Download CALCIUM AND PHOSPHATE METABOLISM

KSU
CALCIUM AND
PHOSPHATE
METABOLISM
Dr.Aida Abdelhamid Korish
Assistant Prof.Physiology Dept.
[PHYSIOLOGY DEPT.KSU]
CALCIUM AND PHOSPHATE METABOLISM
Three hormones are primary concerned with the
regulation of calcium metabolism:
-1,25-dihydroxycholecalciferol (a steroid hormone
formed from vitamin D)
-parathyroid hormone (secreted from the
parathyroid gland)
-cacitonin (secreted from perifollicular cells of the
thyoid glands).
All the three hormones probably operate to maintain the
constancy of the calcium level in the body fluids.
Glucocorticoid,growth hormone,oestrogen and various
other hormones also affect calcium metabolism.
Absorption of calcium and phosphate:
Calcium is actively absorbed in the upper small
intestine,facilitated by 1,25-dihydroxycholecalciferol.
Calcium absorption is adjusted to body needs, absorption
is increased in the presence of calcium deficiency and
decreased in the presence of calcium excess.
calcium absorption is :
 facilitated by lactose and protein,
 inhibited by phosphate and oxalate
because these form insoluble salts with
calcium in the intestine.
Phosphate is absorbed in the duodenum and small
intestine by both active transport and passive diffusion.
when excess calcium is in the deit , the calcium tends to
form insoluble calcium phosphate compounds that fail to
be absorbed.
Function of the calcium in the body:
1.it enter in the structure of
bones,teeth,connective tissue elements and
cellular cement substance.
2.ionized calcium is necessary for blood
coagulation,muscle contraction,and nerve
conduction.
Function of phosphate:
It enter in the formation of many compounds as
ATPand C-AMP.
Vitamin D and its role in calcium and
phosphate absorption:
Vitamin D has a potent effect on increasing calcium
absorption from the intestinal tract,it also has important
effect on bone deposition.
vitamin D is not the active substance,it must first be
converted in the liver and kidneys to the final active
product 1,25 dihydroxycholecalciferol in multiple
steps as the following:
1.vitamin D3(cholecalciferol) is formed in the
skin as a result of irradiation of steroid(7dehydrocholesterol) by ultraviolet rays.
exposure to the sun prevents vitamin D
deficiency.
2. cholecalciferol is converted to 25hydroxychlecalciferol in the liver which has a
feedback inhibitory effect on the conversion
reactions.
Feedback mechanism regulates the
concentration of 25-hydroxychlecalciferol in
the plasma and conserves the vitamin D for
future use because once converted,it persists
in the body for short time but vitamin D can
be stored in the liver for several months.
3.in the kidneys, 25-hydroxychloecalciferol is
converted to 1,25 dihydroxycolecalciferol
which is the active form of vitamin D,this
conversionrequires parathyroid
hormone.parathyroid hormone exerts a potent
effect in determining the functional effect of
vitamin D in the body.
4. 1,25-dihydroxycholecalciferol causes
formation of calcium binding protein in the
intestinal epithelial cells.the rate of calcium
absorption is proportional to the quantity of
calcium binding protein.it remain in the
intestine for several weeks after
disappearance of 1,25dihydroxycholecalciferol.
5.when the plasma calcium concentration is
increased,it inhibits parathyroid hormone
secretion which lead to decrease formation of
1,25- dihydroxycholecalciferol.
.lack of this in turn decreases the absorption
of calcium from the intestines,from the renal
tubules,thus causing the calcium ion
concentration to fall back tward its normal
level.
1,25- dihydroxycholecalciferol itself functions
as a hormone to promote intestinal absorption
of calcium.
Figure:activation of vitaminD3 to form 1,25dihydroxycholecalciferol, and the role of vitamin D in
cotrolling the plasma calcium concentration
The concentration of calcium in the plasma is 9.4
mg/dL,varying between 9.0 and 10.0 mg/dL.
The calcium in the plasma is present in three different
forms:
1.40% of the calcium is combined with the plasma
proteins(is non-diffusible through the capillary
membrane).
2.10% of the calcium is diffusible through the
capillary membrane but is combined with other
substances of the plasma and interstitial fluids in
such a manner that it is not ionized.
3.The remaining 50% of the calcium in the
plasma is both diffusible through the capillary
membrane and ionized.this ionic calcium is
important for most functions of calcium in the
body,including the effect of calcium on the
heart,on the nervous system, and on bone
formation.
Bone calcium and its relationships to extracellular
calcium and phosphate
Bone is composed of tough organic matrix that is
greatly strengthened by deposits of calcium salts.
the crystalline salts deposited in the organic matrix
are composed principally of calcium and phosphate
in the form of hydroxyappitite crystals.
about 0.5-1% of the total bone calcium is in the
form of readily metabolizable amorphous calcium
phosphate known as exchangeable calium that is
always in equilibrium with calcium ions in the
extracellular fluids.it provides a rapid buffering
mechanism to keep the calcium ion concentration of
extracellular fluids from rising to excessive levels
or falling to very low levels.
In addition to the buffer function of bones,the mitochondria
of many of the tissues of the body,especially of the liver and
intestine,also contain a reasonable amount of exchangeable
calcium that provide an additional,buffer system for helping
to maintain constancy of extracellular fluid calcium ion
concentration.
Parathyroid gland
There are four parathyroid glands in human being;located
immediately behind the thyroid gland.
the parathyroid gland of the adult human contains chief cells
and oxyphil cells.
the chief cells secrete most of the parathyroid
hormone(parathormone).
Action of parathyroid hormone:
The effect of parathormone is elevation of calcium ion
concentration in the extracellular fluid and depression of
phosphate concentration.bone,kidney and GIT are the
three organs affected by parathormone.
A) effect on bone:
parathyroid hormone has two separate effect on bone
in causing absorption of calcium and phosphate.
1.a very rapid phase that takes place in minutes
and results from activation of the already
existing bone cells(osteoclast) to promote calcium
and phosphate absorption.
2. a slower phase requiring days or even weeks
to become fully developed results from
proliferation of the osteoclast,followed by by
greatly enhanced osteoclastic reabsorption of the
bone itself.
B)Effect on the kidneys:
1. Adminstration of parathyroid hormone causes
immediate and rapid loss of phosphate in urine by
diminished proximal tubular reabsorption of
phosphate ions.
2. parathyroid hormone increases the absorption
of calcium in the proximal tubules and collecting
ducts.
C)Effect on the intestine:
It enhances both calcium and phosphate
absorption from the intestine by increasing the
formation of 1,25 dihydroxycholecalciferol from
Vit.D.
Control of parathyroid hormone secretion:
1.the slightest decrease in calcium ion concentration in the
extracellular fluid causes the glands to increase the rate of
secretion within minutes, and if the decreased calcium
concentration persists ,the gland will hypertrophy.
2.Any condition that increases the calcium ion concentration
causes decreased activity and reduced size of the parathyroid
gland such as :
a)Excessive amount of calcium in diet.
b)Increased Vit.D in the diet.
c)Bone absorption caused by factors other than parathyroid.
Hyperparathyroidism
When the parathyroid glands do not secrete sufficient
hormone,the osteoclast of the bone become inactive.as a
result,bone reabsorption decrease so the level of calcium in the
body fluid decreases.
When the parathyroid glands are suddenly removed, the
calcium level in the blood falls from the normal of 9.4 to 6
mg/dL within two to three days (hypocalcemia which leads to
tetany)
Causes of tetany:
When the extracellular fluid concentration of
calcium ion falls below normal,the nervous system
becomes more excitable because of increased
neuronal membrane permeability to sodium ions.
this increase in excitability occurs both in CNS and
in the peripheral nerves.
The nerve fibres becomes so excitable that they
begin to discharge spontaneously,initiating nerve
impulses that pass to the peripheral skeletal
muscles causing extensivespasm involving especially
the muscles of the extremities and the
larynx.laryngospasm becomes so severe that the
airway is obstructed and fatal asphyxia is
produced.
Tetany in the hand occur before generalized tetany develop ,
this is called carpal spasm.
Acute hypocalcemia in human being causes no other
significant effects beside tetany,because tetany kills the
patients before other effects can develop.
Types of tetany:
1.manifest tetany:
which shows itself without any stimulus to evoke it.the serum
calcium is less than 7mg/dL.
2.latent tetany:
the serum calcium ions is about 7mg/dL.this type of tetany
needs certain tests to prove it.
a)Chovostek,sign:quick contraction of theipsilateral facial
muscles elicited by tapping over the fafacial nerve at the angle
of the jew.
b)Trousseau,sign: occlusion of the circulation with a blood
pressure cuff causes a spasm of the muscles of the upper
extremity which causes flexion of the wrist and thumb with
extension of the fingers(carpal spasm).
Because placing a tourniquet on the upper arm causes ischemia
of the peripheral nerves and also increases the excitability of
the nerves thus causing spasm of the muscles of the lower arm
and hand.
Hyperparathyroidism
The cause of Hyperparathyroidism : IT IS THE TUMOUR OF
ONE OF THE PARATHYROID GLANDS.
In Hyperparathyroidism,extreme osteoclastic activity occurs in
the bone and this elevated the calcium ion concentration in the
extracellular fluid,which usually depressing the concentration
of phosphate ions because of increased rate of excretion of
phosphate.
Bone disease in Hyperparathyroidism
In severe hyperthyroidism, the osteoclastic absorption is
severe,bone may be eaten away with development of large
cavities filled with very large multinucleated osteoclast.
radiographs of the bone show extensive decalcification.
multiple fractures can result from slight trauma.
Effect of hypercalcemia:
in Hyperparathyroidism calium level increases which leads
to:
 depression of the central and peripheral nervous system.
 muscular weakness.
 constipation,abdominal pain,peptic ulcer and loss of
appetite because of depressed contractility of the muscle
wall of the gastrointestinal tract.
 depressed relaxation of the heart during diastole.
If the level of calcium in the body fluid rises to very high
level, calcium,phosphate crystal may be deposited in:
 the alveoli of the lung.
 in the tubules of the kidneys.
 in the wall of the arteries.
this effect can be fatal.
Calcitonin
This hormone reduces the blood calcium ion concentration.it is
secreted in the human being by the thyroid gland from
perifollicular cells.
Calcitonin is a protein in nature.
Functions of Calcitonin:
Calcitonin Reduces plasma calcium concentration in three separate
ways:
1.it reduces bone resorption by inhibiting
osteoclast function.this result in a decrease in the
concentration of both calcium and phosphate in
serum.
2.it increases the urinary excretion of calcium
,phosphate,sodium,potassium,and magnesium.
3.the third and most prolonged effect of calcitonin
is to decrease the formation of new osteoclast.
Calcitonin has only a very weak effect on plasma calcium
concentration in the adult human being.
on the other hand,the effect in children is much more marked
because bone remodeling occurs rapidly in children,with
absorption and deposition of calcium.
There are two major differences between the calcitonin
and the parathyroid feedback system:
1.the Calcitonin mechanism operates more rapidly.
2.the Calcitonin mechanism acts mainly as a shortterm regulator of calium `ion concentration because
it is very rapidly overridden by the much more
powerful parathyroid control mechanism.
Control of Calcitonin secretion:
1.increase in plasma calcium concentration of about
10%,causes an immediate three-to six fold increase in the
rate of secretion of calcitonin.
2. dopamine and estrogens stimulates Calcitonin secretion.
3.gastrin.cck,glucagons and secretin stimulate Calcitonin
secretion.
↑ Ca++
dopamine }
estrogen } →
↓ Calcitonin
→
↑
calcitonin