of 35
7/31/2019 Calcium and Phosphate Homeosatsis
1/35
Dr. Niranjan Murthy H L
Associate Professor
Dept of Physiology
SSMC, Tumkur
7/31/2019 Calcium and Phosphate Homeosatsis
2/35
Tetany
Increased excitability of the nerves
Hypocalcemia (35% of normal)
Trousseau sign
Chvostek sign
7/31/2019 Calcium and Phosphate Homeosatsis
3/35
Hypercalcemia
Depression of nervous system
Sluggish reflexes
Constipation & lack of appetite Precipitation of calcium phosphate crystals
(>17mg/dL)
7/31/2019 Calcium and Phosphate Homeosatsis
4/35
Calcium
Functions:
Hemostasis- blood clotting
Excitability
Muscle contraction
Second messenger
Bone & teeth formation
Milk production
Release of neurotransmitters
7/31/2019 Calcium and Phosphate Homeosatsis
5/35
Calcium
Distribution:
7/31/2019 Calcium and Phosphate Homeosatsis
6/35
Calcium Distribution
1000gm of Ca2+ in bones of 70kg man
Plasma Calcium:
45% bound to albumin 10% complexed with citrate ion, HPO4
2- and
HCO3-
45% ionic form Ionic Ca2+ 10mg/dL or 2.5 mmol/L or 5 meq/L
7/31/2019 Calcium and Phosphate Homeosatsis
7/35
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
7/31/2019 Calcium and Phosphate Homeosatsis
8/35
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)
7/31/2019 Calcium and Phosphate Homeosatsis
9/35
Relationship between calcium and
phosphate
Hydroxyapatite crystals
[Ca2+
] X [PO4-
]>solubility product= Bonedeposition
[Ca2+
] X [PO4-
]
7/31/2019 Calcium and Phosphate Homeosatsis
10/35
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
7/31/2019 Calcium and Phosphate Homeosatsis
11/35
7/31/2019 Calcium and Phosphate Homeosatsis
12/35
Hydroxyapatite crystals
400nm long, 100nm wide, 10-30nm thick
Ca/P ratio=1.7/1
Supersaturated state of Ca2+ and PO4-
Inhibitors of crystallization
7/31/2019 Calcium and Phosphate Homeosatsis
13/35
Bone formation and resorption Osteoblasts- modified fibroblasts- secretion of
type I collagen Osteoclasts- modified monocytes- RANK
Ligand
Osteocytes- bone cells- provide rapid andtransient movement of calcium from bone toECF
7/31/2019 Calcium and Phosphate Homeosatsis
14/35
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
7/31/2019 Calcium and Phosphate Homeosatsis
15/35
Regulation of serum calcium
Depends on intestinal absorption, renalexcretion and bone remodeling
(1000
7/31/2019 Calcium and Phosphate Homeosatsis
16/35
Regulation of serum calcium Depends on 3 hormones- Parathormone,
Vitamin D, Calcitonin
7/31/2019 Calcium and Phosphate Homeosatsis
17/35
Parathormone
Chief cells ofparathyroid glands
Peptide hormone;
84 amino acids
Hypercalcemic hormone
Half life 10mins
Cleaved in liver Excreted from kidneys
7/31/2019 Calcium and Phosphate Homeosatsis
18/35
Physiologic Actions
Osseous tissue:
1. Bone resorption and mobilization of calcium
2. Bone remodeling in long term by stimulatingboth osteoblasts and osteoclasts
Intestinal tissue:
1. Calcium and phosphate absorption2. Acts synergistically with vit D
7/31/2019 Calcium and Phosphate Homeosatsis
19/35
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
7/31/2019 Calcium and Phosphate Homeosatsis
20/35
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
7/31/2019 Calcium and Phosphate Homeosatsis
21/35
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
7/31/2019 Calcium and Phosphate Homeosatsis
22/35
Synthesis of calcitriol
7/31/2019 Calcium and Phosphate Homeosatsis
23/35
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]
7/31/2019 Calcium and Phosphate Homeosatsis
24/35
2. Intestinal tissue:
Increase Ca2+ absorption by increasingcalbindin proteins and Ca2+H+ ATPase pumps
Increased phosphate absorption
3. Renal tissue:
Promotes distal tubular reabsorption of Ca2+
Promotes proximal tubular reabsorption of
PO42-
7/31/2019 Calcium and Phosphate Homeosatsis
25/35
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
7/31/2019 Calcium and Phosphate Homeosatsis
26/35
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
7/31/2019 Calcium and Phosphate Homeosatsis
27/35
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
7/31/2019 Calcium and Phosphate Homeosatsis
28/35
3. Renal tissue:
Loss of Na
+
, Ca
2+
and PO42-
Inhibits 1hydroxylase
7/31/2019 Calcium and Phosphate Homeosatsis
29/35
Clinical correlates
Hypoparathyroidism
Removal of parathyroids
Signs of hypocalcemic tetany
Low plasma calcium and increased phosphate
Treated with vit D3
Occasionally PTH is used
7/31/2019 Calcium and Phosphate Homeosatsis
30/35
Hyperparathyroidism
Primary and secondary
Parathyroid secreting tumors
Chronic renal disease and rickets Hypercalcemia and hypophosphatemia
Osteitis fibrosa cystica
Muscle weakness, constipation, lack ofappetite
Renal calculi
Parathyroid poisoning
7/31/2019 Calcium and Phosphate Homeosatsis
31/35
Vitamin D deficiency
Rickets in children
Osteomalacia in adults
In children- weakness and bowing of weight
bearing bones, dental defects andhypocalcemia
Vitamin D resistant rickets
7/31/2019 Calcium and Phosphate Homeosatsis
32/35
Osteoporosis
Result of diminished organic bone matrix
Causes: lack of physical activity, menopause,
old age, malnutrition, vit C deficiency,
cushings syndrome
7/31/2019 Calcium and Phosphate Homeosatsis
33/35
Physiology of teeth
7/31/2019 Calcium and Phosphate Homeosatsis
34/35
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
7/31/2019 Calcium and Phosphate Homeosatsis
35/35
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