Calcium/Phosphate/Magnesium

BONE METABOLISM
Requirements for growth of bone
1. Calcium
2. Phosphorus
3. Magnesium
4. Collagen
5. Vitamin D
6. Parathyroid hormone
7. Calcitonin
8. Sex steroids
9. Vitamin C
10. Vitamin K
11. Vitamin A
12. Other proteins/enzymes
Bone mineralization

Process of deposition of calcium and phosphate on the organic matrix, osteoid synthesized and
secreted by osteoblasts under the effect of PTH and calcitriol.

Vitamin D induced secretion of alkaline phosphatase by osteoblasts liberates phosphates.

The ionic concentration of [calcium × phosphate] reaches supersaturation. Calcium phosphate is

deposited as hydroxyapatite over the matrix of triple stranded quarter staggered collagen.
 Class assignment
Response to Low serum
Calcium ????
 Calcium Phosphate Magnesium
Total amount- 1Kg Total amount- 500 g Total amount- 25g
Bone- 99% Bone- 85% Bone- 50%
Soft Tissue-1% Soft Tissue-15% Soft Tissue-50%
Blood level – 8.5-10.5 mg/dl Blood level – 4.5-5.5 mg/dl Blood level – 1.5-2.5 mg/dl
Free ionic- 50% Free ionic- 55% Free ionic- 55%
Protein bound-45% Protein bound-15% Protein bound-30%
Salt form-5% Salt form-30% Salt form-15%
Daily requirement-800 mg Daily requirement-800 mg Daily requirement-250-350 mg
Excretion Excretion Excretion
Fecal- 300 mg/d Fecal- 200 mg/d Fecal- 100 mg/d
Urinary- 200mg/d Urinary- 100mg/d Urinary- 50mg/d
Absorption Absorption Absorption
Duodenum/jejunum Small intestine Jejunum/ileum
70% active transcellular 90% active Na-Phosphate 70% active
(Vitamin D controlled) co-transport (Vitamin D controlled)
Passive paracellular (unregulated) (Vitamin D controlled)
 Calcium
Milk is a good source; contains about 100 mg/dl. Serum Calcium Levels :
8.6 mg/dL-10.4 mg/dL
Egg, fish and vegetables are medium sources.
Adult needs 800 mg / day.
Cereals contain only small amount of calcium. Child needs 1200 mg/ day.
During pregnancy and lactation
1500 mg/day
For prevention of osteoporosis:
Calcium (1500 mg/day) & vitamin D (20 μg/day).
Factors Causing Increased Absorption
Vitamin D: Calcitriol facilitates the absorption of calcium.
Gastric Acidity: Favours the calcium absorption.
Amino acids: Lysine & arginine increase the calcium absorption.

Factors Causing Decreased Absorption

Phytic acid: Hexaphosphate of inositol is present in cereals.
Oxalates: In leafy vegetables, cause formation of insoluble calcium oxalates.
Malabsorption syndromes: Unabsorbed fatty acid form insoluble salt.
Phosphate: High phosphate cause precipitation as calcium phosphate.
 • Calcium is mainly
extracellular; membrane is
impermeable to Ca++.

• Calcium enters cell by rapid,

but low affinity Na+/Ca++
exchange mechanism.

• Entry of Ca++ into

mitochondria is by a calcium
uniport system.
Ca
uniport
• Other calcium channels are
voltage operated and second
messenger operated.

VC: voltage operated channels, activated by membrane depolarization; SOC: second messenger operated channels,
activated by inositol phosphate, cyclic nucleotides or diacylglycerol; HRC: hormone receptor operated channels, activated
by hormones or neurotransmitters; Na-Ca Ex: sodium-calcium exchanger.
 FUNCTIONS
Bone and Teeth: The bulk quantity is used for bone and teeth formation.
Nerve Conduction: Necessary for transmission of nerve impulses.
Muscle contraction: Activates ATPase for actin-myosin coupling and interaction with troponin C.
Myocardium: Contraction by cardiac node activation. Ca++ prolongs systole.
Coagulation: Calcium has most vital role as factor IV in blood coagulation cascade.
Vascular Permeability: Decreases the passage of serum through capillaries.
Secretion of Hormones: Required for secretion of insulin, parathyroid hormone, calcitonin etc.
Second Messenger: Second messengers of different hormones like glucagon.
Activation of Enzymes: Calmodulin bind with Ca++ for activation of various regulatory kinases.
Folding of Proteins: Helps in molten globule stabilization for proper folding of proteins
Causes of hypercalcemia Causes of hypocalcaemia
1. Hyperparathyroidism/high vitamin D 1. Deficiency of vitamin D
2. Bone demineralization Low sunlight exposure/ Malabsorption /malnutrition
 Multiple myeloma /Hepatic diseases//Nephrotic syndrome (decreased
 Paget’s disease synthesis/binding protein lost)
 Metastatic carcinoma of bone 2. Deficiency of parathyroid
3. Calcium excess in circulation Hypoparathyroidism
Dehydration/ acidosis 3. Deficiency of calcium
Malabsorption/ Pancreatitis/ low reabsorption due to
renal disease
4. Increase in phosphorus level
Renal failure/Phosphate infusion/Renal tubular acidosis
Symptoms of hypercalcemia Symptoms of hypocalcaemia
1. Polyuria and polydipsia (ADH antagonism) 1. Muscle cramps
2. Confusion, depression, psychosis 2. Paraesthesia, especially in fingers
3. Osteoporosis and pathological fracture 3. Neuromuscular irritability, muscle
twitching
4. Renal stones
4. Tetany
5. Ectopic calcification myositis & pancreatitis
5. Seizures
6. Cardiac arrest in systole
6. Bradycardia
7. Prolonged QT interval
Phosphorus
Total body phosphate is about 500g;
85% is in bone and teeth and 15% in muscles.
Phosphate is mainly an intracellular ion.

Requirement and Source

Requirement is about 800 mg/day. Serum phosphate is 2.5–4.5 mg/dL in adults
In children 5–6 mg/dL.
Milk is a good source.
The postprandial decrease of phosphorus is
Cereals, nuts and meat are moderate sources. due to the utilization of phosphate for
metabolism.
Calcitriol increases phosphate absorption.
Functions of phosphate
1. Formation of bone and teeth
2. Production of high energy phosphate compounds such as ATP, CTP, GTP
3. Synthesis of nucleoside coenzymes such as NAD and NADP
4. DNA and RNA synthesis, (phosphodiester linkages)
5. Formation of phosphate esters, such as glucose-6-phosphate
6. Formation of phosphoproteins, e.g. casein
7. Formation of phospholipids, e.g. lecithin
8. Activation of enzymes by phosphorylation
9. Signalling messenger like cAMP/cGMP
10.Phosphate provides buffer system in blood/urine.
Causes of hyperphosphatemia Causes of hypophosphatemia
1. Increased absorption of phosphate 1. Decreased absorption of phosphate
Excess vitamin D/Phosphate infusion Malnutrition/Malabsorption/Chronic diarrhoea/
Vitamin D deficiency
2. Increased cell lysis
Chemotherapy for cancer/Bone secondaries 2. Intracellular shift
Crush Injury/ Rhabdomyolysis Insulin therapy
3. Decreased excretion 3. Increased excretion / decreased reabsorption
Renal impairment/Hypoparathyroidism Hyperparathyroidism/Fanconi’s syndrome/
Hypophosphatemic rickets
4. Hypomagnesemia
PTH mediated / Renal reabsorption mediated
5. Drugs
Antacids [Al(OH)3], Salicylate
Magnesium
Functions of Magnesium

1. Formation of bone and teeth

2. Neuronal stability

3. Stabilization of ATP in kinase /ATPase as a co-factor

4. DNA & RNA synthesis (Divalent cation for polymerization)

Source:
Green leafy vegetables/ nuts
Meat of herbivorous animals
 Causes of Hypomagnesemia Causes of Hypermagnesemia

I. Excessive magnesium intake

I. Impaired intestinal absorption
Malabsorption syndromes/ Vitamin D deficiency Parenteral magnesium administration

II. Increased intestinal losses II. Rapid mobilization from soft tissues
Protracted vomiting/diarrhea
Trauma
III. Impaired renal tubular reabsorption
Shock
Genetic
Tubulointerstitial disease/ Post-obstruction Acute Tubular Necrosis (diuretic Sepsis
phase)
Cardiac arrest
Drugs like Ethanol, Diuretics (loop, thiazide, osmotic)
Diabetes mellitus, Hypercalcemia, Phosphate depletion III. Impaired magnesium excretion

IV. Rapid shifts from extracellular fluid Genetic/Familial

Recovery from diabetic ketoacidosis, Correction of respiratory acidosis
Renal failure
Treatment of vitamin D deficiency, Osteoblastic metastases
Burns, Excessive sweating
Thanks
 Class exercise

1? 2?

3?
 Class exercise
Q. 4-11: state either increase or Q. 12-14: state either inhibits
decrease? or promotes?
14

13
4 5 6 9 10
8

12
7 11
Answer