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Hormonal regulation of calcium

and phosphorus homeostasis.

Modul Fungsi Normal Digesti dan


Metabolik-Endokrin 2016-2017
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
transport
According to
physiologic needsat
the DISTAL tubule
and adjacent cortical
thick ascending limb
CCTcortical collecting tubule;
(where PTH, Vit D
IMCDinner medullary collecting duct or tubule; exert its effect)
PSTproximal straight tubule.
Renal tubular reabsorption of
phosphorus

Most of the inorganic


phosphorus in serum is
ultrafilterable at the
level of the glomerulus.

CCTcortical collecting tubule;


IMCDinner medullary collecting duct or tubule;
PSTproximal 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 Na Cl and KCL


complete absorbtion at
Intestinal intestine but CALCIUM
AND PHOSPHATE is
Bone incomplete
Renal function * 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 and


- Promotes the transferring of 2+ from
blood into bones
- Inhibits reabsorption of in kidneys
(decreases the content of 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 and
- Promotes moving of 2+
from bones into blood
- Inhibits reabsorption of
in kidneys (decreases the
content of in blood due
to its excretion with
urine)
- Stimulates the absorption
of Ca in the intestine
2 Main regulators of Calcium and
phosphorus:
PARATHYROID HORMONE Vitamin D
1. PTH ( Parathyroid Is a fat soluble steroid
hormone)
84 amino peptide That is present in the diet
Molecular mass if 9.5 and can be synthesized
kilodalton from the skin
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
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
Hypofunction
Hyperfunction - hypocalciemia
(Recklinghausens - hyperphosphatemia
disease) - hypophosphaturia
- hypercalciemia - tetanus
- hypophosphatemia
- hyperphosphaturia
- osteoporosis
- Accumulation of
in tissues
Hyperparathyroidism: adenoma
or hyperplasia or ectopic
Hypocalcemia
Regulation of Metabolism and
synthesis of 1,25()H)2-D3
Primary Regulators Secondary
Regulators
Hypocalcemia () Estrogen
PTH() Androgens
Hypophosphatemia() Progesterone
Calcitriol () 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
Rachitic Rosary

Bone demineralization and deformity Rotten-stump epiphysis

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