BODY FLUID COMPARTMENTS GIBBS-DONNAN EFFECT
• The precise amount of water depends on a
person’s body composition.
• Fat doesn’t store any water = person’s water
content is inversely proportional to a person’s
fat content.
− Muscular and lean person would have a
relatively high proportion of their body
weight made up of water.
− Additionally, females tend to have more fat
than males and so on average tend to have
lower proportion of their body weight made
up of water.
INTRACELLULAR
• Intracellular fluid is important for dissolving
cations (positive charge), and anions (negative
charge)
−2 major intracellular cations: potassium
(K ) and magnesium (Mg2+)
+ − For example, Na+K+ ATPases help to
− 2 major intracellular anions: proteins and
organic phosphates like ATP.
• Principle of Macroscopic Electroneutrality:
Fluid compartments always maintain the same
concentration of positive charges as negative
ones in order to stay electrically neutral
− Example: K in the intracellular fluid is
+ body fluid compartments.
balanced out by negatively charged proteins
and organic phosphates.
EXTRACELLULAR FLUID
• Subdivided into interstitial fluid and plasma
(both are really similar)
− Interstitial fluid: found surrounding the cell
− Plasma: aqueous portion of blood.
• Major cation: Sodium (Na+)
• 2 major anions: Chloride (Cl-) & Bicarbonate
• Plasma – 55% of the blood (remaining 45% is
mostly made of RBCs, WBCs and platelets)
− Plasma is made up of around 90% water and
10% proteins like albumin which help
transport hormones and minerals.
− Plasma leaks out of the blood and goes into
the interstitium (space between cells)
through tiny pores between endothelial cells
in the capillaries. These tiny pores between
capillaries lets small solutes and water to
pass through but block large proteins and
cells.
• Some proteins are too large to pass into the
interstitium, a phenomenon called the Gibbs-
Donnan effect helps the plasma remain
electrically neutral.
• Occurs when the abundance or negatively
charged large proteins repels smaller anions
into the interstitium while attracting small
cations into the plasma.
− So compared to the plasma, interstitial fluid
tends to have higher concentrations of small
anions like Cl- and lower concentrations of
small cations like Na+
Plasma and Interstitial Fluid
• Difference between plasma and interstitial fluid
is small, whereas the difference between
intracellular fluid and extracellular fluid is quite
large and physiologically important.
establish a high concentration of K+ inside
the cell and a high concentration of Na+
outside the cell.
DILUTION METHOD
• Used for measuring the volume of each of the
• Various substances which settle in a specific
fluid compartment are given to an individual
and their concentration is measured.
− Plasma – radiolabeled albumin: Albumin is
a large protein that cannot move into the
interstitial space.
− Interstitialcompartment – mannitol and
inulin (slightly smaller molecules): It can
pass through the capillaries into the
interstitium but cannot cross the cell
membrane.
− Intracellular compartment – Heavy water
isotopes (D2O) (molecules that can freely
diffuse across the cell membrane): to be
easily differentiated from normal water, or
H2O, that’s in the body.
▪ Once adsorbed, D2O will act just like
water and distribute in the 60-40-20
fashion, so 2/3s of it is intracellular and
⅓ is extracellular.
• By injecting a known amount of the substance
and allowing the substance to diffuse through
the fluid compartments, it’s possible to measure
 the concentration of that substance in the
blood, as well as if any was lost in the urine.
• Calculate the volume of distribution via the
equation:
𝑨𝒎𝒐𝒖𝒏𝒕
𝑽𝒐𝒍𝒖𝒎𝒆 =
𝑪𝒐𝒏𝒄𝒆𝒏𝒕𝒓𝒂𝒕𝒊𝒐𝒏
Sample Problem
SUMMARY
• A 70-kg man is injected with 150 mCi
(millicurie), of D2O and 650 mg of mannitol.
During a 2-hour equilibration period, he
excretes 10% of the D2O and 10% of the
mannitol in his urine. After that, the
concentration of D2O in plasma is 0.32 mCi/100
mL and the concentration of mannitol is 4.6
mg/100 mL.
• Given:
▪ Amounts: 150 mCi (D2O) and 650 mg
(mannitol)
▪ Concentrations: 0.32 mCi/100 mL (D2O) 4.6
mg/100 mL (mannitol)
SAMPLE QUESTIONS
• Solutions:
• For the volume Total body water
▪ 150 mCi – 15 mCi = 135 mCi [Total
Amount]
▪ 𝐕𝐨𝐥𝐮𝐦𝐞 = 𝟎.𝟑𝟐 𝟏𝟑𝟓 𝐦𝐂𝐢
= 𝟒𝟐. 𝟐 𝐋
𝐦𝐂𝐢 / 𝟏𝟎𝟎𝐦𝐋
• Explanation:
− To figure out the volume of total body
water, we look at D2O which will settle in the
extracellular and intracellular fluid
compartments.
− Subtract out the amount of D2O excreted
(which is 10% of the inject amount) from the
total amount (150 mCi)
− Then we divide that amount by the
concentration of 0.32 mCi/100 mL, which
gives us the volume of 42.2 Liters.
• For the volume of Extracellular Fluid
▪ 650 mg – 6.5 mg = 643.5 mg [Total
amount]
𝟔𝟒𝟑.𝟓 𝐦𝐠
▪ 𝐕𝐨𝐥𝐮𝐦𝐞 = 𝟒.𝟔𝐦𝐠 / 𝟏𝟎𝟎 𝐦𝐋
= 𝟏𝟐. 𝟕 𝐋
• Explanation:
− Extracellular fluid volume equals the amount
of mannitol injected, minus the amount of
mannitol excreted (10% of the injected),
divided by the concentration of mannitol
• For the volume of Intracellular Fluid
▪ 42.2 L – 12.7 L = 29.5 L
• Explanation:
− Intracellular fluid volume which cannot be
measured directly, we need to take the
difference between the total body water and
the extracellular fluid volume.
• 60-40-20 rule states that total body water takes
up about 60% of our body weight, and more
specifically, 40% is intracellular fluid, and 20% is
extracellular fluid.
• Measurements of these fluid compartments
uses the dilution method where various
substances are injected and allowed to
distribute differently among these fluid
compartments.
• Final concentrations from plasma are taken to
calculate the volume of fluid compartments.
• Approximately two-thirds of body water by
volume is contained in the intracellular fluid
compartment.
• Approximately one-third of body water by
volume is contained in the extracellular fluid
compartment.
• Approximately 40% of body weight is in the
intracellular fluid compartment.
• Approximately 20% of body weight is in the
extracellular fluid compartment.
• The extracellular fluid compartment of the body
is divided into plasma and interstitial fluid.
• Interstitial fluid is the fluid in microscopic
spaces between cells.
• Of the one-third of body water in the
extracellular fluid compartment, approximately
20% is found in the plasma.
• Exchange of fluid from plasma to the interstitial
fluid occurs across capillary walls.
• Women typically have a lower percentage of
body water.
• Generally speaking, obese individuals will have
a lower percentage of body weight as water.
• The major cations in the intracellular fluid are
potassium and magnesium.
• The major cation of the extracellular fluid is
sodium.
 • The major anions of the extracellular fluid are
chloride and bicarbonate.
• The major anions of the intracellular fluid are
proteins and organic phosphates like ATP and
ADP.
• A large molecular weight protein or sugar like
mannitol or inulin would be distributed only to
the extracellular compartments.
• Isotopic water, like D2O or tritiated water, are
used as markers for total body water.
• A 70 kg man is administered inulin. Because it
is freely filtered and not secreted or reabsorbed,
inulin offers an accurate calculation of GFR.
Inulin would be found in what amount of this
patient's body water? 14L
− Explanation: Inulin is found in the
extracellular fluid and can be used to
measure extracellular fluid volume. To
answer this question, it easiest to divide 70
by 10, which tells us that 10% of her body
weight is 7 kg. Multiplying this value by 2
would give us 20% of body weight, or 14 kg,
which is equivalent to 14 L of water.
MOVEMENT OF WATER BETWEEN BODY
COMPARTMENTS
WATER (60-40-20 rule)
• Water is the key to life - universal solvent
• Total body water: 60% of body weight (BW).
• 2 Major Compartment:
− Intracellular fluid (ICF): (⅔) TBW or 40% BW
− Extracellular fluid (ECF): (⅓) TBW or 20% BW
EXTRACELLULAR FLUID
• Fluid outside the cell which is subdivided into:
− Interstitial fluid: fluid surrounding the cell
− Plasma: fluid that circulates within blood
vessels.
• It is the 1ST to be lost and makes up fluids like
gut fluids, sweat and other secretions.
• Made up of different solutes:
− Sodium (Na+): major cation
− Chloride (Cl-): 1st major anions
− Bicarbonate (HCO3-): 2nd major anions
OSMOLARITY (mOsm/L)
• Measures the specific solute concentration in
each compartment (individual ions within a
solution)
• Osmolarity is also the number of osmoles within
a liter of solution
− Example: NaCl splits apart in H2O to
become Na+ and Cl-, so a solution of 1
mmol/L of NaCl is actually 2 mOsm/L (2
kinds of solute, Na and Cl)
• Normally, osmolarity in the intracellular fluid
and extracellular fluid is equal.
• Osmosis: Process of maintaining the balance
within the intra and extracellular fluid. If either
side ever has a few more solutes, than water will
flow in that direction to lower the concentration
slightly and maintain the balance.
• Some solutes like NaHCO3 (sodium
bicarbonate) and large sugars like mannitol,
are too large to cross cellular membranes and
they’re basically trapped in the ECF.
• Usually, the ECF is more easily affected by
physiologic processes, so we’ll look at the
volume and concentration of the ECF.
− In terms of volume:
▪ Contraction = ECF volume
▪ Expansion =  ECF volume.
− In terms of concentration:
▪ Isosmotic disturbance means that
there’s NO change in ECF osmolarity
▪ Hyperosmotic disturbance: ECF
osmolarity
▪ Hypoosmotic disturbance: ECF
osmolarity.
SCENARIOS
• 6 common scenarios to see how they affect the
body’s fluid compartments
• 2 step approaches:
− 1st:Identify any changes in the ECF
osmolarity
▪ Adding or removing solutes
▪ Gaining or losing water
− 2nd: Water Shift: If there is a change in ECF
osmolarity, we’ll figure out how water must
shift to re-establish balance between ECF
and ICF osmolarity.
1ST: DIARRHEA
• Someone with diarrhea will lose a lot of fluid
and solutes from the gastrointestinal tract which
ultimately comes from the ECF. And the
osmolarity of diarrhea is similar to that of the
ECF.
• Losing fluid in the form of diarrhea:  ECF fluid
• ECF Osmolarity: unchanged
− With no change in osmolarity, there will be
no water shift and ICF volume stays the
same.
− This means that there’s an isosmotic
volume contraction.
• Consequences:  plasma volume leading to:
−  arterial pressure
−  plasma protein concentration
−  hematocrit: portion of blood that’s
occupied by red blood cells
2ND: RUNNING IN MARATHON
• Person running a marathon and losing a ton of
sweat which contains both Na+ and Cl- ions and
water.
• Sweat is actually hypoosmotic relative to ECF so
it contains relatively more water than solute.
• Hyposmotic fluid is lost: ECF volume
• ECF Osmolarity: 
− When the osmolarity in the ECF rises
compared to ICF, water moves by osmosis
from the ICF → ECF.
− Once steady state is established: BOTH
compartments will have
▪ Volume: 
▪ Osmolarity: 
− Thismeans that there’s a hyperosmotic
volume contraction.
• Consequences:
−  plasma protein concentration (due to loss
of volume)
− Unchanged hematocrit (since the RBCs lose
volume as well)
3RD: ADRENAL INSUFFICIENCY
• Deficiency in several hormones including
aldosterone.
− Aldosterone plays a big role in Na+
reabsorption in the kidneys, so in adrenal
insufficiency, excess Na+ is lost in the
urine.
• ECF Osmolarity:  since Na+, a major
component of ECF is lost
− This causes water to shift from the ECF → ICF
by osmosis until both compartments have
the same osmolarity.
− Once steady state is established:
▪ BOTH ECF and ICF osmolarities: 
▪ ECF volume: 
▪ ICF volume: 
− This means that there’s a hypoosmotic
volume contraction.
• Consequences:
−  plasma protein concentration
− hematocrit (due to loss of volume but also
because water will also shift into the red
blood cells)
4TH: INFUSION OF ISOTONIC NaCl
• Person in the hospital getting an infusion of
isotonic NaCl, perhaps after a bout of intense
diarrhea.
− Na+ may leak across the cell membrane and
pass from the ECF into the ICF but the Na/K
ATPase pump actively pushes Na+ into the
ECF and K+ into the ICF.
− Chlorideon the other hand stays around
sodium so that the charges are balanced.
− So ultimately, all of the isotonic NaCl
solution gets added only to the ECF.
• ECF Volume: 
• ECF Osmolarity: Doesn’t change
− Since the solution added is isotonic, it does
not change the osmolarity so there will be
no water shift.
− This means that there’s an isosmotic
volume expansion
• Consequences:
−  plasma protein concentration
− hematocrit (due to dilution)
5TH: EATING SALTY FOODS
• Someone who eats a bag full of salty chips. The
extra Na+ and Cl- ions in the body.
• ECF Volume: Unchanged
• ECF Osmolarity: 
 − This causes water to move from the ICF → SAMPLE QUESTIONS
ECF in order to raise osmolarity in the ICF.
− Once steady state is reached
▪ BOTH ECF and ICF osmolarities: 
▪ ECF volume: 
▪ ICF volume: 
− This means that there’s a hyperosmotic
volume expansion.
• Consequences:
−  plasma protein concentration
−  hematocrit (due to  ECF volume)
▪ Additionally, hematocrit will be further
decreased () from the water shift
out of the red blood cells.
6TH: SYNDROME OF INAPPROPRIATE
ANTIDIURETIC HORMONE (SIADH)
• In this condition, inappropriately high levels of
antidiuretic hormone is released causing the
kidney to increase water reabsorption.
− When there are abnormally high levels of
ADH, too much water is reabsorbed and the
excess water is distributed throughout the
total body water in a 1/3 ECF to 2/3 ICF ratio.
• ECF and ICF volume: 
• ECF and ICF osmolarities: 
• This means that there’s a hypoosmotic volume
expansion.
• Consequences:
− plasma protein concentration (due to
dilution)
− NO change in hematocrit (due to the
concentration of the red blood cells  from
dilution but red blood cell volume 
because water has moved into them)
SUMMARY
• Total body water can be broken down into 1/3
ECF and 2/3 ICF.
• Changes in solutes or water volume in these
compartments causes a compensatory reaction
where water flows in order to balance out both
compartments until they have the same
osmolarity and reach a new steady state.
• As a consequence of water shifts, both plasma
protein concentration and hematocrit will be
affected.
• The volume of a body fluid compartment
depends on the amount of solute contained.
• The normal osmolarity of body fluids is 290
milliosmoles/liter (mOsm/L).
• Intracellular osmolarity is equal to extracellular
osmolarity in the steady state.
• NaCl, NaHCO3, and mannitol are generally
assumed to be confined in the extracellular
fluid compartment(s).
• Volume contraction describes a decrease in
extracellular fluid volume.
• The terms hyperosmotic, hypoosmotic, and
isosmotic refer to the osmolarity of the
extracellular fluid.
• Iso-osmotic volume contraction like diarrhea
and burns can cause a relatively greater volume
decrease in the extracellular fluid
compartment(s).
• Hypo-osmotic volume contraction, like
adrenal insufficiency, can cause a relatively
greater volume decrease in the extracellular
fluid compartment(s).
• Hypo-osmotic volume contraction, like adrenal
insufficiency, can cause a relatively greater
increased volume in the intracellular fluid
compartment(s).
• Hyperosmotic volume contraction, like
sweating, fever, or diabetes insipidus, can
decrease the volume in the extracellular and
intracellular fluid compartment(s).
• Infusion of isotonic saline results in a relatively
greater volume increase of the extracellular
fluid compartment.
• Hypo-osmotic volume expansion, e.g.,
syndrome of inappropriate antidiuretic
hormone, results in increased volume of the
intracellular and extracellular fluid
compartment(s).
• Hyperosmotic volume expansion, e.g., excess
intake of hypertonic saline, results in a relatively
greater volume decrease in the intracellular
fluid compartment.
• Hyperosmotic volume expansion, e.g., excess
intake of sodium chloride, results in relatively
greater increased volume in the extracellular
fluid compartment.
• Sweat is hyposmotic relative to extracellular
fluid.
 Consequences
Scenarios Plasma Protein
Arterial Pressure Hematocrit
Concentration
Diarrhea   

Running in Marathon  Unchanged

Adrenal Insufficiency  
Infusion with Isotonic
 
NaCl
Eating of Salty Food  

SIADH  No change