7. The rigidity of skeleton which provides support and protection
for soft tissues, muscle contraction , the hardness and fitness
of the teeth, the stability of the cell membranes, as activator
of many hormones and last but not the least the heart beat it
self, is dependent on CALCIUM. With its myriads of functions
and complex mechanisms of control, calcium in both ionized and
unionized form is arguably one of the most important body
components.
INTRODUCTION
10. TOTAL BODY CALCIUM 1100-1200gms(1.5 % of body weight)
99% in the skeleton
4-5gms in soft tissue
1gm in ECF
NORMAL SERUM CALCIUM 8.8-10.4mg%
PLASMA CALCIUM occurs in 2 forms
Diffusible : 5.36mg% or 54-55%
oIonized 47%
oNon-ionized 5%
Non diffusible : 4.64mg% or 45-46%
MOST ABUNDANT MINERAL OF OUR BODY
11. ESTIMATION OF CALCIUM CONCENTRATION
• Ionized Ca concentration can be estimated from routine
laboratory tests, usually with reasonable accuracy
eg: plasma Ca is often low - Hypoalbuminemia
plasma Ca increases - Multiple myeloma
• Measured total plasma Ca decreases or increases by about 0.8
mg/dL (0.20 mmol/L) for every 1-g/dL decrease or increase in
albumin
12.
13. 8-ounce glass of milk = 300mg of calcium
2 ounces of Swiss cheese = 530mg of calcium
6 ounces of yogurt = 300 mg of calcium
2 ounces of sardines with bones = 240mg of calcium
6 ounces of cooked turnip greens = 220mg of calcium
3 ounces of almonds = 210mg of calcium
“Avoid foods causing calcium loss.. For example excess salt
and caffeine”
14. ADULT MALES AND FEMALES ….800mg
WOMEN DURING PREGNANCY
AND LACTATION ….1200mg
INFANTS UNDER 1 YEAR ….360-540mg
CHILDREN(1-18 YEARS) ….800-1200mg
DAILY REQUIREMENTS OF CALCIUM
.
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)
19. -Before the fifth month of
IUL very little calcium is
found in the fetus because
bone formation is only
starting.
-60% of the total deposition
occurs in the last trimester
which is the period of rapid
and extensive ossification
20. -One year old baby contains about 100 g of calcium, a gain of
70 g over the total calcium content at birth.
-The adult human weighing 70 kg contains about 1.2 to 1.4 kg
of calcium that is 1.5% of the body weight, 99% of which is
present in bones and teeth.
Mature fetus contains about 30 g of calcium which constitutes
about 3 to 4% of maternal calcium
Much greater drainage occurs after birth during lactation
21. TYPES OF CALCIUM
Calcium in plasma
3 forms:
Ionized (50%)
Nonionozed (8-10%)
Calcium bound to plasma protein (40-42%)
Calcium in bones:
2 forms:
Rapidly exchangeable calcium
Slowly exchangeable calcium
22. ABSORPTION & EXCRETION OF CALCIUM IN BODY
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
24. 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
25. EXCRETION
• 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 Ca in sweat is about 15mg.
26.
27.
28.
29. FACTORS CONTROLLING EXCRETION
• Calcium concentration in the body
• PTH (loop of henle and distal tubules)
• Plasma concentration of phosphate
↓CALCIUM EXCRETION
↑ PTH
↓ Extracellular fluid volume
↓ Blood pressure
↑ Plasma phosphate
↑CALCIUM EXCRETION
↓ PTH
↑ Extracellular fluid volume
↑ Blood pressure
↓ Plasma phosphate
30. HORMONES INFLUENCING CALCIUM ABSORPTION
• 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)
• GLUCOCORTICOIDS
31. FUNCTIONS OF CALCIUM
• 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
32.
33. Constituent of bone and teeth
• 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 platelet shaped crystals of
calcium hydroxyapatites. These give the hardness, strength
and concrete like elastic modulus to these tissues
34. Physiology of bone
• Bone is composed of tough organic matrix that is greatly
strengthened by deposits of calcium salts
• Average compact bone contains by weight about 30% matrix
and 70% salts
• Organic matrix of bone:
35. BONE SALTS
The crystalline salts deposited in the organic matrix of bone are
composed principally of calcium and phosphate.
The major crystalline salt is known as hydroxyapatite
[Ca10(PO4)6(OH)2].
36. Bone is constantly being reabsorbed and reformed,
under the cellular control….
Osteoblasts
Osteocytes
Osteoclasts.
38. Excitation-contraction coupling of all types
of muscles
THE ATTACHMENT OF CALCIUM TO TROPONIN
AND MOVEMENT OF TROPONIN-TROPOMYSIN
COMPLEX RESULTING IN EXPOSURE OF
BINDING SITES ON ACTIN MYOSIN
CROSS BRIDGING CAUSING A POWER
STROKE
41. Membrane permeability
• Ca2+ reduces membrane permeability to ions and water,
probably by binding with calmodulin of cell membranes and
consequently changing the conformation and hydration of
membrane proteins.
52. PARATHORMONE
-it provides a powerful mechanism for controlling extracellular calcium
and phosphate concentrations
Secreted by Chief cells of parathyroid gland
53. 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
54. ↓ BONE RESORPTION
↑ URINARY LOSS
↓ 1,25,(OH)2 D
PRODUCTION
↓
NORMAL BLOOD CALCIUM
↑
↑ BONE RESORPTION
↓ URINARY LOSS
↑ 1,25,(OH)2 D
PRODUCTION
SUPPRESS PTH
RISING BLOOD CALCIUM
FALLING BLOOD CALCIUM
STIMULATE PTH
55. ON BONE:
- RAPID PHASE
- SLOW PHASE
ON KIDNEYS:
ON GASTROINTESTINAL
TRACT
56. Role of PTH in the activation of VITAMIN D
VITAMIN D IS A HORMONE BY CLASSIC CRITERIA: MADE
IN ONE PLACE (OR SEQUENTIALLY SEVERAL PLACES!),
AND ACTING IN OTHER
DAILY DIETARY ALLOWANCE RECOMMENDED:
- From infancy till puberty is 10 mcg of cholecalciferol (400
IU of vitamin D)
- In young adulthood, its 7.5 mcg
- After 25 yrs, 5 mcg required
Pregnancy and lactation 10 mcg
59. 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
60. 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.
61. Role of Ca ion in regulating 1,25 Dihydroxycholecalciferol
ca ion 25 Dihydroxycholecalciferol
ca ion - PTH secretion
62. Regulation of PTH secretion:
Blood level of calcium:
-inversely proportional
conditions when PTH secretion decreases
Blood level of phosphate:
- directly proportional
63. CALCITONIN
• 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
64. ACTIONS
ON BLOOD CALCIUM LEVEL-
It reduces the blood calcium concentration
ON BONE
Stimulates osteoblastic activity
Inhibits osteoclastic activity
Increases excretion of Ca through urine
Inhibits reabsorption of Ca from renal tubules
ON GIT
Inhibits intestinal absorption of
Ca++and PO4
---
ON KIDNEYS
65. ON BLOOD PHOSPHATE LEVEL-
On bones:
Inhibits resorption of phosphate from bone
On kidneys:
Increases excretion of phosphate through urine
66. 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
67. Applied physiology –
Disorders of parathyroid glands ( two types )
1. HYPOPARATHYROIDISM
-causes: Parathyroidectomy
Thyroidectomy
Deficiency of receptor for PTH
1. HYPERPARATHYROIDISM
Primary hyperparathyroidism
Secondary hyperparathyroidism
Tertiary hyperparathyroidism
68. 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 sign
69. 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
70. CALCIUM AND DENTAL CARIES
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
71. CALCIUM AND SALIVA
• Calcium content of submandibular saliva is almost double the
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
73. • 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 3quater present in bones and teeth in form of apatite
crystal
74. 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%
76. Adequate Intake
•0-6 months 100 mg/day
•6-12 months 275 mg/day
Estimated Average Requirements
•1-3 years 380 mg/day
•4-8 years 405 mg/day
•9-18 years 1,055 mg/day
•19-70+ years 580 mg/day
•Pregnant & Same as for nonpregnant &
lactating women nonlactating women
Reference : Dietary Reference Intakes, Food and Nutrition
Board, National Academy of Sciences-Institute of Medicine, 1997
77. Total phosphate:500-800
mg
Bones and teeth
80-85%
Inorganic
(0.5-
1mg/dl)
(Adults:3-
4mg/dl)
(children:5-6mg/dl)
Normal plasma levels:
2.5-4.5 mg/dl
Organic
78. Mechanism– co-transport Na
P is absorbed in duodenum and
other parts of small intestine by
active transport and passive
diffusion.
79. Approximately 3mg/kg/day of Phosphorous enters the bone
.
In plasma is filtered in glomeruli of which 85-95% gets
reabsorbed actively in PCT. Its excretion in urine is:
INCREASED BY:
Vitamin D excess;
hyperparathyroidism;
high phosphate diet.
DECREASED BY:
GH, during lactation;
hypoparathyroidism;
low phosphate diet.
80. EXCRETION OF PHOSPHOROUS
• It is excreted in urine and feaces
• Urine phosphate constitutes about 60% of total excretion and
rest is excreted in feaces.
Infant 240 - 400mg
Children 800 - 1200mg/day
Adults 800mg/day
Pregnancy & Lactation 1200mg/day
81. IN BONE
STRUCTURAL COMPONENT
INTERMEDIATE METABOLISM
GENETIC MATERIAL
FUNCTIONS OF PHOSPHOROUS
82. Important Functions to note
are………..
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.
88. Etiologies of Hypophosphatemia
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
89. 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
Etiologies of Hypophosphatemia
97. OSTEOMALACIA OR ADULT
RICKETS
• 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.
98.
99.
100. PSEUDOHYPOPARATHYROIDISM
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
101. Symptoms begin in children of about 8 years
Tetany and seizures
Hypoplasia of dentin or enamel and delay or absence of
eruption occurs in 50% of people with the disorder
Rx: Vitamin D and calcium
Adequate amount of phosphorous in diet
106. PRIMARY HYPERPARATHYROIDISM
• 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
– FAMILIAL HYPERPARATHYROIDISM: 1o HPT WITHOUT
THE OTHER TUMORS SEEN IN MEN-1 OR MEN-2a
– FAMILIAL BENIGN HYPOCALCIURIC HYPERCALCEMIA
107. Characterized by:
• ↑ serum Ca2+
• ↓ serum phosphate
• ↑ urinary phosphate excretion (phosphaturic effect of PTH)
• ↓ 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
108. Clinical features
“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, Peptic Ulcrs
• CNS Alterations Including Depression, Lethargy And Seizures
• Neuromuscular Abnormality Including Weakness And Hypotonia
109. • Metastatic calcifications seen in subcutaneous soft tissues,
sclera, dura and region around joints
• Brown tumor
• Affect mandible, clavicles, ribs and pelvis
• Osteitis fibrosa cystica- develops from central degeneration
and fibrosis of long standing brown tumor
114. Radiological features
• 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
115. Granular appearance of skull
in patient having renal
osteodystrophy
Solitary “punched out”
radiolucency in calvarium
represents a Brown tumour in
secondary
hyperparathyroidism
122. SECONDARY HYPERPARATHYROIDISM
• 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
123. • In patients with secondary hyperparathyroidism caused by
end stage renal disease, striking enlargement of jaw occurs
Palatal enlargement is a characteristic of renal
osteodystrophy associated with secondary
hyperparathyroidism
124. • Bone lesions in digits, clavicle
• Mottling of skull, erosion of the distal clavicle, rib fractures
and necrosis of femoral head.
• Children show osteomalacia
125. Treatment
• 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
126. 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