CALCIUM

Sources and RDA

OBJECTIVES
Metabolism of calcium

Functions of calcium

Hormonal Regulation of plasma calcium

Disorders of calcium metabolism

 CALCIUM

Calcium is the most abundant mineral in the body

Human body contain about 1-1.5 kg of

calcium
DAILY REQUIREMENTS OF CALCIUM

Children Adults Pregnancy

1000mg/day 500mg/day and
lactation
1500mg/day
 METABOLISM OF CALCIUM

Factors
Mechanism of
Absorption affecting
absorption
absorption

Excretion of Distribution
calcium and storage
METABOLISM OF CALCIUM - ABSORPTION

Upper
Site small
intestine

20-35% of
Efficiency
dietary Ca
 Absorption and excretion
• Usual intakes is 1000 mg/day
• About 35 % is absorbed (350 mg/day) by the
intestines
• Calcium remaining in the intestine is excreted in
the feces
• 250 mg/day enters intestine via secreted
gastrointestinal juices and sloughed mucosal cells
• 60-70 % of the daily intake is excreted in the feces
• 10 % of the ingested calcium is excreted in the
urine
• Calcium must be in a soluble and ionized form
before it can be absorbed
 FACTORS AFFECTING CALCIUM
ABSORPTION

Calcium absorption is increased by

Calcitriol Absorption is decreased by

PTH Alkaline pH
High protein diet Phytates and oxalates
Optimum Ca:P ratio Steatorrhea
Acidic pH Vitamin D deficiency
Bile salts Excess phosphate in diet
 Factors causing increased
absorption

• Vitamin D:
• Calcitriol induces the synthesis of carrier
protein (Calbindin) in the intestinal epithelial
cells & facilitates the absorption of calcium
• Parathyroid hormone:
• It increases calcium transport from the
intestinal cells by enhancing 1α-hydroxylase
activity
• Acidity:
• Favors calcium absorption because the Ca-salts,
particularly PO4 & carbonates are quite soluble in
acidic solutions
• In alkaline medium, the absorption of calcium is
lowered due to the formation of insoluble tricalcium
PO4
• High protein diet:
• A high protein diet favors calcium absorption
• If the protein content is low, only 5% may be absorbed
• Amino acids:
• Lysine & arginine increases calcium absorption
• Amino acids increase the solubility of Ca-salts &
thus its absorption
• Sugars and organic acids:
• Organic acids produced by microbial
fermentation of sugars in the gut, increases the
solubility of Ca-salts & increases their absorption
• Citric acid may also increase the absorption of
calcium
 Factors causing decreased absorption

• Phytic acid: Cereals contain phytic

acid (Inositol hexaphosphate) forms

insoluble Ca-salts & decreases the

absorption
• Oxalates: Present in some leafy

vegetables, causes formation of

• Malabsorption syndromes:

• Causing formation of insoluble calcium salt of

fatty acid
• Glucocorticoids:
• Diminishes intestinal transport of calcium
• Phosphate:
• High phosphate content will cause precipitation
as calcium phosphate
• Magnesium: High content of Mg decreases the
absorption
• Ca: P Ratio: 2:1
MECHANISM
OF CALCIUM
ABSORPTION

Calcium
absorption occurs
by 1,25(OH)2D3
mediated
mechanism.
• Calcitriol increases the intestinal absorption of
calcium and phosphate
• In the intestinal cells, calcitriol binds with a
cytosolic receptor to form a calcitriol-receptor
complex
• This complex interacts with a specific DNA leading
to the synthesis of a specific calcium binding
protein
• This protein increases calcium uptake by intestine
• The mechanism of action of calcitriol is similar to
that of steroid hormone
 Biochemical functions

• Development of bones and teeth:

• Bone is regarded as a mineralized connective
tissue
• Bones also act as reservoir for calcium
• The bulk quantity of calcium is used for bone and
teeth formation
• Osteoblasts induce bone deposition and osteoclasts
produce demineralization
 FUNCTIONS OF CALCIUM

Formation of Nerve Muscle Activation

bone and teeth conduction contraction of enzymes

Secretion of As a second Action on

Blood coagulation
hormones messenger myocardium
 EXCRETION OF CALCIUM

Stools Urine Sweat

Unabsorbed
calcium in 50-200mg/
the diet 15mg/day
day
60 – 70%
DISTRIBUTION AND STORAGE OF CALCIUM

99% present in
Human body bone and teeth
contain
about 1-1.5 1% in soft tissue
kg of calcium and extracellular
fluid

Plasma calcium : 9-11mg/dl

REGULATION OF ENZYME ACTIVITY

Ca++ activates Ca++ Inhibits

• Glycogen • Pyruvate kinase
phosphorylase • Trypsin
kinase
• Amylase
REGULATION OF PLASMA CALCIUM
%

10%

Free or ionized calcium

Protein bound
complex with anions
50%
40%
REGULATION OF PLASMA CALCIUM

Calcitriol Gut

3 3
Hormones
PTH Bone
Organs
Calcitonin Kidney
 Vitamin D promotes intestinal
calcium absorption
• Vitamin D acts via steroid hormone like
receptor to increase transcriptional and
translational activity
• One gene product is calcium-binding protein
(CaBP)
• CaBP facilitates calcium uptake by intestinal
cells
 Parathyroid Hormone
• PTH is synthesized and secreted by the
parathyroid gland which lie posterior to the
thyroid glands.

• The blood supply to the parathyroid glands is

from the thyroid arteries.

• The Chief Cells in the parathyroid gland are the

principal site of PTH synthesis.
 Regulation of PTH
• The dominant regulator of PTH is plasma
calcium.
• Secretion of PTH is inversely related to
calcium.
• Maximum secretion of PTH occurs at plasma
Ca2+ below 3.5 mg/dL.
• At Ca2+ above 5.5 mg/dL, PTH secretion is
maximally inhibited.
 PTH action
• The overall action of PTH is to increase plasma Ca++
levels and decrease plasma phosphate levels.
• PTH acts on the bones to stimulate Ca++ resorption
• In kidney PTH stimulates Ca++ reabsorption in the distal
tubule of the kidney and to inhibit reabsorption of
phosphate (thereby stimulating its excretion).
• In kidney PTH stimulates 1,α-hydroxylase enzyme which
results in increased synthesis of 1,25,dihydroxy
cholicalciferol
• PTH also acts indirectly on intestine by stimulating 1,25-
(OH)2-D synthesis.
 Calcitonin
• Calcitonin acts to decrease plasma Ca++ levels.
• While PTH and vitamin D act to increase plasma
Ca++ only calcitonin causes a decrease in plasma
Ca++.
• Calcitonin is synthesized and secreted by the
parafollicular cells of the thyroid gland.
• They are distinct from thyroid follicular cells by
their large size, pale cytoplasm, and small
secretory granules
 Calcitonin
• The target cell for calcitonin is the osteoclast.
• Calcitonin acts via increased cAMP concentrations
to inhibit osteoclast motility and inactivates them.
• The major effect of calcitonin administration is a
rapid fall in Ca2+ caused by inhibition of bone
resorption
• Calcinotonin also inhibits the enzyme 1-α
hydroxylase thus decreasing the synthesis of
calcitriol and calcium absorption
DISORDERS OF CALCIUM METABOLISM

Hypocalcemia
Hypercalcemia
 HYPOCALCEMIA

Feature
Causes
s
 HYPOCALCEMIA
CAUSE Inadequate intake
S
Impaired absorption
Increased excretion
Magnesium deficiency
Acute pancreatitis
 Causes of hypocalcaemia
1) Increased Phosphate levels
– Chronic kidney disease
– Phosphate therapy

2) Hypoparathyroidism
– Post thyroidectomy hypocalcaemia
– Congenital deficiency (Di George Syndrome)
– Idiopathic hypoparathyroidism
– Severe hypomagnesaemia

3) Vitamin D deficiency
– Osteomalacia/rickets
– Vitamin D resistance
• Hypoparathyroidism associated with other
diseases states:
- Addison’s disease
- Pernicious Anemia
-Fungal disease like candidiasis
• Other causes:
– Acute pancreatitis
– Citrate blood in massive transfusion
– Low plasma albumin eg. Malnutrition, Chronic liver
disease
– Malabsorption eg. Coeliac disease
– Osteomalacia & Rickets
– Magnesium Defeciency
 HYPOCALCEMIA - FEATURES

Muscle cramps Cardiac

Cataract
and tetany arrhythmias

Laryngospasm
Prolongation Chronic
of QT interval hypocalcemia
Convulsion
 HYPOCALCEMIA – SIGNS OF TETANY

Chvostek’s
Contraction of facial muscle in
sign response to tapping the facial nerve

Carpal spasm occurring after occlusion

Trousseau’s
of the brachial artery with BP cuff for
sign 3 min
HYPERCALCEMIA

Causes

Features
• Hypercalcaemia:-when the serum calcium level
exceeds 11.0mg/dl it is called as hypercalcaemia
(normal serum calcium level is 9 to 11mg/dl).
 HYPERCALCEMIA

CAUSE Increased intake

S
Increased absorption
Decreased excretion
Malignancy
 Hyperparathyroidism: causes
Primary Hyperparathyroidism
– Solitary Adenomas (85%)
– Multiple Adenomas(2%)
– Parathyroid Carcinoma (<1% cases)
– Familial benign hyperplasia of chief cells (FBH)
Secondary Hyperparathyroidism
– Renal failure
– Vitamin D deficiency
 Malignant hypercalcemia: major causes

• PTHrP – mediated
Parathyroid hormone-related protein (or PTHrP) is a protein
member of the parathyroid hormone family. It is occasionally
secreted by cancer cells
--Breast carcinoma
– Squamous carcinoma (lung, head & neck, esophagus)
– Renal carcinoma
• Cytokine - mediated
– Myeloma (lymphoma, leukemia)
• Endocrine causes:
Hyperthyroidisim, Acromegaly
• Granulomatous diseases:
Tuberculosis, sarcoidosis
• Over Dosage of Vitamins:
Hypervitaminosis D
• Drug-induced Hypercalcaemia:
Thiazide diuretics, spironlactone
 HYPERCALCEMIA - FEATURES
FEATURE
S
Metastatic calcification
Neurological symptoms
Renal symptoms
Gastrointestinal symptoms
Cardiac arrhythmias