Calcium and Phosphate Homeosatsis

7/31/2019 Calcium and Phosphate Homeosatsis

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Dr. Niranjan Murthy H L

Associate Professor

Dept of Physiology

SSMC, Tumkur


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Tetany

Increased excitability of the nerves

Hypocalcemia (35% of normal)

Trousseau sign

Chvostek sign


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Hypercalcemia

Depression of nervous system

Sluggish reflexes

Constipation & lack of appetite Precipitation of calcium phosphate crystals

(>17mg/dL)


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Calcium

Functions:

Hemostasis- blood clotting

Excitability

Muscle contraction

Second messenger

Bone & teeth formation

Milk production

Release of neurotransmitters


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Calcium

Distribution:


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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


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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


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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)


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Relationship between calcium and

phosphate

Hydroxyapatite crystals

[Ca2+

] X [PO4-

]>solubility product= Bonedeposition

[Ca2+

] X [PO4-

]


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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


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Hydroxyapatite crystals

400nm long, 100nm wide, 10-30nm thick

Ca/P ratio=1.7/1

Supersaturated state of Ca2+ and PO4-

Inhibitors of crystallization


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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


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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


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Regulation of serum calcium

Depends on intestinal absorption, renalexcretion and bone remodeling

(1000


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Regulation of serum calcium Depends on 3 hormones- Parathormone,

Vitamin D, Calcitonin


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Parathormone

Chief cells ofparathyroid glands

Peptide hormone;

84 amino acids

Hypercalcemic hormone

Half life 10mins

Cleaved in liver Excreted from kidneys


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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


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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


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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


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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


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Synthesis of calcitriol


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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]


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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-


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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


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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


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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


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3. Renal tissue:

Loss of Na

+

, Ca

2+

and PO42-

Inhibits 1hydroxylase


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Clinical correlates

Hypoparathyroidism

Removal of parathyroids

Signs of hypocalcemic tetany

Low plasma calcium and increased phosphate

Treated with vit D3

Occasionally PTH is used


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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


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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


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Osteoporosis

Result of diminished organic bone matrix

Causes: lack of physical activity, menopause,

old age, malnutrition, vit C deficiency,

cushings syndrome


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Physiology of teeth


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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


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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

Calcium and Phosphate Homeosatsis

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