The Movement of Fluid Across the
Plasma Membrane
• Describe the role of aquaporins in water movement
across membranes.
• Define and explain osmotic and hydrostatic forces.
• Calculate the osmotic pressure gradient.
• Define and explain tonicity.
• Discuss the effect of hypertonic, isotonic and hypotonic
-solutions on cell volume.
• Define non-penetrating, rapid penetrating and slow
penetrating solute
• Describe the effect of the administration of various IV
fluids on the internal environment.
The Movement of Water Across the
Plasma Membrane
•Water can move in and out of cells.
•But the partition coefficient of water into lipids is low meaning
the permeability of the membrane lipid bilayer for water is low.
•Specific membrane proteins that function as water channels
explain the rapid movement of water across the plasma
membrane
•These water channels are small integral membrane proteins
known as aquaporins
Water Movement
NaCl 0 mOsm
NaCl 100 mOsm
[water] HIGH
[water] LOW
Aquaporin
If membrane impermeable to NaCl
CLINICAL CORRELATION•In the kidney, aquaporin-2 (AQP2) is abundant in the collecting duct and is the
target of the hormone vasopressin, also known as antidiuretic hormone. This
hormone increases water transport in the collecting duct by stimulating the
insertion of AQP2 proteins into the apical plasma membrane. Several studies
have shown that AQP2 has a critical role in inherited and acquired disorders of
water reabsorption by the kidney.
• For example, nephrogenic diabetes insipidus is a condition in which
the kidney loses its ability to reabsorb water properly, resulting in excessive loss
of water and excretion of a large volume of very dilute urine (polyuria).
Although inherited forms of diabetes insipidus are relatively rare, it can develop
in patients receiving chronic lithium therapy for psychiatric disorders, giving rise
to the term lithium-induced polyuria.
• Both of these conditions are associated with a decrease in the number of
AQP2 proteins in the collecting ducts of the kidney.
Osmosis
- Osmosis is the flow of water across a
semipermeable membrane from a solution with
low solute concentration to a solution with high
solute concentration.
• The driving force for the movement of water
across the plasma membrane is the difference in
water concentration between the two sides of
the membrane.
• For historical reasons, this driving force is not
called the chemical gradient of water but the
difference in osmotic pressure.
• The osmotic pressure of a solution is defined as
the pressure necessary to stop the net
movement of water across a selectively
permeable membrane that separates the solution
from pure water.
The Movement of Water Across the Plasma Membrane Is Driven
by Differences in Osmotic Pressure
•Osmotic pressure of a solution is defined as the pressure necessary to
stop the net movement of water across a selectively permeable membrane
•When a membrane separates two solutions of different osmotic pressure,
water will move from –
the solution with low osmotic pressure (high water and low solute
concentrations) to
the solution of high osmotic pressure (low water and high solute
concentrations).
The osmotic
pressure of a solution can be calculated by -
Van't Hoffs law, which states that osmotic pressure depends on the
concentration of osmotically active particles. The concentration of
particles is converted to pressure according to the following equation:
where:
osmotic pressure (mm Hg or atm)
g = number of particles in solution
7T =
R = gas constant (0.082 L-atm/mol-K)
σ = Reflection coefficient (varies from 0 to 1)
T = absolute temperature (K)
C = concentration (mol/L)
Reflection coefficient (σ)
• is a number between zero and one that describes
the ease with which a solute permeates a
membrane.
• a. If the reflection coefficient is 1, the solute is
impermeable. Therefore, it is retained in the
original solution, it creates an osmotic pressure,
and it causes water flow. Serum albumin (a large
solute) has a reflection coefficient of nearly one.
• b. If the reflection coefficient is 0, the solute is
completely permeable. Therefore, it will not exert
any osmotic effect, and it will not cause water
flow. Urea (a small solute) has a reflection
coefficient of close to zero and it is, therefore, an
ineffective osmole
Osmolarity refers to osmotic pressure
generated by the dissolved solute molecules in 1L
of solvent.
It depends strictly on the number of particles in solution
(not the number of molecules, since some molecules (e.g.
NaCl) dissociate into ions when in solution).
Osmolarity is therefore, the number of particles per liter of
solution and is expressed in osmol/L or OsM or in the
case of dilute solutions as milliosmol/L.
Ex- A solution of 1 M CaC12 has a higher osmotic pressure
than a solution of 1 M KCl because the concentration of
particles is higher.
The higher the osmotic pressure of a solution, the greater the
water flow into it.
Units of concentration
• mOsm (milliosmolar) or mOsm/L = an index of
the concentration of particles per liter of solution
• mM (millimolar) or mM/L = an index of the
concentration of molecules dissolved per liter of
solution
• isotonic solutions = 300 mOsm = 150 mM NaCl
(one NaCl molecule yields two particles in
solution)
• 300 mOsm = 300 mM glucose
Osmolality and Tonicity
• A solution’s osmolality is determined by the
total concentration of all the solutes present.
• In contrast, the solution’s tonicity is
determined by the concentrations of only
those solutes that do not enter(“penetrate”)
the cell
Osmolarity
•
Two solutions having the same effective osmotic pressure are
isotonic because no water flows across a semipermeable
membrane separating them.
•
If two solutions separated by a semipermeable membrane have
different effective osmotic pressures, the solution with the
higher effective osmotic pressure is hypertonic and the solution
with the lower effective osmotic pressure is hypotonic.
• Water flows from the hypotonic to the hypertonic solution.
RBC hypotonic solution
Rules for predicting tonicity
If the cell has a higher concentration of non-penetrating solutes than the
solution, there will be net movement of water into the cell. The cell swells,
and by definition that solution is hypotonic.
SWELL
RBC isotonic solution
NO VOLUME CHANGE
RBC hypertonic solution
SHRINK
Tonicity
Tonicity describes the volume change of a cell
placed in a solution
Problems involving a non penetrating
solute
• Predict the changes in cell volume (increase,
decrease, no change) when a normal RBC
previously equilibrated in isotonic saline is placed
in the following solutions.
• Assume the fluid volume of the external solution
is large, and thus, as water moves in or out of the
cell, there is no significant change in the
concentration of beaker solutes .
1. 200 mOsm NaCl
2. 400 mOsm NaCl
3. 150 mM NaCl
4. 300 mM NaCl
Effect of substances that rapidly
penetrate cell membranes
• The presence of a substance, such as urea, ,5%
dextrose that penetrates the cell membrane
quickly does not affect the osmotic movement
of water.
• If the total concentration of non penetrating
solutes is <300 mOsm, the RBC will swell; if it
is >300 mOsm,the RBC will shrink.
Problems involving a rapidly
penetrating solute
• Predict the changes in cell volume (increase,
decrease, no change) when a normal RBC
previously equilibrated in isotonic saline is
placed in the following solutions:
1. 200 mOsm NaCl and 200 mOsm urea
2. 300 mOsm urea only
3. 500 mOsm urea only
Effect of substances that slowly
penetrate cell membranes
• Some substances( glycerol) penetrate cell membranes
but do so slowly.
• Thus, they initially have an osmotic effect like sodium
chloride but no osmotic effect at equilibrium.
• Problem involving a slowly penetrating solute
Q.Predict the changes in cell volume (increase, decrease,
no change) when a normal RBC previously equilibrated
in isotonic saline is then placed in the following
solution. Determine the initial effect versus the longterm effect.
• 200 mOsm NaCl and 200 mOsm glycerol (a slowly
penetrating substance)
The Clinical Relevance of Understanding Tonicity
The importance of understanding this well is to make sure that you
understand the basis and rationale for intravenous fluid therapy.
Several IV fluids exist e.g.
0.9% saline(normal saline)
5% dextrose in normal saline
5% dextrose in water
half normal saline
5% dextrose in half normal saline. (Dextrose is glucose).
How does the clinician decide which fluid to use? Well, it depends
on what the objectives are – replacement of blood volume or
rehydration of cells in dehydrated individuals.
Discussion on IV solutions
First thing to do is to look at the relative osmolarity and
tonicity of the solution to the extracellular (and intracellular) fluid.
Then take into account what effect this will have on the volumes of
the two fluid compartments.
1. 0.9% saline. This has the same osmolarity as the intracellular
fluid. The saline is NaCl so the two particles Na and Cl are
considered to be non-penetrating. Therefore this solution is isoosmotic and isotonic. Because it is isotonic it will not change the
tonicity of the extracellular fluid and so the extracellular fluid will
remain isotonic to the intracellular fluid. Therefore NO FLUID
MOVEMENT INTO THE CELLS. This solution would be suitable for
replacing blood (extracellular fluid).
2.
5% Dextrose in normal saline. 5% dextrose is iso-osmotic to the intracellular
fluid, so is normal saline. Therefore you must take into account both of these
when working out the overall osmolarity. This solution has twice the
osmolarity of the intracellular fluid. Therefore it is HYPEROSMOTIC.
Dextrose is penetrating , so makes no contribution to the tonicity of the
solution. Saline is non-penetrating it does make a contribution. Therefore
the solution is ISOTONIC. Infusion of this solution into the veins would not
change the tonicity of the extracellular fluid so NO NET FLUID MOVEMENT
INTO THE CELLS. Notice the NET. Rapid infusion of this solution will lead
initially to some water movement out of the cells which will be reversed as
the dextrose moves into the cells. This solution would be suitable for
replacing blood.
3.
5% Dextrose in water. 5% dextrose is iso-osmotic to the intracellular fluid.
Water is, of course, hypo-osmotic (0 mosm)(it has no particles). This solution
therefore is iso-osmotic to the intracellular fluid. Water has no tonicity and
dextrose is penetrating . This solution has no tonicity so is HYPOTONIC to the
intracellular fluid. Infusion of this solution will make the extracellular fluid
hypotonic to the intracellular fluid so some of the infused fluid will enter the
cell. THERE IS THEREFORE FLUID MOVEMENT INTO THE CELLS. This solution
would be suitable for rehydrating cells.
4. Half normal saline. This is 0.45% saline, so has half the number
of particles as normal saline so it is hypo-osmotic to the
intracellular fluid. The particles are non-penetrating but again
you have half the number of particles. This solution is therefore
HYPOTONIC to the intracellular fluid. Infusion of this solution
will make the extracellular fluid hypotonic to the intracellular
fluid so some of the infused fluid will enter the cell. THERE IS
THEREFORE FLUID MOVEMENT INTO THE CELLS. This solution
would be suitable for rehydrating cells.
5. 5% Dextrose in half normal saline. 5% dextrose is iso-osmotic
to the intracellular fluid, half normal saline is hypo-osmotic.
However if you have them together in a solution the result is
hyperosmotic to the intracellular fluid. Only the saline is nonpenetrating , therefore the solution is HYPOTONIC to the
intracellular fluid. Infusion of this fluid will decrease the tonicity
of the extracellular fluid. THERE IS THEREFORE FLUID MOVEMENT INTO
THE CELLS. This solution would be suitable for rehydrating cells.
In order to replenish the fluid and electrolyte
loss in diarrhoea, a person is given ORS. Of the
following composition of ORS, which of the
following along with Na is more important for
replenishing Na loss?
a. K
b. Cl
c. Glucose
d. Citrate
Oral Rehydration Therapy Is Driven by Solute
Transport
Oral administration of rehydration solutions has dramatically
reduced the mortality resulting from cholera and other diseases that
involve excessive losses of water and solutes from the
gastrointestinal tract. The main ingredients of rehydration solutions
are glucose, NaCl, and water. The glucose and Na+ ions are
reabsorbed by SGLT1 and other transporters in the epithelial cells
lining the lumen of the small intestine .
Deposition of these solutes on the basolateral side of the epithelial
cells increases the osmolarity in that region compared with the
intestinal lumen and drives the osmotic absorption of water.
Absorption of glucose, and the obligatory increases in absorption of
NaCl and water, helps to compensate for excessive diarrheal losses
of salt and water.