Hormonal regulation of calcium and phosphorus
homeostasis.
Calcium
• Regulate neuromuscular excitability
• Blood coagulation• Secretory processes• Membrane integrity• Plasma membrane transport• Enzyme reactions• Release of hormones and
neurotransmitters • Bone mineralization
Phosphorus
• Important role in cellular metabolism
• source of of energy in cellular reactions
• Component of phospholipids in membranes
Calcium Homeostasis
James T. McCarthy & Rajiv Kumar
Hormonal Regulators• Calcitonin (CT)
– Lowers Ca++ in the blood– Inhibits osteoclasts
• Parathormone (PTH)– Increases Ca++ in the blood– Stimulates osteoclasts
• 1,25 Vitamin D3– Increases Ca++ in the blood– Increase Ca++ uptake from the gut– Stimulates osteoclasts
Renal tubular reabsorption of Calcium
80-85 of calcium is reabsorbed at proximal tubule and medullary loop of henle (passive transportAccording to physiologic needsat the DISAL tubule and adjacent cortical thick ascending limb ( where PTH, Vit D exert its effect)
CCT—cortical collecting tubule; IMCD—inner medullary collecting duct or tubule; PST—proximal straight tubule.
Renal tubular reabsorption of phosphorus
Most of the inorganic phosphorus in serum is ultrafilterable at the level of the glomerulus.
CCT—cortical collecting tubule; IMCD—inner medullary collecting duct or tubule; PST—proximal straight tubule.
MAINTENANCE OF CALCIUM AND PHOSPHATE HOMEOSTASIS
• It is dependent on– Intestinal– Bone– Renal function
MAINTENANCE OF CALCIUM AND PHOSPHATE HOMEOSTASIS
• It is dependent on– Intestinal– Bone– Renal function
Na Cl and KCL complete absorbtion at intestine but CALCIUM AND PHOSPHATE is incomplete
* because of the requirement for vitamin D and formation of insoluble salts like; Calcium phosphate,calcium oxalate and magnesium phosphate at the intestinal lumen
Calcitonin Is synthesized by
parafollicular cells of thyroid gland
Affects the metabolism of Са and Р - Promotes the transferring of Са2+ from
blood into bones- Inhibits reabsorption of Р in kidneys
(decreases the content of Р in blood due to its excretion with urine)
Increase of calcitonin
- hypocalciemia- hypophosphatemia- hyperphosphaturia
Decrease of calcitonin- hypercalciemia- hyperphosphatemia- hypophosphaturia
PARATHYROID GLANDS Parathyroid hormone - protein
Affects the metabolism of Са and Р
- Promotes moving of Са2+ from bones into blood
- Inhibits reabsorption of Р in kidneys (decreases the content of Р in blood due to its excretion with urine)
- Stimulates the absorption of Ca in the intestine
Дія зв’язана з вітаміном D (утворює активну форму вітаміну D в нирках)
2 Main regulators of Calcium and phosphorus:
PARATHYROID HORMONE Vitamin D1. PTH ( Parathyroid
hormone) 84 amino peptide Molecular mass if 9.5
kilodalton no carbohydrate or other
covalently bound molecules Full biologic activity resides
in the amino terminal third of the molecule
PTH 1-34 has full biologic activity while region 25-34 is for receptor binding
• Is a fat soluble steroid• That is present in the diet
and can be synthesized from the skin
PARATHYROID HORMONE• A polypeptide
secreted from the parathyroid glands in response to a decrease in the plasma concentration of ionized calcium
Parathyroid Hormone
Precursor of PTH are:
A. PreproPTH differs from proPTH by having additional 25 amino acid amino terminal
* it is the hydrophobic
end• *at Rough endoplasmic
reticulum
Parathyroid Hormone
• Precursor of PTH are:
B. ProPTH differs from native hormone by having an amino terminal highly basic hexapeptide extension
* it is hydrophobic end
* at PTH golgi apparatus
PTH increases Ca concentration by:• 1. In the presenc e of
permissive amounts of vitamin D it stimulates bone resorptionrelease of calcium phosphates
• 2. Enhances intestinal Calcium and phosphate absorption promotes formation of vit D
• 3. It augments renal calcium reabsorption
PTH
• Regulation of Synthesis– Biosynthesis is regulated by levels of calcium– An acute decrease of Ca results in marked increase of PTH
mRNA increase of PTH synthesis– Effects is at the level of gene transciption, MRNA stability,
mRNA translation– Rate of degradation of PTH is low if low calcium and high if
calcium is high– 1, 25 (OH)2D3 receptor complex binds with vitamin D in the
promoter region of PTH gene and inhibits transcription decreases the production of PTH
– PTH synthesis can be enhanced by the size and number of PTH producing chief cells in cases of prolonged hypocalcemia
Hyperfunction (Recklinghausen’s disease)
- hypercalciemia- hypophosphatemia- hyperphosphaturia- osteoporosis- Accumulation of Са
in tissues
Hypofunction- hypocalciemia- hyperphosphate
mia- hypophosphaturia- tetanus
Hyperparathyroidism: adenoma or hyperplasia or ectopic
Hypocalcemia
Regulation of Metabolism and synthesis of 1,25()H)2-D3
Primary RegulatorsPrimary Regulators Secondary Secondary RegulatorsRegulators
Hypocalcemia (Hypocalcemia (↑)↑)
PTHPTH((↑)↑)
HypophosphatemiaHypophosphatemia((↑)↑)
Calcitriol (↓)Calcitriol (↓)
EstrogenEstrogen
AndrogensAndrogens
ProgesteroneProgesterone
InsulinInsulin
Growth HormoneGrowth Hormone
ProlactinProlactin
Thyroid HormoneThyroid Hormone
1,25 Vitamin D3• Increases Ca++ uptake from the gut
– Increase transcription and translation of Ca++ transport proteins in gut epithelium
• Minor roll: also stimulates osteoclasts– Increase Ca++ resorption from the bone
Cholesterol precursor 7-dehydrocholesterol
UV
Vitamin D3
25 Vitamin D3
1,25 Vitamin D3
Low plasma Ca++ increase kidney enzymes
Images of RicketsImages of Rickets
Rachitic Rosary
Wrist expansion: cupping and fraying of hypertrophied metaphyseal plate
Rotten-stump epiphysisBone demineralization and deformity