Download Hormonal regulation of calcium and phosphorus homeostasis

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
CCT—cortical collecting tubule;
IMCD—inner medullary collecting duct or tubule;
PST—proximal straight tubule.
80-85 of calcium is
reabsorbed at proximal
tubule and medullary loop
of henle (passive transport
According to physiologic
needsat the DISAL
tubule and adjacent
cortical thick ascending
limb
( where PTH, Vit D exert
its effect)
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
1.





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
Vitamin D
• 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
• 1. In the presenc e ofby:
permissive amounts of
vitamin D it
stimulates bone
resorptionrelease 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
hyperphosphatemia
hypophosphaturia
tetanus
Hyperparathyroidism: adenoma
or hyperplasia or ectopic
Hypocalcemia
Regulation of Metabolism and
synthesis of 1,25()H)2-D3
Primary Regulators
Secondary
Regulators
Hypocalcemia (↑)
PTH(↑)
Hypophosphatemia(↑)
Calcitriol (↓)
Estrogen
Androgens
Progesterone
Insulin
Growth Hormone
Prolactin
Thyroid 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
UV
– Increase Ca++ resorption from the bone
Cholesterol precursor
7-dehydrocholesterol
Vitamin D3
25 Vitamin D3
1,25 Vitamin D3
Low plasma Ca++ increase kidney enzymes
Images of Rickets
Wrist expansion: cupping and fraying of
hypertrophied metaphyseal plate
Bone demineralization and deformity
Rachitic Rosary
Rotten-stump epiphysis