CALCIUM METABOLISM

Presenter: Dr. Ramin Maharjan

1st year resident
Department of
Orthopaedics
PAHS
Moderator: Dr Sagun Basnyat
 CONTENTS
Role of Calcium

Distribution of calcium in the human body

Measurement of serum calcium

Dietary requirements

Calcium absorption and excretion

Regulation of serum calcium levels

Hypocalcemia and Hypercalcemia

Disorders
 Role of calcium

Vital role in physiological and biochemical

processes of organisms and cells:
• In signal transduction, as second messenger
• In neurotransmitter release from neurons
• In muscle contraction
• In blood coagulation
• In protein synthesis
• In bone formation
 DISTRIBUTION OF CALCIUM IN THE
HUMAN BODY

Calcium • 0.1% in extracellular fluid

constitutes • 1% in cells
2% of body • More than 99% stored in
weight- bones
approx. 1.2 kg.
DISTRIBUTION OF CALCIUM IN THE
HUMAN BODY
Distribution of Serum Calcium

Ionized (or free)

15% calcium

45%
Calcium bound to
albumin
40%

Calcium complexed
with citrate, sulfate, or
phosphate
 SERUM CALCIUM MEASUREMENTS

Normal serum calcium concentration is 8.6-10.3 mg/dL (2.15-

2.54 mmol/L).

Normal ionized calcium concentration is 4.4-5.2 mg/dL.

Measurement of ionized calcium is the gold standard for

assessing calcium status.
 SERUM CALCIUM MEASUREMENTS

Conditions in which total Conditions in which ionized

calcium can change without calcium can change without
affecting ionized calcium: affecting total calcium:
• Hypoalbuminemia • Acid-base disorders
(decreased total calcium) (increased pH leads to
• Corrected Ca = Measured decreased ionized calcium)
Ca + 0.8 X (4-Albumin) • Hyperphosphatemia
• Hyperalbuminemia (decreased ionized calcium)
(increased total calcium) • Hyperparathyroidism
• Multiple myeloma (increased ionized calcium)
(increased total calcium)
 DIETARY REQUIREMENTS

Approx. 600 mg/day for children.

Approx. 1300 mg/day for ages 10-25 years.

750 mg/day for adults 25-50 years.

1200-1500 mg/day for adults >50 years.

1500 mg/day for pregnant women.

2000 mg/day for lactating women.

1500 mg/day for postmenopausal women and patients with healing fracture of long bone.
 Source of Calcium
• dairy products; milk, yogurt, and cheese
• Vegetables, grains, legumes, fruit
Food •
•
meat, fish, eggs
Fortified foods - orange juice, other beverages,
and ready-to-eat cereals

Dietary • calcium carbonate and

• calcium citrate
supplements
 CALCIUM ABSORPTION AND EXCRETION
• Absorbed in the duodenum by active transport (transcellular pathway).
– Requires ATP and calcium binding protein
– Regulated by 1,25-(OH)2D3
• Absorbed in the jejunum by passive diffusion (paracellular pathway)
Mean urinary loss averages 22 percent and fecal loss 75 percent of total calcium
intake, with minor losses from sweat, skin, hair, etc
Absorption is inhibited by:

• Excessive intake of phosphates (in soft drinks)

• Oxalates (in tea and coffee)
• Fats
• Certain drugs such as corticosteroids
• Intestinal malabsorption disorders
Homeostatic regulation of calcium

3 organs • Bone, skin and kidney

3 hormones • PTH, Calcitonin, Vitamin D

Physiology of calcium and phosphate metabolism,

formation of bone, regulation of vitamin D, PTH and
calcitonin are closely intertwined.
REGULATION OF SERUM CALCIUM LEVELS

First line of defense - Buffer function of the exchangeable

calcium in bones

Second line of defense - Hormonal control of calcium ion

concentration
• Parathyroid hormone (PTH)
• Vitamin D
• Calcitonin
• FGF23
• Corticosteroids
• Thyroid hormone
• Estrogen
 BUFFER FUNCTION OF EXCHANGEABLE
CALCIUM IN BONES
Major crystalline salt is hydroxyapatite- Ca10(PO4)6(OH)2, but it does not precipitate in
extracellular fluid.

The exchangeable calcium salts in bone are amorphous calcium compounds, mainly CaHPO4
The quantity of these salts available for exchange is about 0.5 to 1% of total calcium salts of bone, a total
of 5 to 10 grams of calcium.
HORMONAL CONTROL OF CALCIUM ION
CONCENTRATION
PARATHYROID HORMONE
Vitamin D
metabolism
HORMONAL CONTROL OF CALCIUM ION
CONCENTRATION
 VITAMIN D

• Children (1 to 18 years)- 600 IU (15 mcg)

Recommended • Pregnant and lactating women- 600 IU
(15 mcg)
daily allowance • Adults (<70 years)- 600 IU (15 mcg)
• Adults (>70 years)- 800 IU (20 mcg)
(RDA):
 CORTICOSTEROIDS

Inhibit intestinal absorption of calcium when used chronically

in high doses by decreasing binding proteins.

Decreases bone formation (cancellous more than cortical) by

inhibition of collagen synthesis and osteoblast production.

Do not affect mineralization.

Alternate day therapy may reduce these effects.

 ESTROGEN
Prevents bone loss by inhibiting bone resorption.

Helpful in postmenopausal women if started within 5 to 10 years of

menopause.

Risk of endometrial cancer is reduced when combined with cyclic

progestin therapy.

May increase risk of heart disease and breast cancer.

Other postmenopausal pharmacologic interventions (alendronate,

raloxifene) should be strongly considered.
 THYROID HORMONE

Affects bone resorption more than bone formation.

Large (thyroid-suppressive) doses of thyroxine can lead

to osteoporosis.

Regulates skeletal growth at physis.

Stimulates chondrocyte growth, type X collagen

synthesis and alkaline phosphatase activity.
 GROWTH HORMONE

Increases gut absorption of calcium more than it

increases urinary excretion, leading to positive calcium
balance.

Insulin and somatomedins participate in this effect.

 Disorders in
Calcium Homeostasis

Hypocalcemia Hypercalcemia
Serum calcium <8.5 mg/dL. Serum calcium > 10.5 mg/dL
 HYPOCALCEMIA
• Causes:
– Vitamin D deficiency
– Chronic renal failure
– Hypoparathyroidism
– Hypomagnesemia
– Pancreatitis
– Drugs (denosumab, zoledronate)
 HYPOCALCEMIA
• Clinical features:
– Numbness, paresthesias
– Muscle spasms
– Convulsions
– Laryngeal spasm
– Hyperreflexia
– Chvostek sign
– Trousseau sign
• ECG changes: Prolonged QT interval
• Treatment:
– IV calcium gluconate for acute hypocalcemia
– Vitamin D and teriparatide for chronic hypocalcemia
 HYPERCALCEMIA
• Causes:
– Hyperparathyroidism
– Malignancy
– Granulomatous disorders (sarcoidosis,
tuberculosis, histoplasmosis)
– MEN I and II
– Familial hypocalciuric hypercalcemia
– Prolonged immobilization
– Drugs (lithium, thiazides)
 HYPERCALCEMIA

• Clinical features:
– Polyuria, polydipsia
– Kidney stones
– Confusion, stupor, weakness
– Constipation
– Anorexia, nausea, vomiting, muscle weakness
• ECG changes: Shortened QT interval
• Treatment:
– IV fluids
– IV bisphosphonates and glucocorticoids
– Treatment of underlying cause
 HYPOPARATHYROIDISM
• Low PTH levels with decreased serum calcium and increased
serum phosphate.
• Causes:
– Hypoparathyroidism most commonly follows thyroidectomy
– Autoimmune disease
– Magnesium deficiency
– DiGeorge syndrome
• Pseudohypoparathyroidism
– Rare genetic disorder caused by impaired peripheral sensitivity to PTH
– PTH normal or high
– Albright’s hereditary osteodystrophy (short stature, short 4th and 5th
metacarpals and mild mental retardation)
a. short 4th and 5th metacarpals
b. Knuckle, knuckle, dimple, dimple sign
 HYPERPARATHYROIDISM
• Increased PTH levels with increased serum calcium and
decreased serum phosphate.
• Types:
– Primary (usually due to an adenoma or hyperplasia).
– Secondary (due to persistent hypocalcemia leading to
parathyroid hyperplasia).
– Tertiary (when secondary hyperplasia leads to autonomous
overactivity).
• Treatment:
– Adequate hydration and decreased calcium intake
– Parathyroidectomy for primary hyperparathyroidism
 VITAMIN D DEFICIENCY
• Deficiency leads to osteomalacia in adults and
rickets in children.
• Decreased vitamin D, decreased serum calcium and
phosphate, increased PTH and ALP seen.
• Causes of vitamin D deficiency:
– Inadequate dietary intake
– Intestinal malabsorption
– Lack of sunlight exposure
– Impaired 25-hydroxylation in liver disease
– Impaired 1-alfa hydroxylation in renal disease
 OSTEOMALACIA
• Defective mineralization of osteoid due to deficiency of
vitamin D.
• Increased bone fragility and fracture risk.
• Clinical features:
– Bone pain
– Muscle weakness
– Waddling gait
• X-ray:
– Looser zone, a thin transverse band of rarefaction in an otherwise
normal-looking bone
– Vertebral fractures may show characteristic biconcave appearance
– Champagne glass pelvis
 RICKETS
• Defective mineralization of cartilagenous growth plate, causing
chondrocytes to pile up irregularly, increase in width of growth plate, poor
mineralization of the zone of calcification and sparse bone formation in
the zone of ossification.
• Clinical features:
– Tetany or convulsions
– Bow legs (genu varum)
– Bead-like costochondral junctions (rachitic rosary)
– Craniotabes (soft skull)
– Harrison’s sulcus (lateral indentation of the chest)
• X-ray:
– Epiphyseal widening and metaphyseal cupping/fraying
– Bowing of the diaphysis
 REFERENCES
• Miller’s Review of Orthopaedics, 8th edition
• Apley & Solomon’s System of Orthopaedics
and Trauma, 10th edition
• Guyton and Hall Textbook of Medical
Physiology, 12th edition
• UpToDate
• orthobullet
THANK YOU..!!