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Calcium Metabolism
INDRA RUKMANA TRI PRATISTHA
ORTHOPAEDI DAN TRAUMATOLOGI RSUP SANGLAH
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Calcium Metabolism
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.
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Normal Value
In a normal young healthy adult, there is about
1,100 g of calcium in the body.
It forms about 1.5% of total body weight.
99% of calcium is present in the bones and teeth
and the rest is present in the plasma.
Normal blood calcium level ranges between 9
and 11 mg/dL.
 Distribution of calcium 5

Skeleton - 99%

Muscle 0.3%

Other tissues 0.7%

800mg of calcium is
absorbed /day
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Types Of Calcium
Calcium in Plasma
Calcium is present in three forms in plasma:
1. Ionized or diffusible calcium:
Found freely in plasma and forms about 50% of
plasma calcium.
2. Non-ionized or non-diffusible calcium:
Present in non-ionic form such as calcium
bicarbonate.
It is about 8% to 10% of plasma calcium
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3. Calcium bound to albumin:

Forms about 40% to 42% of plasma calcium.
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Calcium in Bones
Calcium is constantly removed from bone and
deposited in bone.
Bone calcium is present in two forms:
1. Rapidly exchangeable calcium/exchangeable
calcium which is available in small quantity in bone
and helps to maintain the plasma calcium level
2. Slowly exchangeable calcium /stable calcium
which is available in large quantity in bones and
helps in bone remodeling.
Calcium functions (Bone)
Osteoclasts (bone cells)
remodel the bone by
dissolving or resorbing bone
Osteoblasts (bone forming
cells) synthesize new bone
to replace the resorbed bone
Found on the outer surfaces
of the bones and in the bone
cavities
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 Calcium Homeostasis 1
1
storage kidney
bone
calcium deposition Blood
Ca++
calcium resorption
1000 g
Ca++
stored in
bone
intake Ca++ Ca++
absorbed into excretion lost in urine
Calcium in blood
the diet
calcium lost in feces
small intestine
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Source Of Calcium 2
Dietary Source
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%
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From Bones
Besides dietary calcium, blood also gets calcium
from bone by resorption.
Daily Requirements Of Calcium 1
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1 to 3 years = 500 mg
4 to 8 years = 800 mg
9 to 18 years = 1,300 mg
19 to 50 years = 1,000 mg
51 years and above = 1,200 mg
Pregnant ladies and lactating mothers = 1,300
mg
Absorption And Excretion Of 1
Calcium 6
Calcium taken through dietary sources is
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 (resorption).
Calcium is excreted from the body through
urine and feces
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Absorption from Gastrointestinal Tract
Calcium is absorbed from duodenum by carrier
mediated active transport and from the rest of
the small intestine, by facilitated diffusion.
Vitamin D is essential for the absorption of
calcium from GI tract.
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Excretion
While passing through the kidney, large quantity
of calcium is filtered in the glomerulus.
From the filtrate, 98% to 99% of calcium is
reabsorbed from renal tubules into the blood.
Only a small quantity is excreted through urine.
Most of the filtered calcium is reabsorbed in the
distal convoluted tubules and proximal part of
collecting duct.
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In distal convoluted tubule, parathormone increases
the reabsorption.
In collecting duct, vitamin D increases the
reabsorption and calcitonin decreases reabsorption
About 1,000 mg of calcium is excreted daily.
Out of this, 900 mg is excreted through feces and
100 mg through urine
 Absorption and excretion factors 2
Absorption increased by: Excretion increased by: 0
Body need Low parathyroid hormone (PTH)
Vitamin D High extracellular fluid volume
Protein High blood pressure
Lactose
Low plasma phosphate
Acid medium
Metabolic alkalosis
Absorption decreased by:
Excretion decreased by:
Vitamin D deficiency
Calcium-phosphorus imbalance - High parathyroid hormone
Oxalic acid
Low extracellular fluid volume
Phosphorous Low blood pressure
Dietary fiber High plasma phosphate
Excessive fat Metabolic acidosis
High alkalinity Vitamin D3
Also stresses and lack of exercise
Regulation Of Blood Calcium 2
Level 1
Blood calcium level is regulated mainly by three
hormones:
1. Parathormone
2. 1,25-dihydroxycholecalciferol (calcitriol)
3. Calcitonin.
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 Regulation

Compensatory responses to decreased plasma ionized calcium

concentration mediated by PTH & vitamin D
PTH regulates through 3 main effects:
By stimulating bone resorption

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By stimulating activation of vitamin D intestinal Ca reabsorption
By directly increasing renal tubular calcium reabsorption
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1. Parathormone
Parathormone is a protein hormone secreted by
parathyroid gland
Its main function is to increase the blood calcium
level by mobilizing calcium from bone
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2. 1,25-dihydroxycholecalciferol Calcitriol
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.
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3. Calcitonin
Calcitonin secreted by parafollicular cells of
thyroid gland.
It is a calcium-lowering hormone.
It reduces the blood calcium level mainly by
decreasing bone resorption.
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Effects of Other Hormones
In addition to the above mentioned three
hormones, growth hormone and glucocorticoids
also influence the calcium level.
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Growth hormone
Growth hormone increases the blood calcium
level by increasing the intestinal calcium
absorption.
It is also suggested that it increases the urinary
excretion of calcium.
However, this action is only transient.
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Glucocorticoids
Decrease blood calcium by inhibiting intestinal
absorption and increasing the renal excretion of
calcium
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 Interactions 3
2
Phosphate: calcium excretion in the urine
Caffeine: urinary and fecal excretion of calcium
Sodium: sodium intake, loss of calcium in urine
Dietary constituents: Phytic acid can reduce absorption
of calcium by forming an insoluble salt (calcium phytate)
Iron: calcium might have inhibitory effect on iron
absorption
 Three in Calcium 3
3 Sites Intestines, bones, blood. 3
3 hormones Parthormone, Calcitonin, Vitamin D.
3 chemical forms protein bound, ionic calcium, crystalline
form.
3 crystalline forms Hydroxyapatite(ha), calcium
pyrophosphate dihydrate(CPPD), Calcium
oxalate.
3 forms of pathological calcification dystrophic
calcification, metastatic calcification,
calcium stone (lithiasis)
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Phosphate
Metabolism
INDRA RUKMANA TRI PRATISTHA
ORTHOPAEDI DAN TRAUMATOLOGI RSUP SANGLAH
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Functions of phospHATE 5

Development of bone and teeth

Formation of high energy compounds
Required for formation of phospholipids,
phospho-proteins and DNA and RNA
Several enzymes and proteins are
activated by phosphorylation.
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Phosphate Metabolism 6
Phosphorus (P) is an essential mineral that is required
by every cell in the body for normal function.
Phosphorus is present in many food substances, such as
peas, dried beans, nuts, milk, cheese and butter.
Inorganic phosphorus (Pi) is in the form of the phosphate
(PO4).
The majority of the phosphorus in the body is found as
phosphate.
In body, phosphate is the most abundant intracellular
anion.
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Importance Of Phosphate
1. Phosphate is an important component of many
organic substances such as, ATP, DNA, RNA and
many intermediates of metabolic pathways
2. Along with calcium, it forms an important
constituent of bone and teeth
3. It forms a buffer in the maintenance of acid-base
balance.
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Normal Value
Total amount of phosphate in the body is 500 to
800 g.
Though it is present in every cell of the body,
85% to 90% of bodys phosphate is found in the
bones and teeth.
Normal plasma level of phosphate is 4 mg/dL.
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Regulation Of Phosphate Level
Blood phosphate level is regulated mainly by
three hormones:
1. Parathormone
2. Calcitonin
3. 1,25-dihydroxycholecalciferol (calcitriol).
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Parathormone
Parathormone stimulates resorption of phosphate
from bone and increases its urinary excretion.
It also increases the absorption of phosphate from
gastrointestinal tract through calcitriol.
The overall action of parathormone decreases the
plasma level of phosphate.
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Calcitonin
Calcitonin also decreases the plasma level of
phosphate by inhibiting bone resorption and
stimulating the urinary excretion.
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1,25-Dihydroxycholecalciferol Calcitriol
Calcitriol hormone increases absorption of
phosphate from small intestine.
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Effects of Other Hormones
Growth hormone and glucocorticoids also
influence the phosphate level.

1. Growth hormone
Increases the blood phosphate level by increasing
the intestinal phosphate absorption.
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2. Glucocorticoids
Decreases blood phos phate by inhibiting
intestinal absorption and increasing the renal
excretion of phosphate.
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VITAMIN D
INDRA RUKMANA TRI PRATISTHA
ORTHOPAEDI DAN TRAUMATOLOGI RSUP SANGLAH
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Vitamin - D 8
Fat soluble vitamin.
sunshine vitamin.
Structure is like Sterol.
Act as Hormone
Synthesized in skin
Regulate Calcium & Phosphorus metabolism
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Chemistry 9
It is available in 2 forms
D3 Cholecalciferol - Animal
D2 - Ergocalciferol- Plant
Both are provitamins
Active form : Calcitriol
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Synthesis 0
METABOLISM 5
Absorptio 1
n
Forms Site Mechanism

D2 Along with
Duodenum
lipids
&
Requires
D3 Jejunum
bile salts
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In Liver 2
Transport : From skin & intestine to liver with
DBP transport protein.
Hydroxylation: At 25th by Hepatic 25-
hydroxylase
Microsomal monooxygenase requires
cytochrome P-450, NADPH and molecular
oxygen.
Storage form: 25(OH)D3
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Activation 3
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In Kidney 4
Transport : From liver with DBP transport
protein.
Hydroxylation: At 1st by 1 -hydroxylase
Mitochondrial monooxygenase requires
cytochrome P-450, NADPH and molecular
oxygen.
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Regulation of synthesis 5
Ca+2
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Functions 6
Major :
Calcitriol regulate plasma calcium and
Phosphorus level
Development of Bones & Teeth

Other :
Cell Differentiation & inhibit cell proliferation
Immunity
Regulation of Calcium & phosphate 5
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Action of Calcitriol
on intestine

Action of Calcitriol on
bone
Action of Calcitriol on
kidney
Action of calcitriol on the intestine 5
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Increases the intestinal absorption of calcium
and phosphate
By increased synthesis of calcium binding
proteins calbindins & osteocalcin
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Calcitriol acts like a steroid 9
hormone.
mechanism of action resmble to
group II hormones
It enters the target cell and binds
to a cytoplasmic receptor.
The hormone receptor complex
interacts with DNA and
consequent transcription of
specific genes that code for
Calbindin
Action of calcitriol on the bone 6
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Both bone mineralization & bone resorption

Mineralization of bone by increased osteoblast
activity
Mobilization of calcium from bone and increased
plasma calcium and phosphate level
Action of calcitriol on the kidney 6
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Increased reabsorption of calcium and
phosphorus in the DCT
Decreased excretion of calcium and phosphorus
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sources 3
Sunlight
Fish
Liver oil
Eggs
Milk & milk products
Fortified cereals
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Daily requirment 4
Men and women- 200 IU(05g/day)

Pregnancy and lactation 400 IU(10g/day)

Infants & Children 400 IU(10g/day)

1microgram of vitamin D = 40 IU
Deficiency 6
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Inadequate supply insufficient exposure to sunlight in
persons who are bedridden for long time & cover their entire
body, strict vegetarians

Impaired absorption- obstructive jaundice

Impaired production of 25hydroxy vitamin D3 - liver disease

Impaired production of 1, 25 dihydroxy vitamin D3 kidney

disease
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Medications:
1. Phenobarbital and Phenytoin (used in epileptic patients)
can induce hepatic p450 enzymes to accelerate the
catabolism of vitamin D
2. Corticosteroids: convert vit-D into inactive metabolites.
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BONE
MINERALIZATION
INDRA RUKMANA TRI PRATISTHA
ORTHOPAEDI DAN TRAUMATOLOGI RSUP SANGLAH
Bone Matrix
Mineralization
Bone is composed of 50 to 70% mineral, 20 to
40% organic matrix, 5 to 10% water, and 3%
lipids.
The mineral content of bone is mostly
hydroxyapatite [Ca10(PO4)6(OH)2], with small
amounts of carbonate, magnesium, and acid
phosphate
 Matrix maturation is associated with expression
of alkaline phosphatase and several
noncollagenous proteins, including osteocalcin,
osteopontin, and bone sialoprotein. It is thought
that these calcium and phosphate binding
proteins help regulate ordered deposition of
mineral by regulating the amount and size of
hydroxyapatite crystals formed.
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