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Presented by :
Faisal Noor Ahmad
PG 1st year
CALCIUM
METABOLISM
Under the Guidance of :
Dr. Ravishankar T.L
Dr. Amit Tirth
Dr. Vaibhav Tandon
Dr. Smita Chandra
INTRODUCTION
Calcium is very essential for many activities in the body such as-
• Neuronal activity
• Skeletal muscle activity
• Cardiac activity
• Smooth muscle activity
• Secretory activity of glands
• Coagulation of blood
Normal Range : 9- 11 mg%
• Daily Requirement
• Adults : 500 mg/day
• Children: 1200 mg/day
• Pregnancy and Lactation: 1500 mg/day
• 99% of calcium is present in bone and rest in plasma.
Types of Calcium :
1. Calcium in plasma
2. Calcium in bone
1. Calcium in Plasma
Calcium is present in three forms in Plasma:
• Ionized or diffusible calcium
• Non ionized or non-diffusible calcium
• Calcium bound to albumin
IONISED CALCIUM
• Found freely in plasma
• Forms about 50% of plasma calcium
• Essential for vital functions like
a. Neuronal activity
b. Muscle contraction
c. Cardiac activity
d. Secretions in gland
e. Blood coagulations
Non Ionized Form
• 8-10% of plasma calcium
• For e.g. Calcium Bicarbonate
•CALCIUM BOUND TO ALBUMIN
• About 40-42% of calcium is bound with plasma protein
2. CALCIUM IN BONES
Calcium in bones is of two types-
• Small quantity of readily exchangeable activity
• Large quantity of stable calcium
The exchangeable calcium is the one that is removed from the bones.
Helps to maintain the plasma calcium level
The stable calcium is the one ,which is constantly removed and
deposited in the bones
Helps in bone remodeling
Schematic Diagram Showing Calcium Metabolism
Regulation of Blood Calcium Level
• Absorbed from GI tract into blood and distributed to various parts of
the body.
• Depending upon the blood level , the calcium is either deposited in
the bone or removed from the bone.
• All these processes are finely regulated mainly by three hormones
I. Parathormone
II. 1,25 dihydroxycholecalciferol
III. Calcitonin
I. PARATHORMONE
• Protein hormone
• Secreted by Parathyroid gland
• Increases the blood calcium level by mobilizing calcium from
bone(resorption)
II. 1,25 DIHYDROXYCHOLECALCIFEROL
• Steroid hormone
• Synthesized from vitamin D
• Increases blood calcium level by increasing the calcium absorption
from small intestine
III. CALCITONIN
• Calcitonin is secreted by parafollicular cells of thyroid gland.
• Thyroid gland is a calcium-lowering hormone.
• It reduces the blood calcium level mainly by decreasing bone
resorption.
 Action of Calcitonin-
On Bone
• Calcitonin facilitates deposition of calcium on bones(osteoblastic activity)
• Also suppresses the activity of osteoclasts which are responsible for
resorption of calcium from bones.
• Inhibits the development of new osteoclasts in bones
On Kidney
• Calcitonin increases the excretion of calcium through urine ,by inhibiting
the reabsorption of calcium from the renal tubules
On Intestine
• Prevents the absorption of calcium from intestine into blood
Schematic Diagram showing regulation of Blood Calcium Level
ACTIONS OF PARATHORMONE
• Maintains the blood calcium level by acting on
bones
kidneys and
GI tract
• Parathyroid hormone increases :
Resorption of calcium from the bones
Reabsorption of calcium from renal tubules
Absorption of calcium from GI tract
 On Bone
• PTH is responsible for the resorption of calcium from bones by
stimulating both osteoblasts and osteoclasts of the bone.
• Resorption of calcium from bone occurs in two phases :
a. Rapid phase
b. Slow phase
a) RAPID PHASE
Occurs within minutes after the release of PTH from parathyroid
glands.
After reaching the bone ,PTH gets attached with the receptors on the
cell membrane of osteoblasts and osteocytes.
• The hormone- receptor complex increases the permeability of the
membrane of these cells for calcium ions.
• Increases the calcium pump mechanism allowing calcium ions to
move from these cells into the plasma.
b) SLOW PHASE:
Slow phase of calcium resorption from bone is by activation of
osteoclasts.
When osteoclasts are activated by PTH ,some proteolytic enzymes are
released from the lysosomes of these cells.
Apart from the proteolytic enzymes ,several acids such as citric acid
and lactic acid are also released
• All these substances digest or dissolve the organic matrix of the bone,
releasing the calcium ions. calcium ions slowly move into the
plasma. Thus, PTH releases calcium from bones by activating
osteoclasts.
 On kidneys
• PTH increases the reabsorption of calcium from the renal tubule
along with magnesium ions and hydrogen ions.
• Calcium is reabsorbed from DCT and PCD.
• PTH also increases the formation of 1,25- dihydroxycholecalciferol
(activated form of vitamin D) which is also absorbed in the PCT.
ON GIT
• PTH increases the absorption of calcium ions from the GI tract
indirectly.
• Increases the formation of 1,25-dihydroxycholecalciferol in kidneys.
This vitamin in turn increases absorption of calcium ions from GIT.
Activation of vitamin D
• Important form of vitamin D is vitaminD3
• Also known as cholecalciferol
• Synthesized in skin from 7-dehydrocholestrol by the action of UV rays
from the sunlight.
• Also obtained from dietary sources
FIRST STEP
• Cholecalciferol is converted into 25-hydroxycholecalciferol in the liver.
• This process is limited and is inhibited by 25-hydroxycholecalciferol
itself by feedback mechanism.
 This inhibition is essential for two reasons:
-Regulation of the amount of active vitamin D
-Storage of vitamin D for months together
• If vitamin D3 is converted into 25 hydroxycholecalciferol
without getting properly inhibited , it will remain in the body
only for 2-5 days.
• But Vitamin D3 is stored in liver for several months.
SECOND STEP-
• 25-hydroxycholecalciferol is converted into 1,25-
dihydroxycholecalciferol in kidney.
• This step needs the presence of PTH
Role of Calcium ion in Regulating 1,25-
dihydroxycholecalciferol
• When blood calcium level increases it inhibits the formation of 1,25
dihydroxycholecalciferol.
The mechanism involved in the inhibition of the formation of1,25
dihydroxycholecalciferol is as follows:
• Increase in calcium ion concentration directly suppresses the
conversion of 25-hydroxycholecalciferol which is very mild.
• Increase in calcium ions concentration decreases the PTH secretion
which in turn, suppresses the conversion of 25-
dihydroxycholecalciferol into 1,25-dihydroxycholecalciferol.
• This regulates the calcium ion concentration of plasma itself
indirectly.
CALCIUM DEFICIENCY DISORDERS
Disorders of parathyroid glands are of two types:
• I. Hypoparathyroidism
• II. Hyperparathyroidism.
HYPOPARATHYROIDISM – HYPOCALCEMIA
• Hyposecretion of PTH is called hypoparathyroidism. It leads to
hypocalcemia (decrease in blood calcium level).
• Causes for Hypoparathyroidism
1. Surgical removal of parathyroid glands (parathyroidectomy)
2. Removal of parathyroid glands during surgical removal of thyroid gland
(thyroidectomy)
3. Autoimmune disease
4. Deficiency of receptors for PTH in the target cells. In this, the PTH
secretion is normal or increased but the hormone cannot act on the
target cells. This condition is called pseudohypoparathyroidism.
HYPERPARATHYROIDISM –HYPERCALCEMIA
• Hypersecretion of PTH is called hyperparathyroidism. It results in
hypercalcemia(increase in blood plasma level) because of increased
resorption of calcium from bones.
• Hyperparathyroidism is of three types:
• 1. Primary hyperparathyroidism
• 2. Secondary hyperparathyroidism
• 3. Tertiary hyperparathyroidism
Signs and symptoms of hypercalcemia
i. Depression of the nervous system
ii. Sluggishness of reflex activities
iii. Reduced ST segment and QT interval in ECG
iv. Lack of appetite
v. Constipation.
• Depressive effects of hypercalcemia are noticed when the blood
calcium level increases to 12 mg/dl. The condition becomes severe
with 15 mg/dl and it becomes lethal when blood calcium level
reaches 17 mg/dl .
APPLIED PHYSIOLOGY – DISEASES OF BONE
Osteoporosis
Osteoporosis is the bone disease characterized by the loss of bone
matrix and minerals. Osteoporosis means ‘porous bones’.
• Manifestations of osteoporosis
Loss of bone matrix and minerals leads to loss of bone strength,
associated with architectural deterioration of bone tissue. Ultimately,
the bones become fragile with high risk of fracture. Commonly
affected bones are vertebrae and hip.
Rickets
• Rickets is the bone disease in children, characterized by inadequate
mineralization of bone matrix.
• It occurs due to vitamin D deficiency affecting the reabsorption of
calcium and phosphorus from renal tubules, resulting in calcium
deficiency causing inadequate mineralization of in growing bones.
Osteomalacia
Rickets in adults is called osteomalacia or adult rickets.
Causes of osteomalacia
• Osteomalacia occurs because of deficiency of vitamin D. It also occurs due
to prolonged damage of kidney (renal rickets).
Features of osteomalacia
i. Vague pain
ii. Tenderness in bones and muscles
iii. Myopathy leading to waddling gait. In waddling gait, the feet are wide
apart and walk resembles that of a duck
iv. Occasional hypoglycemic tetany.
CONCLUSION
Calcium being one the most abundant cation of the body. Calcium
plays an essential role in the growth and maintenance of body
metabolism.
REFERENCES
• Essentials of Medical Physiology, K. Sembulingam, 6th Edition
• Fundamentals of Biochemistry , A.C. Deb, 7th Edition
• Textbook of Pathology , Harsh Mohan, 8th Edition.
Calcium Metabolism

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Calcium Metabolism

  • 1. Presented by : Faisal Noor Ahmad PG 1st year CALCIUM METABOLISM Under the Guidance of : Dr. Ravishankar T.L Dr. Amit Tirth Dr. Vaibhav Tandon Dr. Smita Chandra
  • 2. INTRODUCTION Calcium is very essential for many activities in the body such as- • Neuronal activity • Skeletal muscle activity • Cardiac activity • Smooth muscle activity • Secretory activity of glands • Coagulation of blood
  • 3. Normal Range : 9- 11 mg% • Daily Requirement • Adults : 500 mg/day • Children: 1200 mg/day • Pregnancy and Lactation: 1500 mg/day • 99% of calcium is present in bone and rest in plasma. Types of Calcium : 1. Calcium in plasma 2. Calcium in bone
  • 4. 1. Calcium in Plasma Calcium is present in three forms in Plasma: • Ionized or diffusible calcium • Non ionized or non-diffusible calcium • Calcium bound to albumin
  • 5. IONISED CALCIUM • Found freely in plasma • Forms about 50% of plasma calcium • Essential for vital functions like a. Neuronal activity b. Muscle contraction c. Cardiac activity d. Secretions in gland e. Blood coagulations
  • 6. Non Ionized Form • 8-10% of plasma calcium • For e.g. Calcium Bicarbonate •CALCIUM BOUND TO ALBUMIN • About 40-42% of calcium is bound with plasma protein
  • 7. 2. CALCIUM IN BONES Calcium in bones is of two types- • Small quantity of readily exchangeable activity • Large quantity of stable calcium The exchangeable calcium is the one that is removed from the bones. Helps to maintain the plasma calcium level The stable calcium is the one ,which is constantly removed and deposited in the bones Helps in bone remodeling
  • 8. Schematic Diagram Showing Calcium Metabolism
  • 9. Regulation of Blood Calcium Level • Absorbed from GI tract into blood and distributed to various parts of the body. • Depending upon the blood level , the calcium is either deposited in the bone or removed from the bone. • All these processes are finely regulated mainly by three hormones I. Parathormone II. 1,25 dihydroxycholecalciferol III. Calcitonin
  • 10. I. PARATHORMONE • Protein hormone • Secreted by Parathyroid gland • Increases the blood calcium level by mobilizing calcium from bone(resorption) II. 1,25 DIHYDROXYCHOLECALCIFEROL • Steroid hormone • Synthesized from vitamin D • Increases blood calcium level by increasing the calcium absorption from small intestine
  • 11. III. CALCITONIN • Calcitonin is secreted by parafollicular cells of thyroid gland. • Thyroid gland is a calcium-lowering hormone. • It reduces the blood calcium level mainly by decreasing bone resorption.
  • 12.  Action of Calcitonin- On Bone • Calcitonin facilitates deposition of calcium on bones(osteoblastic activity) • Also suppresses the activity of osteoclasts which are responsible for resorption of calcium from bones. • Inhibits the development of new osteoclasts in bones On Kidney • Calcitonin increases the excretion of calcium through urine ,by inhibiting the reabsorption of calcium from the renal tubules On Intestine • Prevents the absorption of calcium from intestine into blood
  • 13. Schematic Diagram showing regulation of Blood Calcium Level
  • 14. ACTIONS OF PARATHORMONE • Maintains the blood calcium level by acting on bones kidneys and GI tract • Parathyroid hormone increases : Resorption of calcium from the bones Reabsorption of calcium from renal tubules Absorption of calcium from GI tract
  • 15.  On Bone • PTH is responsible for the resorption of calcium from bones by stimulating both osteoblasts and osteoclasts of the bone. • Resorption of calcium from bone occurs in two phases : a. Rapid phase b. Slow phase a) RAPID PHASE Occurs within minutes after the release of PTH from parathyroid glands. After reaching the bone ,PTH gets attached with the receptors on the cell membrane of osteoblasts and osteocytes.
  • 16. • The hormone- receptor complex increases the permeability of the membrane of these cells for calcium ions. • Increases the calcium pump mechanism allowing calcium ions to move from these cells into the plasma. b) SLOW PHASE: Slow phase of calcium resorption from bone is by activation of osteoclasts. When osteoclasts are activated by PTH ,some proteolytic enzymes are released from the lysosomes of these cells. Apart from the proteolytic enzymes ,several acids such as citric acid and lactic acid are also released
  • 17. • All these substances digest or dissolve the organic matrix of the bone, releasing the calcium ions. calcium ions slowly move into the plasma. Thus, PTH releases calcium from bones by activating osteoclasts.
  • 18.  On kidneys • PTH increases the reabsorption of calcium from the renal tubule along with magnesium ions and hydrogen ions. • Calcium is reabsorbed from DCT and PCD. • PTH also increases the formation of 1,25- dihydroxycholecalciferol (activated form of vitamin D) which is also absorbed in the PCT. ON GIT • PTH increases the absorption of calcium ions from the GI tract indirectly. • Increases the formation of 1,25-dihydroxycholecalciferol in kidneys. This vitamin in turn increases absorption of calcium ions from GIT.
  • 19. Activation of vitamin D • Important form of vitamin D is vitaminD3 • Also known as cholecalciferol • Synthesized in skin from 7-dehydrocholestrol by the action of UV rays from the sunlight. • Also obtained from dietary sources FIRST STEP • Cholecalciferol is converted into 25-hydroxycholecalciferol in the liver. • This process is limited and is inhibited by 25-hydroxycholecalciferol itself by feedback mechanism.
  • 20.  This inhibition is essential for two reasons: -Regulation of the amount of active vitamin D -Storage of vitamin D for months together • If vitamin D3 is converted into 25 hydroxycholecalciferol without getting properly inhibited , it will remain in the body only for 2-5 days. • But Vitamin D3 is stored in liver for several months. SECOND STEP- • 25-hydroxycholecalciferol is converted into 1,25- dihydroxycholecalciferol in kidney. • This step needs the presence of PTH
  • 21. Role of Calcium ion in Regulating 1,25- dihydroxycholecalciferol • When blood calcium level increases it inhibits the formation of 1,25 dihydroxycholecalciferol. The mechanism involved in the inhibition of the formation of1,25 dihydroxycholecalciferol is as follows: • Increase in calcium ion concentration directly suppresses the conversion of 25-hydroxycholecalciferol which is very mild. • Increase in calcium ions concentration decreases the PTH secretion which in turn, suppresses the conversion of 25- dihydroxycholecalciferol into 1,25-dihydroxycholecalciferol. • This regulates the calcium ion concentration of plasma itself indirectly.
  • 23. Disorders of parathyroid glands are of two types: • I. Hypoparathyroidism • II. Hyperparathyroidism.
  • 24. HYPOPARATHYROIDISM – HYPOCALCEMIA • Hyposecretion of PTH is called hypoparathyroidism. It leads to hypocalcemia (decrease in blood calcium level). • Causes for Hypoparathyroidism 1. Surgical removal of parathyroid glands (parathyroidectomy) 2. Removal of parathyroid glands during surgical removal of thyroid gland (thyroidectomy) 3. Autoimmune disease 4. Deficiency of receptors for PTH in the target cells. In this, the PTH secretion is normal or increased but the hormone cannot act on the target cells. This condition is called pseudohypoparathyroidism.
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  • 26. HYPERPARATHYROIDISM –HYPERCALCEMIA • Hypersecretion of PTH is called hyperparathyroidism. It results in hypercalcemia(increase in blood plasma level) because of increased resorption of calcium from bones. • Hyperparathyroidism is of three types: • 1. Primary hyperparathyroidism • 2. Secondary hyperparathyroidism • 3. Tertiary hyperparathyroidism
  • 27. Signs and symptoms of hypercalcemia i. Depression of the nervous system ii. Sluggishness of reflex activities iii. Reduced ST segment and QT interval in ECG iv. Lack of appetite v. Constipation. • Depressive effects of hypercalcemia are noticed when the blood calcium level increases to 12 mg/dl. The condition becomes severe with 15 mg/dl and it becomes lethal when blood calcium level reaches 17 mg/dl .
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  • 29. APPLIED PHYSIOLOGY – DISEASES OF BONE
  • 30. Osteoporosis Osteoporosis is the bone disease characterized by the loss of bone matrix and minerals. Osteoporosis means ‘porous bones’. • Manifestations of osteoporosis Loss of bone matrix and minerals leads to loss of bone strength, associated with architectural deterioration of bone tissue. Ultimately, the bones become fragile with high risk of fracture. Commonly affected bones are vertebrae and hip.
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  • 32. Rickets • Rickets is the bone disease in children, characterized by inadequate mineralization of bone matrix. • It occurs due to vitamin D deficiency affecting the reabsorption of calcium and phosphorus from renal tubules, resulting in calcium deficiency causing inadequate mineralization of in growing bones.
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  • 34. Osteomalacia Rickets in adults is called osteomalacia or adult rickets. Causes of osteomalacia • Osteomalacia occurs because of deficiency of vitamin D. It also occurs due to prolonged damage of kidney (renal rickets). Features of osteomalacia i. Vague pain ii. Tenderness in bones and muscles iii. Myopathy leading to waddling gait. In waddling gait, the feet are wide apart and walk resembles that of a duck iv. Occasional hypoglycemic tetany.
  • 35. CONCLUSION Calcium being one the most abundant cation of the body. Calcium plays an essential role in the growth and maintenance of body metabolism.
  • 36. REFERENCES • Essentials of Medical Physiology, K. Sembulingam, 6th Edition • Fundamentals of Biochemistry , A.C. Deb, 7th Edition • Textbook of Pathology , Harsh Mohan, 8th Edition.