the composition of different body compartment is really important for
maintaining homeostasis this is the media where all our cells
communicate with and interact with and actually this media is contained
inside the cells too . so the composition of all these compartments
maintaining a balance of the composition either water or the solutes
and the components of these compartment is really important and
there are several mechanisms to regulate the components of all these
compartment as well as the water (the solvent) .
Also NaCl is the main factor that governs the movement of water ,so it's
important and a main factor for maintaining homeostasis , also the
kidney it's the major regulator of fluid homeostasis and by toning NaCl
excretion and as a result water it can regulate, it can affect, it can
balance any changes in the homeostasis of fluid . to obtain a balance
between water gain(intake) and water excretion(out put ).
NOTE :
*** calculation that we took them in the last lecture they are important
and included in the exam so we expect to be required to calculate or to
estimate the volume of one compartment by knowing the mass( body
weight)***it’s very important for us as a pharmacists
# The mechanisms for regulating water and solutes in the body:
1. Rennin - angiotensin II system : (this had been explained previously
but there are some important additional information you have to
know )
the hypotension (which is the decrease in blood pressure due to
decrease in the volume of fluid or there is an increase in the loss of
water or there is an hemorrhage )this will cause a lower in the
perfusion (which reflects the hypotension ) of the blood that reach to
the kidney so this stimulate the secretion of renin from cells exist in the
nephrons)
then renin goes to the blood to find it’s substrate which is
(angiotensinogn ) then produce (angiotensin I) after that there is an
enzyme called (Ase )which responsible for the formation of
(angiotensinII ) ,then it will bind to it is receptor it increase the
reabsorbtion of Na + in the kidney then it Increase the reabsorption of
water because Na+ is the most important electrolyte that determine the
movement of water ,NaCl where ever it’s goes it affect the osmolarity of
that compartment so it should be followed by water (water follows
solutes ) to have a balance SO we will have an increase in the blood
pressure (this is only one function of angio.II) .
Now because there is no action without receptors this is very important
to know how drugs work ,and this is the concept of the mechanism of
(antihypertensive) drugs that cause a block for the receptors for
angiotensin II so it prevents it’s action by the way we decrease the
blood pressure in case of hypertension (increase in the blood pressure
‫وظيفته يرفع الضغط ف هذا الدواء مضاد ارتفاع الضغط يعمل على‬II ‫)النه اصال انجيوتنسن‬
II( ‫تقليل ضغط الدم من خالل اغالق مستقبالت انجيوتنسن‬
2. Aldosteron: may stimulated by angiotensin II, which is stimulated
according to the hypotension (decrease in the blood pressure ) and the
aldosteron, in response to angio.II, is then secreted from the adrenal
gland specifically from the( adrenal cortex )and it increase the re
absorption of Na+ and it has another action on K+
,so it increase NaCl reabsorption followed by water to increase the
volume of blood so the blood pressure .
3.Atrial naturetic peptide (ANP): it work in the opposite direction of
(aldosteron and angio.II) it work to reduce blood pressure , so (ANP) it
does like antihypertensive drugs but it’s a natural one , by natriuresis
Means increase Na+ loss and as a result water loss so it works like
diuretic. Or in other words : elevated urinary excretion of Na + and (Cl- )
followed by water excretion which decrease blood volume. by increase
the loss of water in urine .
4.Antidiuretic hormone (ADH) : which involving in increase the blood
pressure also it stimulated by( angio.II),it’s synthesis in the
hypothalamus and then transported and stores in the posterior pituitary
gland from there it will be secreted when it stimulated by (angio.II) or a
stimulus from osmoreceptors which they detect high osmolarity ,like
the osmoreceptors of the thirst center. So antiduretic hormone it called
(neural hormone ) because the synthesis by neurons in the
hypothalamus ,unlike anterior pituitary hormones which they formed
from a gland .
The action of (ADH) goes to the kidney by the blood specifically to the
collecting duct (it’s the last segment in the nephron ) which carried the
last toning to the composition of urine so this segment usually reach to
it the tubular fluid which will be urine ( ‫ )السائل المترشح‬when it arrives to
the collecting duct it will be very diluted because a huge reabsorption
happened until we reach this state . so the urine will be very diluted in
this case anti diuretic hormone is stimulated and transported by blood
to reach the kidney to the tube it will works on the cells that composed
of the these segments and promote the insertion of transporters
specialized for water called (aquaporins) , water –channel proteins , in
the collecting ducts of the kidneys (this segment ) as a result the
permeability of it to water increase by these aquaporins ,because the
phospholipids bilayer membrane is hydrophobic so the movement of
water can’t happen without these channels ,so when it become inserted
it will be permeable for water and according to the osmosis the urine is
very diluted so water will go out of this duct and reabsorbed in the
capillaries surrounding the collecting ducts so that’s why it’s called
antidiuretic ) ‫ ( المانع إلدرار البول‬so with the absence of this hormone the
urine would be very diluted and in large amounts . so it will make a
direct reabsorption for water because we need this hormone to obtain
balance by turn back the water to the blood ;because there is a high
osmolarity in the interstitial fluid or there is an depression in the blood
pressure so it help to increase blood pressure that’s why it’s stimulated
by angio.II because it’s tray to exploit the whole pathways to increase
the blood pressure .
we discussed osmolarity and osmosis
and osmosis means the movement of water molecules across a semi
permeable membrane and if this membrane is not permeable for
certain solute and there were differences in the osmolarities across the
membrane then water will move to which direction ? to the lower
osmolarity or to the higher osmolarity ?
the water will move to the higher osmolarity from the lower osmolarity
NOTE: osmolarity here refers to the concentration of the solute and the
solutes that usually can't cross the membrane " that can make
gradients"
and now we will see the constituents of different compartments and see
how the gradient appears .
so here comes the term effective osmols .. what does the effective
osmols mean ? .. it means that the concentration of the solutes that can
cause water movement , that can be greater at a side than another side ,
that can't penetrate the membrane easily , that has a gradient .. they are
the effective osmols
on the other hand .. the noneffective osmols such as urea and glucose ..
they can freely move across the membrane so any change in their
concentration in one of the compartments .. it doesn't necessarily
require water to move .. to obtain the balance .. they can move and
make the balance .. that is why we call them noneffective osmols – urea
and glucosethere is plenty of transporter for them so any changes in their
concentration in one compartment , they just can go to the other
compartment to make the balance but sodium chloride –NaCl- its
movement is not easy ( they are sodium ions) they can not cross the
hydrophobic membrane easily and the transporter for it are known and
the main transporter that regulates their movement is called sodium
potassium ATPase channel and this channel (sodium potassium ATPase
channel ) always works to make a gradient for sodium and potassium ,
so they always appear as gradient (one side there is concentration of
sodium is higher than the other side of the membrane ) and now we will
explain which one exactly
 Back to the slide ()
so this is the distribution of some cations and anions across the
intracellular and extracellular membrane and as you can see here ,
let's focus on the intracellular now , potassium is the main or major
cation in the intracellular compartment , opposing it the sodium in
the extracellular compartment
so we notice that the majority of potassium is in the intracellular and
the majority of sodium is in the extracellular .. why ?? because of that
pump which we already mentioned  sodium potassium pump is
located at all of the cells and plays an important role in maintain this
gradient .. this gradient is not just important in the osmolarity and
the fluid homeostasis , it is important for other functions for the cell .
it is used for other functions such as transport for different things , it
is as underlying energy ( ‫ )طاقة كامنة‬which is used for other processes
so calcium is mainly in extracellular – its amount is not large – the
second after calcium is chloride it is anion , and the main anion in the
intracellular is phosphate and organic anions , proteins also
constitute primarily – a major constituent – of the intracellular
rather than extracellular .. notice that the biocarbonate is
extracellular rather than intracellular .. so we really mean to focus on
these differences – between intracellular and extracellular – what
are the cations an anions , which is mainly in the extracellular and
which is mainly in intracellular
however we sum up all the osmolarities of these effective osmols 
we reach equilibrium .. in most cases they are in equilibrium , the
sum of osmolarities are ( ‫– )متعادلين‬intracellular and extracellularhowever the composition is different but the total osmolarities
across the membrane has to be at equilibrium status .. and the
amount of the anion and cation ( the total of cations inside = the total
of cations outside and the total of anions inside = the total of anions
outside ) .. so there is an equilibrium however the composition is
different
Q from a student -- After this , how does action potential occur ?
Action potential is another topic and is a different application for
neuronal sense and it is just happens for moments , at the end , the
equilibrium will happen when action potential finishes ..
At the membrane potential inside the cell usually at rest status is
negative .. so when we talk about the resting potential from the
anions and the cations part yes there are differences .. now we don't
discuss the action potential which we took at the muscle – we don't
discuss the muscular or neuronal – they have electrical properties of
the membrane which is different from the cell which we discuss
generally .. we don't talk about the cell which makes potential
electrical activity for it , they have special transporters and special
electrical properties for their membrane , we talk about the cells in
general
So as you can see here , we have to have sum up all osmolarities and
now we have to distinguish between the two extracellular
compartments which are the blood plasma and interstitial fluid .. Are
there differences between them or not ?  refer to the slide .. now
the plasma and the interstitial fluid in this slide , notice that the
yellow is the intracellular (we discussed it previously ) , now the
extracellular blue is the interstitial fluid and the red is the plasma ..
Are they the same case as the one we have already known that the
sodium is the highest then the chloride then the bicarbonate then the
protein .. Are they the same for the blood plasma and for the
interstitial fluid ? Notice that they are very close for sodium , very
close for potassium , for magnesium , for chloride , the same for
phosphate and the same for SO4-2 .. Notice where the difference
appears , where is the main difference between these two ? .. In
the proteins , we have way more proteins in the plasma than the
interstitial fluid .. so we can say that this scenario is correct for these
two compartment the interstitial fluid and plasma in response to the
extracellular
Did you understand what we mean ? .. we said that the extracellular
compartment consists of two subcompartments –blood and
interstitial fluid- , when we talked previously , we talked about the
extracellular in general , but now we want to know if that the two
subcompartments of the extracellular fluid apply the same (Do they
have the same quantities of the proteins or of the sodium ?) Are they
mirror image of the same extracellular as whole ? NO, we found that
there is just a difference of the protein composition , in the plasma
there are higher proteins than the interstitial fluid , notice it is
significantly different , the difference is so large not simple
So why is that difference , what is the physiological relevant of this
difference ? we know that there is always exchange between the
blood and the interstitial fluid ( means that the blood is filtered : the
plasma inter the interstitial fluid ) .. Does everything in the plasma
can go out from the capillaries and go to the interstitial fluid ? NO,
the large proteins stay in the blood vessel and this is the reason of
the difference , the large proteins don't go to the interstitial fluid .. so
the blood plasma and interstitial fluid are not mirror image , they
(seems to be like each other ) but not in the proteins ( ‫يعني االختالف‬
‫بين السائل بين خلوي‬interstitial fluid& plasma ‫يحدث بسبب البروتينات كبيرة‬
‫الحجم التي ال ترشح مع البالزما من الشعيرات الدموية الى السائل بين خلوي‬interstitial
fluid ). All the components must reach the equilibrium except the
proteins (which is higher in the plasma)
What is the physiological relevant of this finding ? .. The existence of
these proteins in one side more than the other side .. what does it
make ? .. it makes pressure which is called osmotic (Oncotic) colloid
pressure .. this osmotic (oncotic ) colloid pressure is responsible for
driving force for exchange or recycle for the filtered fluid to return
back to the circulation .. and other force which makes the fluid flow
out from the capillaries to the interstitial fluid is the hydrostatic
pressure
The force which is responsible for returning the fluid which carries
the waste products and CO2 to return them to the circulation 
there is no hydrostatic pressure from the interstitial fluid to the
circulation so the force is the colloid pressure , and the existence of
the protein in the vessel makes pressure to make net movement to
inside the capillaries (opposite) .. so this is which makes the recycling
and Venus return … to return to the Venus side of the capillaries
return back to the circulation
Or if the fluid accumulated and it didn't back to the circulation , we
will have edema , so any loss of plasma protein , it will make edema ..
so malnutrition or any problems in the liver – which manufacture the
most proteins in the plasma- ( we will discuss it later ) or seroses or
disease in the liver and the proteins level decreased in the blood , so
there will be generalized edema ..Of course there are other causes
(cardiovascular causes) but now we talk about this concept .. why it is
important to have osmotic onpotic colloid pressure ?? … this is the
difference between interstitial fluid and blood
NOTE : interstitial fluid is between cells and between the cells and the
capillaries , so the spaces which we think that are spaces they are not
, they have fluid which is called interstitial fluid.
NOTE: edema is when the fluids accumulate in the tissues
Now let us apply the concept of movement of water across the
membrane , usually cells should not shrink or swell , they should be in
equilibrium , no net movement of water from one side to the other
side , but sometimes changes occur in our environment in our
physiological status .. such as we drank a lot of water , we sometimes
may drink more water than the kidney's ability to (excrete ) that
water , faster than the ability of kidney to gets out the excess of
water
So what happens ? A dilution , the volume increased and the kidney
should get out all of the excess water but if it exceeds its ability , then
the dilution would happen to our blood and the osmolarity in the
blood would decrease because the water which is the solvent
increased
Now the osmolarity of the blood decreased and the blood is facing
cells and the interstitial fluid , so what will happen ? there will be net
movement , because there we should have balance , so the water will
move from the blood to the interstitial fluid first , then to inside the
cells to make equilibrium , so what will happen for the cell is swelling
, so in this situation (which is excessive ) , the cells may swell and
rupture (explode ) .. and this condition may happen for all types of
cells what ever the cell is … this term is called water intoxication .. the
results of water intoxication : disturbances of the nerve system ..the
percentages of the solute which is important in the nerve system
function and bursting of the cells ( coma and convulsions and death )
So that is why when patients go to the hospital and give them fluids ,
they calculate how much the patient took fluid and how much he got
rid of fluids to not give them over the kidney's ability specially when
there is problem in the kidney – the kidney's function –
NOTE : the normal kidney's ability is 125ml/min so any extra will
accumulate in the body
Now the opposite direction , suppose that we have loss of fluids ,
fasting status , there is no water , there is no accessibility for the
water and increasing of the salt intake  so the osmolarity will
increase specially if there is loss of volume of water and when the
osmolarity increased in the blood , the movement of water will be
from inside the cell to the interstitial fluid to the blood  so outside
movement from the cell , so the cell will shrink .. so lose of water
causes shrinkage of cells , loss of cytosol, affects function of the cell ,
also it drop in the blood pressure and this the first thing may affect
on the human hypotential and make him feels dozy and the blood
will not reach the brain which is the most important organ that needs
oxygen and nutrients
So this is just appreciate how changes on the osmolarity are
important in maintaining the body homeostasis
Now the electrolytes – we discussed them – most of them affect on
osmolarity – the exception we have proteins
Of course we know that ions dissolve and dissociate to make –ve and
+ve ions
To measure osmolarity and at the same time taking account to the
charge of the ions , they discovered a unit which is called MEq (milli
equilibrium )
Read about this unit  it gives us indication how many ions or moles
(molarity )in the solution at the same times the charges .. for example
if we have ion its charge is 3 we multiply the concentration of the ion
by the charge of the ion , so if it is one , it will not be affected , if it is
two , 2* concentration for this dissolved ion .. so this unit is
important when we talk about the electrolytes in our bodies (MEq)
What are the functions or the main functions of the electrolytes ? ..
1- to maintain a balance between compartments (osmotic pressure)
,main function
.. 2- some of these electrolytes may act as buffering system , acid
base balance in our bodies , such as bicarbonate phosphate are
important as buffers .. our bodies always produce acids and these
acids should be neutralized …
3- they carry electrical currents in some cells types which have
membrane potential like muscle cells or nerve cells
4.Also they serve as co-factors for many reactions like : Mg +2 in Na +k+ ATPase pump without this ion(Mg +2) this pump can’t work .