Calcium is essential for many bodily functions like bone formation, muscle contraction, nerve signaling etc. 99% of calcium is stored in bones and remaining 1% is present in extracellular fluids. Calcium level is tightly regulated by parathyroid hormone, calcitriol (active form of vitamin D), and calcitonin. These hormones work to maintain calcium between 9-11 mg/dL by mobilizing calcium from bones and kidneys and absorbing it from intestines. An imbalance in these regulatory hormones can lead to conditions like osteoporosis and rickets.

1. BLOOD
CALCIUM
BY
ARCHANA.B
FIRST YEAR PG

2. Introduction:
Total calcium in the human body is about 1-1.5 kg of
which 99% is seen in the bones and 1% in the
extracellular fluids.
If the daily requirements of any element is more than
100mg then such elements are called major elements or
macro minerals.

3. Minerals present in our body are classified into
Major minerals ( macro minerals)
Trace elements (micro minerals)

4. IMPORTANCE OF CALCIUM
Calcium is very essential for many activities in the body such as:
1. Bone and teeth formation
2. Neuronal activity
3. Skeletal muscle activity
4. Cardiac activity
5. Smooth muscle activity
6. Secretory activity of the glands
7. Cell division and growth
8. Coagulation of blood

5. Sources of calcium:
•Milk is a good source of calcium.
•Egg, fish and vegetables are medium sources
•Cereals contain a small quantity of calcium which makes up the
major source of calcium for the indian population.

6. Calcium is available in several foodstuffs.
Percentage of calcium in different food substance is:
• Whole milk = 10%
• Low fat milk = 18%
• Cheese = 27%
• Other dairy products = 17%
• Vegetables = 7%
Other substances such as meat, egg, grains, sugar,
coffee, tea, chocolate, etc. = 21%
Besides dietary calcium, blood also gets
calcium from bone by resorption.

7. Adult
500mg/day
Children
1200mg/day
Pregnancy &
lactation
1500mg/day
Daily requirement:
After te age of 50 there is general tendency of
osteoporesis that can be prevented by increased calcium
intake with vitamin D.

8. TYPES OF CALCIUM:
Calcium in Plasma:
Calcium is present in three forms in plasma:
I . Ionized or diffusible calcium: Found freely in plasma and forms
about 50% of plasma calcium. It is essential for vital functions such as
neuronal activity, muscle contraction, cardiac activity, secretions in
the glands, blood coagulation, etc.
II. Non-ionized or non-diffusible calcium: Present in non-ionic form
such as calcium bicarbonate.It is about 8% to 10% of plasma calcium
III. Calcium bound to albumin: Forms about 40% to 42% of plasma
calcium.

9. Calcium in Bones
Calcium is constantly removed from bone and deposited in bone.
Bone calcium is present in two forms:
I. Rapidly exchangeable calcium or exchangeable calcium: Available
in small quantity in bone and helps to maintain the plasma calcium level
II. Slowly exchangeable calcium or stable calcium: Available in
large quantity in bones and helps in bone remodeling.

10. Absorption and excretion of calcium:
Calcium taken through dietry sources is absorbed from the GI tract into
blood and distributed to various parts of the body.
Depening upon the blood level the calcium is either deposited in the bone
or removed from the bone
Calcium is excreated from the body through urine and feces.

11. Absorption from GI tract:
Calcium is absorbed from duodenum by carrier
mediated active transport and from the rest of the
small intestine by facilitated diffusion.
Vit- D is essential for absorption of calcium from the
GI tract.

12. Excretion:
About 1000mg of calcium is excreated daily. While passing through
kidney large quantity of calcium is filtered in the glomerulus
From the filterate 98-99% of calcium is reasorbed from the renal
tubles into the blood and only and small quantity is excreated in the
urine
Most of the filtered cacium is resorbed in the distal convoluted
tubules and proximal part of the collecting duct

13. In distal convuluted tubule parathormone
increases the resorption of calcium
In collecting duct vitamine D increases
the the calcium resorption and calcitonin
decreases resorption.
Out of this 900mg is excreated through
feces and 100 mg through urine

14. Process of calcium metabolism

15. REGULATION OF BLOOD CALCIUM LEVEL
Blood calcium level is regulated mainly by three
hormones:
1. Parathormone
2. 1,25-dihydroxycholecalciferol (calcitriol)
3. Calcitonin.

16. Regulation of blood calcium:

17. In calcium metabolism
Parathormone

18. Parathormone is a protein hormone secreted by parathyroid gland
and its main function is to increase the blood calcium level by
mobilizing calcium from bone.
Parathormone secreted by parathyroid gland is essential for the
maintenance of blood calcium level within a very narrow critical
level.
Maintenance of blood calcium level is necessary because calcium is
an important inorganic ion for many physiological functions

19. Human beings have four parathyroid glands, which are
situated on the posterior surface of upper and lower
poles of thyroid gland .

20. ACTIONS OF PARATHORMONE ON BLOOD CALCIUM LEVEL
Primary action of PTH is to maintain the blood calcium
level within the critical range of 9 to 11 mg/dL. The blood
calcium level has to be maintained critically because, it
is very important for many of the activities in the body.
PTH maintains blood calcium level by acting on:
1. Bones
2. Kidney
3. Gastrointestinal tract.

21. 1. On Bone
Parathormone enhances the resorption of calcium from
the bones (osteoclastic activity) by acting on
osteoblasts and osteoclasts of the bone.
Resorption of calcium from bones occurs in two
phases:
i. Rapid phase
ii. Slow phase.

23. 2. On Kidney
PTH increases the reabsorption of calcium from the renal tubules along with
magnesium ions and hydrogen ions. It increases calcium reabsorption mainly
from distal convoluted tubule and proximal part of collecting duct.
PTH also increases the formation of 1,25-dihydroxycholecalciferol
(activated form of vitamin D) from 25-hydroxycholecalciferol in kidneys.

24. 3. On Gastrointestinal Tract
PTH increases the absorption of calcium ions from the GI tract indirectly. It
increases the formation of 1,25-dihydroxycholecalciferol in the kidneys. This
vitamin, in turn increases the absorption of calcium from GI tract. Thus, the
activated vitamin D is very essential for the absorption of calcium from the GI
tract. And PTH is essential for the formation of activated vitamin D.

25. Role of PTH in the activation of vitamin D
Vitamin D is very essential for calcium absorption from the GI
tract. But vitamin D itself is not an active substance. Instead,
vitamin D has to be converted into 1, 25-dihydroxycholecalciferol in
the liver and kidney in the presence of PTH. The 1,25-
dihydroxycholecalciferol is the active product.

26. Role of PTH on Blood Level of Calcium
Blood level of calcium is the main factor regulating the secretion of
PTH.
Parathormone secretion is inversely proportional to blood calcium level.
Increase in blood calcium level decreases PTH secretion.

27. Conditions when PTH secretion decreases are:
1. Excess quantities of calcium in the diet
2. Increased vitamin D in the diet
3. Increased resorption of calcium from the bones, caused by
some other factors such as bone diseases.
On the other hand, decrease in calcium ion concentration of
blood increases PTH secretion, as in the case of rickets,
pregnancy and in lactation.

28. In calcium metabolsm
1,25-dihydroxycholecalciferol
(calcitriol)

29. Calcitriol is a steroid hormone synthesized in kidney.
It is the activated form of vitamin D. Its main
action is to increase the blood calcium level by
increasing the calcium absorption from the small
intestine

30. Activation of vitamin D
•There are various forms of vitamin D. But, the most important one is vitamin
D3. It is also known as cholecalciferol.
•Vitamin D3 is synthesized in the skin from 7-dehydrocholesterol, by the
action of ultraviolet rays from the sunlight. It is also obtained from
dietary sources.
•The activation of vitamin D3 occurs in two steps

31. First step
Cholecalciferol (vitamin D3) is converted into 25-hydroxycholecalciferol in
the liver. This process is limited and is inhibited by 25-hydroxycholecalciferol
itself by feedback mechanism.

32. Second step
25-hydroxycholecalciferol is converted into
1,25- dihydroxycholecalciferol (calcitriol) in
kidney. It is the active form of vitamin D3.
This step needs the presence of PTH.

33. Role of Calcium Ion in Regulating 1, 25-Dihydroxycholecalciferol
•When blood calcium level increases, it inhibits the formation of
1,25 dihydroxycholecalciferol.
•Increase in calcium ion concentration decreases the PTH secretion, which in
turn suppresses the conversion of 25-hydroxycholecalciferol into 1,25-
dihydroxycholecalciferol.

35. In calcium metabolism
CALCITONIN

36. Calcitonin 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

38. ACTIONS OF CALCITONIN On Blood Calcium Level
Calcitonin plays an important role in controlling the blood calcium
level. It decreases the blood calcium level and thereby
counteracts parathormone.
Calcitonin reduces the blood calcium level by acting on bones,
kidneys and intestine.

39. On bones
Calcitonin stimulates osteoblastic activity and facilitates the
deposition of calcium on bones. At the same time, it suppresses the
activity of osteoclasts and inhibits the resorption of calcium from
bones. It inhibits even the development of new osteoclasts in bones.
On kidney
Calcitonin increases excretion of calcium through urine, by inhibiting the
reabsorption from the renal tubules.
On intestine
Calcitonin prevents the absorption of calcium from intestine into the
blood.

40. Effects of Other Hormones
In addition to the above mentioned three
hormones, growth hormone and
glucocorticoids also influence the calcium
level.
Glucocorticoids(cortisol)
decrease blood calcium by
inhibiting intestinal
absorption and increasing
the renal excretion of
calcium.

42. In blood calcium regulation
Other factors

43. Phosphorus:
•There is a reciprocal relationship of calcium with phosphorus.
•Ionic products of calcium and phosphrous in the serum is is kept
as a constant i.e, Calcium= 10mg/dL and Phosohorus = 4mg/dL.
•When phosphorus content in the blood is increased the calcium
content is lowered (tetany)
Serum proteins:
•In hypoalbuminemia the total calcium is decreased.

44. Alkalosis and acidosis:
•Alkalosis favors binding of more calcium with
proteins with constant lowering of ionised
calcium in the serum so calcium deficiency may
be manifested
•Acidosis favors ionisation of calcium.

45. FUNCTIONS
OF CALCIUM

46. Activation of enzymes:
Many hormones act by increasing
the calcium ion, which fucntions
as second messenger along
with another protein called
calmodulin or troponin C.
Calmodulin is present in smooth muscles
and troponin C is present in skeletal muscles. Calcium-calmodulin complex
activates various enzymes in the cell, which cause the physiological
responses.
Eg: myosin kinase in smooth muscle.
c
Ca++ + Calmodulin
Ca- bound-
calmodulin
Kinase Active
kinaseEnzyme Phosphorylated
enzyme
Biological effect

47. Muscles:
Sarcotubular system is a system of membranous
structures in the form of vesicles and tubules
in the sarco plasm of the muscle fiber.
It surrounds the myofibrils embedded
in the sarcoplasm
Sarcotubular system is formed mainly by two
types of structures:
1. T tubules
2. L tubules or sarcoplasmic reticulum.

48. Calcium mediates excitation and contraction of muscle fibres.
An ATP dependent calcium pump also functions to regulate muscle
contraction.
In resting the concentration of calcium ions around the muscle fibres is
low after stimulation there is sudden release of calcium ions that triggers
muscle contraction.
Excitation-
contraction
coupling

49. Muscle
relaxation

50. Nerve conduction:
Calcium is necessary for transmission
of nerve impulses from the pre
synaptic to post synaptic region

51. Secretion of hormones:
Calcium mediates secreation of various hormones like insulin,
parathyroid,calcitonin, adrenalin etc.,
Calcium acts as a cholagogue that is it incrases the release of bile
into the intestine from the gall bladder.

52. Prostaglandins increase the force of uterine contractions by
elevating the concentration of calcium ions in the smooth muscle
fibers of uterus.
Calcium ions increase the release of serotonin, which facilitates
the synaptic transmission to a great extent, leading to memory
storage

53. Maintenance of Milk Secretion or Galactopoiesis
Galactopoiesis depends upon the hormones like growth hormone,
thyroxine and cortisol, which are essential for continuous supply of
glucose, amino acids, fatty acids, calcium and other substances
necessary for the milk production
BITTER TASTE RECEPTOR
Bitter receptor is a G-protein coupled
receptor . In bitter receptor, the sour
substances activate phospholipase C
through G proteins. It causes production
of inositol triphosphate (IP3), which
initiates depolarization by releasing
calcium ions.

54. Mineralization
Mineralization is the process by which the minerals are
deposited on bone matrix.
Mineralization starts about 10 to 12 days after the formation of
osteoid. First, a large quantity of calcium phosphate is deposited.
Afterwards, the hydroxide and bicarbonate ions are gradually added
causing the formation of hydroxyapatite crystals.
The process of mineralization is accelerated by the
enzyme alkaline phosphatase, secreted by osteoblast.
The process also requires the availability of adequate
amount of calcium and phosphate in the ECF.

55. Vascular permiability:
Calcium decreases the passage of serum through capillaries.
Thus calcium is clinically used to reduce allergic exudates.
Myocardium:
Ca2+ prolongs systole
Calpains:
Calpains are calcium dependent cysteine proteases that modulate cellular
function.
Calpains are involved in apoptosis process also.

56. Calcium in blood

57. Inorganic substances present in body fluids are sodium, potassium,
calcium, magnesium, chloride, bicarbonate, phosphate and sulfate.
Substance ECF ICF
Calcium 5 mEq/L 1 mEq/L
Platelet Granules
Granules present in cytoplasm of platelets are of two
types:
1. Alpha granules
2. Dense granules

58. Adhesiveness is the property of sticking to a rough surface.
factors which accelerate adhesiveness are collagen, thrombin, ADP,
Thromboxane A2, calcium
ACTIVATORS OF PLATELETS
1. Collagen, which is exposed during damage of blood vessels
2. von Willebrand factor
3. Thromboxane A2
4. Platelet-activating factor
5. Thrombin
6. ADP
7. Calcium ions
8. P-selectin: Cell adhesion molecule secreted from
endothelial cells
9. Convulxin: Purified protein from snake venom.

59. FACTORS INVOLVEDIN BLOODCLOTTING
Thirteen clotting factors are identified:
Factor I Fibrinogen
Factor II Prothrombin
Factor III Thromboplastin (Tissue factor)
Factor IV Calcium
Factor V Labile factor (Proaccelerin or accelerator globulin)
Factor VI Presence has not been proved
Factor VII Stable factor
Factor VIII Antihemophilic factor (Antihemophilic globulin)
Factor IX Christmas factor
Factor X Stuart-Prower factor
Factor XI Plasma thromboplastin antecedent
Factor XII Hageman factor (Contact factor)
Factor XIII Fibrin-stabilizing factor (Fibrinase).

60. Intrinsic and
extrinsic pathways:

61. Anti coagulants’ action:
1. HEPARIN:
Heparin is a naturally produced anticoagulant in the body.
It is produced by mast cells which are the wandering cells present
immediately outside the capillaries in many tissues or organs that contain more
connective tissue.
Commercial preparation is available in liquid form or dry form as sodium,
calcium, ammonium or lithium salts.
2. EDTA
Ethylenediaminetetraacetic acid (EDTA) is a strong anticoagulant.
These substances prevent blood clotting by removing calcium from blood.

62. OXALATE COMPOUNDS
Oxalate compounds prevent coagulation by forming
calcium oxalate, which is precipitated later. Thus,
these compounds reduce the blood calcium level.
CITRATES:
Citrate combines with calcium in blood to form
insoluble calcium citrate. Like oxalate, citrate also
removes calcium from blood and lack of calcium
prevents coagulation.

63. PROTHROMBIN TIME
Prothrombin time (PT) is the time taken by blood to clot after
adding tissue thromboplastin to it.
Blood is collected and oxalated so that, the calcium is
precipitated and prothrombin is not converted into thrombin.
Thus, the blood clotting is prevented.
Then a large quantity of tissue thromboplastin with calcium is
added to this blood.
Calcium nullifies the effect of oxalate. The tissue
thromboplastin activates prothrombin and blood clotting occurs.

64. PARTIAL PROTHROMBIN TIME OR ACTIVATED
PROTHROMBIN TIME
Partial prothrombin time (PPT) is the time taken for the
blood to clot after adding an activator such as phospholipid,
along with calcium to it. It is also called activated partial
prothrombin time (APTT). This test is useful in monitoring
the patients taking anticoagulant drugs.
It is carried out by observing clotting time after adding
phospholipid, a surface activator and calcium to a patient’s
plasma.

65. In calcium metabolism
Disorders

66. Rigor: Rigor refers to shortening and stiffening of muscle fibers.
Calcium rigor: Due to increased calcium content.
It is reversible.
Rigor mortis: Soon after death, the cell membrane becomes highly
permeable to calcium enters the muscle fibers and promotes the formation
of actomyosin complex resulting in contraction of the Muscles.
Stoppage of the heart in systole, due to hypercalcemia
is called the calcium rigor.
EATON-LAMBERT SYNDROME
Eaton-Lambert syndrome is also an autoimmune disorder of neuromuscular
junction. It is caused by antibodies to calcium channels in axon terminal.

67. HYPOCALCEMIA
decrease in blood calcium level.
Hypocalcemic Tetany
Tetany is an abnormal condition characterized by violent and painful
muscular spasm (spasm = involuntary muscular contraction), particularly
in feet and hand.
It is because of hyperexcitability of nerves and skeletal muscles due to
calcium deficiency.

68. Cardiovascular changes
i. Dilatation of the heart
ii. Prolonged duration of ST segment and QT interval in ECG
iii. Arrhythmias (irregular heartbeat)
iv. Hypotension
v. Heart failure.

69. Other features
i. Decreased permeability of the cell membrane
ii. Dry skin with brittle nails
iii. Hair loss
iv. Grand mal, petit mal or other seizures
v. Signs of mental retardation in children or
dementia in adults

70. Hypercalcemia
Hypercalcemia is the increase in plasma calcium level.
It occurs in hyperparathyroidism because of increased
resorption of calcium from bones.
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.
It increases the excitability and contractility of the heart
muscle. In clinical conditions, the effect of hypercalcemia
is very rare.

71. 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.

72. Patients with chronic periodontitis present
increased risk for osteoporosis: A population-
based cohort study in Taiwan. - Mau LP et al.
JPR-2017
Association of osteoporosis and bone medication
with the periodontal condition in elderly women.-
Penoni Dc et al- 2016

73. Rickets
Rickets is the bone disease in children,
characterized by inadequate mineralization of
bone matrix.
It occurs due to vitamin D deficiency.
Deficiency of vitamin D affects the reabsorption
of calcium and phosphorus from renal tubules, resulting in calcium
deficiency.
It causes inadequate mineralization of epiphyseal growth plate in
growing bones.

74. 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).

75. 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.

76. Other conditions related to calcium:
Osteo petrosis
Hyper thyroidism
Hypo thyroidism
Kidney stones
Gall stones (Cholelithiasis)
Hyper-reflexia and convulsions
Carpopedal spasm
Laryngeal stridor