolland MJ. Calcium supplements: benefits and risks. Journal of internal medicine. 2015 Oct
1;278(4):354-68.
12. Reid IR, Bristow SM, Bolland MJ. Calcium supplements: benefits and risks. Journal of internal medicine. 2015 Oct
1;278(4):354-68.
50%
40%
10%
Percentage of Calcium
Free or ionized calcium
Protein bound(mainly albumin) 40
complex with anions-
citrates,bicarbonates,lactates,phos
phates
13. 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.
The serum level of calcium is closely regulated with normal total
calcium of 9-10.5 mg/dL and normal ionized calcium of 4.5-5.6 mg/dL.
Serum Phosphate levels
• Children - 4 to 7 mg/dL
• Adults - 3 to 4.5 mg/dL
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
14. RECOMMENDED CALCIUM INTAKE
Age Amount of calcium
Infants
Birth to six months 400mg
6 months to 1 year 600mg
Children / young adults
1 – 10 years 800 – 1200mg
11 – 24 years 1200 – 1500mg
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
15. Adult women
Pregnant and lactating 1200 – 1500mg
Over 65 yrs old 1500mg
Adult men
25 – 64 yrs old 1000mg
Over 65 yrs old 1500mg
RECOMMENDED CALCIUM INTAKE
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
19. FUNCTIONS OF PHOSPHATE
Formation of bones.
Like calcium, important component of teeth.
Important constituent of cells.
Forms energy rich bonds in ATP.
Forms co-enzymes.
Regulates blood and urinary pH.
Forms organic molecules like DNA & RNA.
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
23. ABSORPTION OF CALCIUM
Calcium is taken through dietary sources as calcium
phosphate, carbonate, tartrate and oxalate.
It is absorbed from the gastrointestinal tract in to
blood and distributed to various parts of the body.
Two mechanisms have been proposed for the absorption of
calcium by gut mucosa:
Simple Diffusion.
An active transport process, involving energy
and calcium pump.
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
24. 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.
In the bone, the calcium may be deposited
or resorbed depending upon the level of
calcium in the plasma.
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
25.
26. 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.
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
27. Factors acting on the mucosal cells
Vitamin D
Pregnancy and growth
PTH
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
28. VITAMIN-D
CALCITRIOL (1,25-DHCC)
It is the biologically active form of Vit-D.
It regulates plasma levels of Ca and P.
Calcitriol acts at 3 different levels intestine, kidney, bones
Action on Intestine
• It increases the intestinal absorption of Ca & P in the intestinal cells
calcitriol binds with a cytosolic receptor to form a calcitriol-receptor
complex
• This complex then approaches the nucleus and interacts with a specific
DNA leading to synthesis of Ca binding protein
• This protein increases the Ca uptake by intestine
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
29. 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
VITAMIN-D
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
30. PREGNANCY AND
GROWTH
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.
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
31. 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.
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
32. 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
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
33. 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
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
34. Amount of dietary calcium and phosphates
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
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
35. Phytic acid and phytates
They are 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
Fats
They combines with calcium and form insoluble calcium , thus
decreasing calcium absorption.
Oxalates
They are present in spinach and green leafy vegetables. They form
oxalate precipitates with calcium present in the diet thus decreasing
their availability.
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
36. Bile salts
They increases calcium absorption by promoting metabolism of
lipids.
Protein and amino acids
High protein diet increases calcium absorption as protein forms
soluble complexes with calcium and keeps calcium in a form that is
easily absorbable.
Carbohydrates
• Certain carbohydrates like lactose promotes calcium
absorption by creating the acidity in the gut as they favors the
growth of acid producing bacteria.
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
37. 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.
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
38. HORMONAL CONTROL OF CALCIUM
& PHOSPHATE METABOLISM
• Three hormones regulate calcium and phosphate metabolism.
Vitamin D
PTH
Calcitonin
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
39. 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.
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
40. DAILY REQUIREMENT
• Adults – 2.5mg
• Lactating mother
Pregnancy
Adolescents
Infants
5mg
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
41. DIETARY SOURCE
Cod liver oil
Fish- Salmon
Egg, liver
ACTIONS
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.
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
42.
43. 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.
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
44. Histologically – two types of cells
• Chief cells (forming PTH)
• Oxyphilic cells (replaces the chief cells stores hormone)
PARATHYROID HORMONE
(PTH)
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
45. PARATHYROID HORMONE
Single chain polypeptide
Consist of 84 amino acids
Plasma half life – 20-30 minutes
Plasma concentration – 10-50ug/ml
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
46.
47. 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 re absorption in the
proximal tubule and therefore increases phosphate excretion
Parathormone increases renal Calcium re absorption in the distal
tubule, which also increases the serum calcium.
Net effect of PTH ↑ serum calcium
↓ serum phosphate
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
48. 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
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
49. 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
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
50. ACTION OF CALCITONIN
Net EFFECT of calcitonin decreases Serum Ca
Target site
-Bone (osteoclasts)
- decreased ability of osteoclasts to resorb bone
OSTEOCLASTS CELLS
◦ Lose their ruffled borders
◦ Undergo cytoskeletal
rearrangement
◦ Decreased mobility
◦ Detach from bone
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
51. • 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
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
52.
53. EFFECTS OF OTHER HORMONES ON
CALCIUM METABOLISM
GROWTH HORMONE
INSULIN
TESTOSTERONE & OTHER HORMONES
LACTOGEN & PROLACTIN
STEROIDS
THYROID HORMONES
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
54. 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
Stimulates stomatomedian C which acts on cartilage to increase the length of
bones
GROWTH HORMONE
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
55. 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
EFFECTS OF OTHER HORMONES ON
CALCIUM METABOLISM
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
56. THYROID HORMONE
In infants stimulation of bone growth
In adults increased bone metabolism
increased calcium mobilization
EFFECTS OF OTHER HORMONES ON
CALCIUM METABOLISM
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
57. 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.
EFFECTS OF OTHER HORMONES ON
CALCIUM METABOLISM
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
58. 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.
Stools
Unabsorbed
calcium in
the diet
60 – 70%
Urine
50-
200mg/day
Sweat
15mg/day
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
59. Daily turnover rates of Ca in an adult
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
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
60. 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.
Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in companion animal medicine. 2012
Nov 30;27(4):159-64.
61. INCREASED SERUM CA:
Hyperparathyroidism.
Hypervitaminosis (Vit. D).
Multiple myeloma.
Sarcoidosis.
Thyrotoxicosis.
Milk alkali syndrome.
Infantile hypercalcemia
DECREASED SERUM CA:
Renal failure.
Hypoparathyroidism.
Vit. D deficiency.
Tetany.
Malabsorption syndrome.
SYMPTOMS OF CALCIUM -
PHOSPHORUS IMBALANCE
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
62. 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.
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
63. CLASSIFICATION
PTH absent
Hereditary hypoparathyroidism
Acquired hypoparathyroidism
PTH ineffective
Chronic renal failure
Lack of Vit D
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
64. Results from a deficiency in or absence of PTH.
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.
HYPOPARATHYOIDISM
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
65. CAUSES
Accidental removal of gland during surgery
occasionally from autoimmune destruction of the gland.
Congenital absence of the gland
Atrophy of the gland-Idiopathetic
Pseudohypoparathyroidism
CLINICAL SIGNS &
SYMPTOMS
Hyperactive reflexive
Spontaneous
muscular
contractions
Convulsions
Laryngeal spasm
CLINICAL FEATURES ARE
DEVELOPMENTAL ANOMALIES
INCLUDES
short stature
Short metacarpal or
metatarsal bones
Mental retardation
66. ORAL MANIFESTATIONS:
Enamel hypoplasia and
dental dysplasia
Dryness of the mucous membranes
Angular cheilitis
Circumoral parasthesia
Disturbances in tooth eruption
Root defects
Hypodontia and impacted teeth
Large pulp chambers were observed in the deciduous teeth and
the permanent teeth,
Thickening of the lamina dura was observed in the permanent
teeth.
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
67. •Enamel hypoplasia
•External root resorption
•Delayed eruption
•Root dilaceration
Radiographic features
Ash, Major M., Jr. and Nelson, S.J (2003). Dental anatomy, physiology, and occlusion (8th ed.). Philadelphia:
W.B. Saunders. ISBN 0-7216-9382-2.
68. PSEUDOHYPOPARATHYROIDISM
It is the result of defective G protein in kidney and bone,
which causes end-organ resistance to PTH.
There is hypocalcemia and hyperphosphatemia that is not
correctable by administration of exogenous PTH.
Circulating endogenous PTH levels are elevated.
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
69. MANAGEMENT
Administration of extremely large quantities of
vitamin D, to as high as 100,000 units per day,
along with intake of 1 to 2 grams of calcium, keeps
the calcium ion concentration in a normal range.
HYPOPARATHYOIDISM
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
70. 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 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
CAUSES OF HYPOCALCEMIA
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
71. Occurs in children between 6 months to 2 years of age.
Affects long bones
Lack of calcium causes failure of mineralization resulting
into formation of cartilagenous form of bone.
Most critical area that gets affected is the center
endochondral ossification at the epiphyseal plates.
RICKETS
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
72. RICKETS
CLINICAL
FEATURES
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
73. Developmental abnormalities of
dentin and enamel
Delayed eruption
Misalignment of teeth in the jaw
High caries index
Enamel hypoplasia
RICKETS
ORAL
MANIFESTATIONS
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
74. Nutritional Rickets
Vitamin D Resistant Rickets.
Vitamin Dependent Rickets.
Oncogenous Rickets.
TYPES OF RICKETS
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
75. Primarily, Vitamin D deficiency due to poor dietary intake
- Vegetarian diet(cereals, vegetables, fruits).
- Non-vit.D supplimented formulations for children.
Children with chronic diarrhea or malabsorption disorders e.g
cystic fibrosis.
Exclusive breastfed infants in mothers with poor uv light
exposure or mother with vit D deficiency
Dark skin infants at higher risk.
Premature infants on parenteral nutrition.
NUTRITIONAL RICKETS
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
77. Also referred as X-linked hypophosphatemia.
Non-nutritional rickets.
Some mothers of affected siblings manifest the disease features.
Autosomal dominant and sporadic case may occur.
Renal tubular disorder leading to excessive loss of phosphorus
VITAMIN D RESISTANT RICKETS
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
78. No profound myopathy, rachitic rosary, tetany,or enamel
defects.
Radiographic findings :
- Metaphyseal widening and fraying.
- Cupping of metaphysis of proximal and distal tibia,
distal femur, radius and ulna
Manifestations:
VITAMIN D RESISTANT RICKETS
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
79. Radiographic features:
Dental radiographs reveal hypocalcification of teeth and the
presence of large pulp chambers and alveolar bone loss.
VITAMIN D RESISTANT RICKETS
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
80. VITAMIN D RESISTANT RICKETS
Oral manifestations:
Histological evidence of widespread formation of globular,
hypocalcified dentin, with clefts and tubular defects occuring in
the region of pulphorns.
Periapical involvement of grossly normal appearing deciduous and
permanent teeth, followed by the development of multiple
gingival fistulas.
Abnormal cementum and the alveolar bone pattern
Lamina dura is frequently absent or poorly defined.
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
81. Defect in the proximal tubular reabsorption of phosphate.
Defect in conversion of 25-(OH)D to 1,25D(OH) .
Reduced activity of Na+ dependent phosphate transport
resulting in excessive PO4 excretion.
Abnormal gene in this disorder is on X-chromosome
22p(PHEX) OR Phosphate regulating gene.
In autosomal dominant there’s mutation in Fibroblast Growth
Factor ,FGF23 which impairs PO4 reabsorption.
Pathogenesis:
VITAMIN D RESISTANT RICKETS
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
82. VITAMIN D DEPENDENT RICKETS
Also known as Pseudo vitamin D deficiency OR Hypocalcemic
Vitamin D resistant Rickets.
Two types exist;
Type 1.( VDDR1)
Type 2.(VDDR2)
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
83. Oncogenous Rickets
(Primary hypophosphatemic Rickets)
• Rickets due to a mesenchymal tumor .
• Mostly benign.
• Occur in sites difficult to detect.e.g nasal antrum, pharynx,
small bones of the hands,etc.
• May be associated with other syndromes like
Neurofibromatosis.
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
84. • They elaborate massive amounts of F6F23 gene,which impairs
hydroxylation of 25-(OH)D
• And impairing PO4 reabsorption.
• Remission occurs on tumor excision.
Oncogenous Rickets
(Primary hypophosphatemic Rickets)
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
85. Treatment:
Oral therapy:
Vitamin D- 0.5-1g/24 hr for children 2-4 yrs
1-4g/24 hr for children > 4 yrs.
For patients requiring parenteral administration of phosphate, an
initial phosphate dose of 0.08 mmol per kg body weight may be given
over six hours. The dose may be increased to 0.16 mmol per kg if a
patient has serious clinical manifestations.
With early diagnosis and compliance limb deformity Can be
minimized.
• Corrective osteotomy for deformed limbs should be delayed till
radiological healed rickets is noted and serum alkaline phosphatase
levels are normal.
RICKETS
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
86. OSTEOMALACIA
• Softening of bones due to defective mineralization (Ca and PO4).
• Also due to excessive resorption of bones in
hyperparathyroidism.
• Common cause is vit.D deficiency.
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
87. Main causes
Inadequate Ca absorption
Phosphate deficiency due to renal losses
OSTEOMALACIA
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
88. Other causes
• Renal tubular acidosis
• Malabsorption syndrome.
• Malnutrition during pregnancy.
• Hypophosphatemia.
• Tumor induced osteomalacia.
• Drugs-anticonvulsants, anti TB, Steroids, glucocorticoids
OSTEOMALACIA
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
89. Clinical features
Pain and Chronic fatigue, starting insidiously.
Proximal muscles weakness.
Waddling gait.
Deformed pelvis and exaggerated lordosis.
Bowing of Lower limbs
Biochemical features are similar to Rickets except in renal
osteodystrophy where serum phosphate is high.
OSTEOMALACIA
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
90. LAB DIFFERENCES
Disorder
Serum
Ca
Serum P Alk phos PTH
25-(OH)
vit D
1,25-(OH)
vit D
Urinary
Ca
Osteomalcia low low high high low low low
Osteoporosis normal normal variable normal normal normal normal
Tumor induced
osteomalacia
low very low low low low low low
Osteopetrosis normal normal high normal normal normal normal
91. Radiographic features
Pseudofractures-Common on
scapula, medial femoral cortex and
pubic rami.
Biconcave vertebral bodies.
Femoral neck fractures.
OSTEOMALACIA
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
92. IDIOPATHIC HYPOPARATHYROIDISM
It 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.
CAUSES OF HYPOCALCEMIA
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
93. 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
CAUSES OF HYPOCALCEMIA
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
94. HYPOPROTEINEMIA
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.
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
CAUSES OF HYPOCALCEMIA
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
95. SEPTIC SHOCK
May be associated with hypocalcemia due to suppression of PTH release
and conversion of 25(OH)D3 to 1,25(OH)2D3.
DRUGS
Associated with hypocalcemia include those generally used to treat
hypercalcemia anticonvulsants (phenytoin, phenobarbital) and rifampin,
which alter vitamin D metabolism.
CAUSES OF HYPOCALCEMIA
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
97. It 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).
TETANY
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
100. Emergency treatment: calcium gluconate inj 0.23
mmol Ca/ml
Dose : 10ml iv in first instance
Oral calcium tablets
- Calcium gluconate 54mg Ca/tab
- Calcium gluconate 90mg/tab
- Sandoz calcium 400mg /tab
- Sandoz calcium 135mg /tab
Long term treatment: vitamin D therapy
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
101. Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
102. HYPERCALCEMIA
Elevated serum calcium level up to 12- 15 mg/dl
Conditions leading to hypercalcemia
Hyperparathyroidism
Acute osteoporosis
Thyrotoxicosis
Vitamin D intoxication
DISORDERS OF CALCIUM
METABOLISM
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
104. 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
HYPERCALCEMIA
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
105. 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
HYPERCALCEMIA
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
106. 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
VITAMIN D INTOXICATION
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
107. 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
HYPERCALCEMIA
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
108. 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
HYPERCALCEMIA
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
109. HYPERPARATHYROIDISM
Primary hyperparathyroidism
Secondary hyperparathyroidism
Tertiary hyperparathyroidism
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
110. PRIMARY HYPERPARATHYROIDISM
Tumor of one of PTH gland.-single adenoma
Adenomas are located at inferior portion of parathyroid gland
Mostly seen in women than men & children
Extreme osteoclastic activity in bones
Elevates Ca ion conc. in ECF which depresses phosphate ions.
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
111. 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
PRIMARY HYPERPARATHYROIDISM
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
112. Oral Manifestations:
Dehydration
Mandibular or maxillary tumors of the bone, which on biopsy
display a brown tumor of von Recklinghausen
Increased incidence of tori;
Reduction in cortical bone content leading to osteoporosis
PRIMARY HYPERPARATHYROIDISM
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
113. BROWN TUMOR
Hyperparathyroidism results in
disorders of bone and mineral
metabolism.
Diffuse and focal lesions may arise
in multiple bones.
On occasion, a patient
with undiagnosed hyper-
parathyroidism presents with a
lytic lesion that may be mistaken
for a tumor.
These lesions are termed
"Brown Tumors" due to the
presence of old hemorrhage in
the lesion.
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
114. According to Schour and Massler, malocclusion
caused by a sudden drifting with definite spacing of the teeth
may be one of the first signs of the disease.
Normal trabecular pattern is lost & replaced by granular or
ground glass appearance.
Moth-eaten like appearance of jaw bones
Teeth are mobile and migrate.
Lamina dura diminished or completely absent in 10% of cases.
PRIMARY HYPERPARATHYROIDISM
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
115. PRIMARY HYPERPARATHYROIDISM
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
116. Osteitis Fibrosa Cystica
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.
PRIMARY 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.
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
117. PRIMARY HYPERPARATHYROIDISM
Osteitis Fibrosa Cystica
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
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118. SECONDARY HYPERPARATHYROIDISM
Vitamin D deficiency
Chronic renal disease
Hypocalcemia, hyperphosphatemia & increased serum
alkaline phosphatase
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
119. TERTIARY HYPERPARATHYROIDISM
Parathyroid tumor develop from long standing secondary
hyperparathyroidism.
Serum calcium is increased
Phosphorus is normal to increased
Alkaline phosphatase is increased
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
120. TREATMENT OF HYPERCALCEAMIA
Emergency treatment:
The solution of IV infusion contains a mixture of mono and
dihydrogen phosphate so that pH is 7.4.
500ml of this solution should be infused over 4 to 6 hours.
Long term phosphate treatment:
Oral phosphate is given as diphosphate. Choice depends
upon serum phosphate levels.
Dose 100 to 300ml per day in divided doses
Phosphate sandoz tablet
Phosphorous :500mg
Na: 21 mmol
K : 3mmol
Dose: 1 to 6 tab daily
Emkey RD, Emkey GR. Calcium metabolism and correcting calcium deficiencies. Endocrinology and
metabolism clinics of North America. 2012 Sep 30;41(3):527-56.
121. CONCLUSION
Disturbances in calcium and phosphate intake,
excretion and trans cellular shift result in deranged
metabolism accounting for abnormal serum levels.
As a result of the essential role played by these minerals in
intra and extracellular metabolism, the clinical manifestations of
related disease states are extensive.
Thus, an understanding of the basic mechanism of calcium,
phosphate metabolism and pathophysiology of various related
disorders is helpful in guiding therapeutic decisions.
122. REFERENCES
• Cline J. Calcium and vitamin d metabolism, deficiency, and excess. Topics in
companion animal medicine. 2012 Nov 30;27(4):159-64.
• Harrison MR, Edwards PP, Klinowski J, Thomas JM, Johnson DC, Page CJ.
Ionic and metallic clusters of the alkali metals in zeolite Y. Journal of Solid
State Chemistry. 1984 Oct 31;54(3):330-41.
• Dorozhkin SV. Calcium Orthophosphates: Occurrence, Properties and Major
Applications. Bioceramics Development and Applications. 2014 Nov
19;2014.
• Reid IR, Bristow SM, Bolland MJ. Calcium supplements: benefits and risks.
Journal of internal medicine. 2015 Oct 1;278(4):354-68.
• Emkey RD, Emkey GR. Calcium metabolism and correcting calcium
deficiencies. Endocrinology and metabolism clinics of North America. 2012
Sep 30;41(3):527-56.