Calcium Metabolism

By: Kumsa K.(BSc., MSc.)

Introduction
•Calcium is an important mineral mainly found in bone and teeth.
•Dietary sources: It is widely distributed in food
substances such as milk, cheese, egg-yolk, beans, lentils, nuts, figs, cabbage.
•Body distribution: The total calcium of the body is 25-35 mols (100 g-170 g).
•About 99 per cent of it is found in bones.
•It exists as carbonate or phosphate of calcium.
•About 0.5 per cent in soft tissue and 0.1 per cent in ECF.
Cont.…
•The normal level of plasma calcium is 9-11 mg/dl.
•The calcium in plasma is of 3 types, namely:-
1. Ionized calcium (diffusible),
2. Protein bound calcium and
3. Complexed calcium, it is probably complexed with organic acids.
•About 40 per cent of total calcium is in ionised form.
•Albumin is the major protein with which calcium is bound.
•All the three forms of calcium in plasma remain in equilibrium with each other.
•Ionized calcium is physiologically active form of calcium.
Cont.….
• Absorption:
• Calcium is taken in the diet principally as
calcium phosphate, carbonate and tartarate.
• Unlike Na and K which are readily absorbed, the
absorption of Ca is rather incomplete.
• About 40 per cent of average daily dietary intake of
Ca is absorbed from the gut.
• Calcium is absorbed mainly from the duodenum
and first half of jejunum against electrical and
concentration gradients.
Cont.…

•MECHANISM
•Two mechanisms have been proposed for absorption
of calcium by gut mucosa.
1. Simple diffusion
2. An “ active ” transport process involving energy
and Ca++ pump.
•Both the processes require 1, 25-dihydroxy-D3
(calcitriol) which regulates the synthesis of Ca-
binding proteins and transport and also a Ca++-
dependent ATPase.
FACTORS AFFECTING ABSORPTION

•Various factors which influence the absorption of

calcium are discussed below:
•pH: An acidic pH favours calcium absorption
because the Ca-salts, particularly PO4 and carbonates
are quite soluble in acid solutions.
•In an alkaline medium, the absorption of calcium is
lowered due to the formation of insoluble tricalcium
PO4.
Cont..

Diet:-
•High protein diet: A high protein diet favours
absorption, 15 per cent of dietary Ca is absorbed.
• If the protein content is low, only 5 per cent may be
absorbed.
•Amino acids increase the solubility of Ca-salts and
thus its absorption.
•Lysine and arginine obtained from basic proteins
cause maximal absorption of Ca.
Cont.…

•Fatty acids: In malabsorption syndrome, fatty acids

are not absorbed properly.
•Fatty acids produce insoluble calcium soaps which are
excreted in faeces, thus, decreasing the Ca absorption.
•Sugars and organic acids: Organic acids produced by
microbial fermentation of sugars in the gut, increases the
solubility of Ca-salts and increases their absorption.
•Citric acid also may increase the absorption of calcium
Cont.…

• Pythic acid: Cereals contain pythic acid which

forms insoluble Ca-salts and decreases the
absorption of Ca.
• Oxalates: Oxalates present in vegetable like cabbage
and spinach forms insoluble calcium oxalates which
are excreted in the faeces, thus lowering the calcium
absorption.
• Fibres: Presence of excess of fibres in the diet
interferes with the absorption of calcium.
 Cont.….

•Minerals
– Phosphates: Excess of phosphates lower calcium absorption.
– Magnesium: High content of magnesium in the diet decreases
absorption of calcium.
– Ca:P ratio: A ratio of food Ca to P not more than 2:1 and not
less than 1:2 (ideal 1:1) is necessary for optimal absorption of
calcium.
•– Fe in diet: Food Fe may form insoluble ferric phosphates.
•These indirectly increases the Ca:P ratio in the gut beyond the
range of optimal absorption.
•Vitamin D: Promotes Ca absorption.
Cont.….

State of health of the individual and aging

•A healthy adult absorbs about 40 per cent of dietary calcium.
•Above the age of 60 years, there is a gradual decline
in the intestinal absorption of Ca.
•In sprue syndrome, the intestinal absorption of calcium
suffers due to formation of Ca-soap with FA which are
excreted in faeces.
Cont.…
Hormonal
•PTH (Parathormone): PTH directly cannot increase the
calcium absorption.
•But PTH stimulates “1, α hydroxylase” enzyme in the kidney
and increases the synthesis of 1, 25-(OH)2-D3 (calcitriol)
which enhances calcium absorption (refer to Vitamin D).
•Calcitonin: Calcitonin directly cannot affect Ca
absorption.
•Increased calcitonin level inhibits “1-α- hydroxylase” enzyme,
thus decreasing synthesis of calcitriol and Ca-absorption.
•Glucocorticoids: Diminishes intestinal transport of calcium.
Regulation of calcium homeostasis

• Three principal hormones are involved in calcium

homeostasis
• Vitamin D,
• Parathyroid hormone and
• Calcitonin
• Acting at three target organs,
• Intestine,
• Bone and
• Kidneys
Role of vitamin D in calcium homeostasis

• Cholecalciferol is synthesized from 7-

dehydrocholesterol in skin, under the influence of
sunlight.
• It is then hydroxylated at 25th position in liver and
further hydroxylated at the 1st position in kidney.
• The active derivative is called dihydroxy-
cholecalciferol or calcitriol
Cont…
• Actions of Vitamin D are :
• Enhances calcium absorption from the intestine
• Facilitates calcium absorption in the kidney
• Increases bone calcification and mineralization
• In excess, mobilizes bone calcium and phosphate
 Role of parathyroid hormone(PTH)

• PTH is secreted by chief cells in the four parathyroid

glands.
• Regulated by feedback mechanism in hypercalcemia
secretion is inhibited and calcium deposited in the bones.
• In hypocalcemia, PTH secretion is stimulated.
Cont….

• Action of PTH aimed at raising serum

calcium ,it:
• Increases bone calcium resorption (osteoclastic
activity).
• Increases renal calcium reabsorption by distal
renal tubules.
• Increase renal phosphate excretion by decreasing
tubule phosphate reabsorption.
Role of calcitonin

• It is secreted by parafollicular cells in the thyroid

gland.
• It tends to decrease serum calcium concentration .
• It acts as follows:
• Inhibit bone resorption
• Increases renal calcium excretion
• Its action is much weaker than PTH and Vitamin D
FUNCTIONS
•Calcification of Bones and Teeth
•Calcium plays a role in blood coagulation by
producing substances for thromboplastic activity of
blood.
•Calcium has a role in neuromuscular transmission.
•Calcium ions are needed for excitability of nerves.
•Calcium plays role in muscle contraction.
•It plays role as secondary or tertiary messenger in
hormone action.
•It plays role in permeability of gap junctions.
Phosphate

•Food Sources: Foods rich in phosphorus content are

cheese, milk, nuts, organ meats, egg.
•Body Distribution: Total body phosphate is about 25
mol (700 g).
•More than 85 per cent (600 g) is found in bones, 15
per cent in soft tissues and 1 per cent is found in ECF.
•About 5 g in brain and 2 g in blood is found.
•About 1.5 g of phosphate is required to be taken in
the diet daily.
Cont.

• Absorption: 90 per cent of daily dietary phosphate

is absorbed.
• The absorption is stimulated by both PTH and
Vit. D3.
• The Ca:P ratio in diet affects the absorption and
excretion of phosphorus.
• If one is in excess in diet, the excretion of the other
is increased.
Cont..
•Regulation: Regulation of Ca and P is under the similar
control mechanisms by kidney with respect to PTH and
vit. D.
•Role of Kidneys
• Phosphate uptake is sodium dependent, about 85 percent of
filtered PO4 is reabsorbed by the proximal tubules.
•Phosphate reabsorption is increased when dietary intake is
reduced by a PTH-dependent mechanism.
Cont.…

• Plasma inorganic phosphate is a major regulator of

25-OH-D3.
• Increase of↑ 1,25 (OH)2 D3 activity increases↑ PO4
absorption.
• Decrease ↓ of 1,25 (OH)2D3 decrease ↓ PO4
absorption
Cont.…

•FUNCTIONS
•Phosphate is the constituent of bone and teeth.
•Energy transfer: The free energy produced by
metabolic reactions may be stored as high energy
phosphate ATP, creatine phosphate.
•Acid-base balance: The buffer which is effectively handled by kidneys is a phosphate buffer.
•It is a mixture of dibasic and monobasic phosphates.
•Phosphorylation/dephosphorylation and phosphorolysis reaction involves phosphate.
•Enzyme action: Phosphate of several coenzymes such as NADP, TPP, is involved in
enzymatic reactions.
•Constituent of phospholipids, nucleotides/nucleic acids, lipoproteins, phosphoproteins is
phosphate
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