Dr.

Niranjan Murthy H L Associate Professor Dept of Physiology SSMC, Tumkur

Tetany
Increased excitability of the nerves Hypocalcemia (35% of normal) Trousseau sign Chvostek sign

Hypercalcemia
Depression of nervous system Sluggish reflexes Constipation & lack of appetite Precipitation of calcium phosphate crystals (>17mg/dL)

Calcium
Functions: Hemostasis- blood clotting Excitability Muscle contraction Second messenger Bone & teeth formation Milk production Release of neurotransmitters

Calcium
Distribution:

Calcium Distribution
1000gm of Ca2+ in bones of 70kg man Plasma Calcium: 45% bound to albumin 10% complexed with citrate ion, HPO42- and HCO3 45% ionic form Ionic Ca2+ 10mg/dL or 2.5 mmol/L or 5 meq/L

Phosphate
Functions: Found in vital molecules like ATP, ADP, cAMP, 2,3 DPG, etc Role in regulating enzyme activity Role in acid-base balance Role in regulating plasma Ca2+ levels Integral part of nucleic acids

Phosphate
Distribution: Total body phosphorus: 500-800gm Bone phosphorus: 85-90% of total Total plasma phosphorus: 12mg/dL- 2/3rd as organic compounds and 1/3rd as inorganic form (Pi)

Relationship between calcium and phosphate

Hydroxyapatite crystals [Ca2+] X [PO4-]>solubility product= Bone deposition [Ca2+] X [PO4-]<solubility product= Bone resorption

Bone chemistry
Compact and trabecular bone 3 cells- osteoblast, osteocyte, osteoclast 3 hormones- parathormone, vitamin D, calcitonin 90% collagen 10% ground substance- hyaluronic acid & chondroitin sulphate Hydroxyapatite- Ca10(PO4)6(OH)2

Hydroxyapatite crystals
400nm long, 100nm wide, 10-30nm thick Ca/P ratio=1.7/1 Supersaturated state of Ca2+ and PO4-

Inhibitors of crystallization

Bone formation and resorption

Osteoblasts- modified fibroblasts- secretion of type I collagen Osteoclasts- modified monocytes- RANK Ligand Osteocytes- bone cells- provide rapid and transient movement of calcium from bone to ECF

 Exchangeable calcium salts in bone :0.4 to 1% of total bone calcium Continuous remodeling of bones 5% of bone mass remodeled at any given time 4% renewal of compact bone and 20% renewal of cancellous bone per year Related to stress

Regulation of serum calcium

Depends on intestinal absorption, renal excretion and bone remodeling
(1000

 Depends on 3 hormones- Parathormone, Vitamin D, Calcitonin

Regulation of serum calcium

Parathormone
Chief cells of parathyroid glands Peptide hormone; 84 amino acids Hypercalcemic hormone Half life 10mins Cleaved in liver Excreted from kidneys

Physiologic Actions
Osseous tissue: 1. Bone resorption and mobilization of calcium 2. Bone remodeling in long term by stimulating both osteoblasts and osteoclasts Intestinal tissue: 1. Calcium and phosphate absorption 2. Acts synergistically with vit D

 Renal tissue: 1. Promote active reabsorption in distal nephron 2. Inhibits phosphate reabsorption 3. Stimulate 1,25 (OH)cholecalciferol Overall: Hypercalcemia Hypophosphatemia Hyperphosphaturia Hypocalciuria followed by hypercalciuria

 Mechanism of action: 3 receptors; G protein coupled Regulation of PTH secretion: (i) Plasma calcium- calcium receptor (ii) 1,25 (OH)cholecalciferol (iii) Increased plasma phosphate (iv) Magnesium

Vitamin D3
Secosteroids Skin, liver and kidney 25(OH) cholecalciferol, 1,25(OH)2 cholecalciferol [calcitriol] Transported in plasma in combination with vit D binding protein

Synthesis of calcitriol

Actions of Vit D3
Calbindin D 9k and 28k in intestine, kidneys, brain, etc 1. Osseous tissue: Together with PTH, increases mobilization of Ca2+ and PO42- from bone Bone deposition by raised plasma Ca2+ and PO42- [Antirachitic effect]

2. Intestinal tissue: Increase Ca2+ absorption by increasing calbindin proteins and Ca2+H+ ATPase pumps Increased phosphate absorption 3. Renal tissue: Promotes distal tubular reabsorption of Ca2+ Promotes proximal tubular reabsorption of PO42-

Regulation of Vit D synthesis

Renal formation of 1, 25 (OH)2 cholecalciferol under the influence of 1 hydroxylase is regulated by Ca2+ and PO43- and PTH Prolactin stimulates 1, 25 (OH)2 cholecalciferol production Estrogen increases total circulating 1, 25 (OH) 2 cholecalciferol Hyperthyroidism is associated with decreased circulating 1,25 (OH) 2 cholecalciferol GH, calcitonin and hCS increase 1,25 (OH) 2 cholecalciferol

Calcitonin
Hypocalcemic hormone Parafollicular C cells 32 amino acids Stimulated by Ca2+, gastrin, CCK, estrogens, dopamine, alpha adrenergic agonists, secretin Half life less than 10 mins

Actions of calcitonin
1. Osseous tissue: Inhibits osteolytic activity of osteclasts and osteocytes Decrease in calcium levels and increase in alkaline phosphatase 2. Intestinal tissue: Inhibits absorption of Ca2+ and PO42 Inhibits gastric motility & gastric secretion

3. Renal tissue: Loss of Na +, Ca2+ and PO42Inhibits 1 hydroxylase

Clinical correlates Hypoparathyroidism

Removal of parathyroids Signs of hypocalcemic tetany Low plasma calcium and increased phosphate Treated with vit D3

Occasionally PTH is used

Hyperparathyroidism
Primary and secondary Parathyroid secreting tumors Chronic renal disease and rickets Hypercalcemia and hypophosphatemia Osteitis fibrosa cystica Muscle weakness, constipation, lack of appetite Renal calculi Parathyroid poisoning

Vitamin D deficiency
Rickets in children Osteomalacia in adults In children- weakness and bowing of weight bearing bones, dental defects and hypocalcemia Vitamin D resistant rickets

Osteoporosis
Result of diminished organic bone matrix Causes: lack of physical activity, menopause, old age, malnutrition, vit C deficiency, cushings syndrome

Physiology of teeth

Enamel; Protein fiber meshwork resistant to acids, enzymes and corrosives Hydroxyapatite crystals and other minerals Dentin: Collagen and hydroxyapatite crystals Nourished by inner odontoblasts Cementum: Secreted by periodontal membrane Pulp: Lymphatics, nerves and blood vessels

 Deposition and reabsorption of calcium from dentin and cementum Caries: Plaque, streptococcus mutans, acids & proteolytic enzymes Fluorine replaces hydroxyl ions in hydroxyapatite crystals and make them less soluble