Consider the Distribution & Excretion of 1,000 mls of various
As an exercise in applied fluid physiology is to
compare the distribution and excretion of a rapid intravenous
infusion of 1000 mls of various fluids. This serves to emphasise
some of the factors involved in the selection of an appropriate
fluid. In this exercise we will tend to ignore cardiovascular
changes such as increased venous capacitance.
Certain simplifing assumptions are made in
clinical practice about the sizes of the various fluid
compartments to facilitate the mental arithmetic without loss of
any clinically relevant precision. The water of dense connective
tissue & bone is significant in volume (15% of total body
water) but as a kinetically slow compartment. It is not important
in consideration of short term fluid distribution. Transcellular
fluids are small in volume and usually slow so they too are
excluded from this clinical analysis.
This leaves three big compartments:
Intracellular fluid (55% of
TBW, 23 liters)
• Interstitial fluid (20% of
TBW, 8.4 liters)
Intravascular fluid (Plasma
7.5% of TBW, 3.2 liters and Red cell volume 1.8 liters).
The IVF is the blood volume with 5 liters in
total. The red cell volume is part of the ICF but also is part of
the blood volume. The ratio of ICF to ECF is 23 : 11.6 (about 2 :
1). The ratio of ISF to plasma volume is 8.4 : 3.2 and this will
be treated as about 3 : 1. This discussion only considers those
parts of the total body water that are rapidly equilibrating.
These are the only components that need to be considered in acute
Assumptions used for this Simple Analysis
• TBW is
one-third ECF & two-thirds ICF
• ECF is
one-quarter plasma & three-quarters ISF
threshold of the volume receptors is 7-10% change in
osmoreceptors are sensitive to a 1-2% change in
osmolality is normal prior to the transfusion (ie
Now, consider the rapid IV administration of
1,000 mls of the following fluids: Dextrose
5%, normal saline and plasma protein
solution. The type of questions to be
• How are these different fluids distributed in
How are tonicity and
intravascular volume affected?
What are the mechanisms the
body uses to excrete these fluids?
Which is excreted the most
Dextrose 5% is a ‘Maintenance Fluid’.
(Dextrose is d-glucose). It is isosmotic as administered and
does not cause haemolysis. The glucose is rapidly taken up by
cells. The net effect is of administering pure water, so it is distributed
throughout the total body water. Each compartment receives
fluid in proportion to its contribution to the TBW (ie 2/3rd to
ICF and 1/3rd to ECF; the ECF fluid is distributed one quarte to
plasma & three quarters to ISF).
The distribution of 1,000 mls of dextrose 5%
ECF 330mls (with ISF 250mls
and plasma 80mls).
(The figures are rounded slightly)
Intravascular volume increases from 5000 to
5080 mls. This volume increase of less then 2% which will not be
sensed by the volume receptors (as it is below the 7-10%
The osmolality of plasma (3,200 mls) will
decrease by: [ 287 - (287 x 3.20 / 3.28) ] which is about 7
mOsmoles/l or a 2.5% decrease. This is enough to be detected by
the osmoreceptors. ADH release will be decreased and renal water
excretion will rise. A delay will occur because the changes have
to be detected centrally and then ADH levels need 3 half-lifes
to fall to a new steady state.
Normal saline is an ‘ECF Replacement Fluid’.
Its [Na+] is similar
to that of the extracellular fluid and this effectively limits
its distribution to the ECF (distributing between the ISF
& the plasma in proportion to their volume ie 3:1).
The ISF will increase in volume by 750 mls.
The plasma volume will increase by 250 mls. This is why blood
loss of 1,000 mls requires about 3 to 4 times the volume of IV
replacement fluid to restore normal intravascular volume.
Plasma osmolality and tonicity will be
unchanged because normal saline is isosmotic. The osmoreceptors
do not contribute anything to the excretion of normal saline.
Blood volume increases to 5250 mls; an increase of 5%. This is
below the sensitivity of the volume receptors. It seems that the
body has no clear way of excreting this excess fluid as neither
osmoreceptors nor volume receptors are stimulated! However,
experiments have shown that ‘replacement fluids’ are
excreted the most rapidly of all these groups!
How does this happen? An additional mechanism
is relevant here. Normal saline contains no protein so the
oncotic pressure in the blood is slightly lowered following the
saline infusion. This has 2 effects:
Movement of fluid into the
ISF is favoured (Starling’s Hypothesis)
imbalance occurs: the lowered
oncotic pressure immediately leads to an increase in GFR and a smaller reabsorption of
water in the proximal tubule. Urine flow increases. This is a strictly local effect
without any hormonal intermediary. The urine flow increases immediately. Fluid then moves back into
the intravascular compartment
and the urine flow continues until all the transfused fluid
Plasma Protein Solution
Plasma protein solution is a colloid and is
distributed only to the intravascular fluid. The tonicity is
unaltered. The blood volume increases from 5,000 mls to 6,000
mls; an increase of 20%. This is above the 7 to 10% threshold
for the volume receptors. The result is a fall in ADH levels and
the excretion of the excess water commences.
This water loss tends to increase the plasma
oncotic pressure and water moves from the ISF to the IVF.
Vascular reflexes are important also in causing venous pooling
and a decrease in the ‘effective’ circulating volume. These
mechanisms tend to slow the excretion of the water load. The
albumin is partly slowly redistributed to the ISF and
metabolised. These changes are slow so the effect of plasma
protein infusion on blood volume is both more pronounced and
The pressure-volume control mechanisms
important in long term regulation of blood volume are slow in
onset but become relevant here as the blood volume change is
more significant and more prolonged and occurs without change in
osmolality (or initially in plasma oncotic pressure either).
Dextrose 5% is essentially treated by the
body as pure water and a significant percent moves
intracellularly. It is a useful fluid to replenish intracellular
fluid but does so at the expense of tonicity. It is
inappropriate for intravascular volume replacement. It is
excreted because ADH levels decline in response to the drop in
Normal saline is a ‘replacement fluid’
(meaning ECF replacement) because it adds only to the ECF
volume. Only about a third remains intravascularly. To replace
intravascular volume will require transfusion with about 3 times
the volume of blood lost. It is cheap and readily available. It
is excreted because the small drop in plasma oncotic pressure
causes glomerulotubular imbalance. ADH is not affected.
Plasma protein solutions (eg 5% human albumin) are excellent
for replacing intravascular volume. ISF and ICF will not be
replenished. Albumin is slow to be excreted and the transfused
volume is excreted much slower than with replacement solutions.
Plasma protein solutions are expensive and supply is limited.
The fluid is initially excreted because of a fall in ADH level
falling stimulation of the volume receptors.
All material © Copyright - Kerry Brandis, 2001