Body Fluids 1 and 2

Linda Costanzo, Ph.D.

OBEJCTIVES:

After studying this lecture, the student should understand:

1. The distribution of water between the major body fluid compartments.

2. How to measure the volumes of body fluid compartments using marker
substances.
3. The differences in composition between the major body fluid compartments.
4. The pathophysiology of the major fluid shift examples, including the predicted
changes in osmolarity, ECF and ICF volume, and hematocrit.
5. How to calculate new osmolarity and new ECF and ICF volumes following a
fluid shift.

I. BODY FLUID COMPARTMENTS

Water content (total body water, or TBW) comprises about 60% of body weight.
The percentage varies between 50-70%, depending on gender and amount of
adipose tissue. Males tend to have a higher percentage of water than females.
Water content is inversely correlated with adipose tissue. Infants have up to 75%
body weight as water, which is why severe diarrhea can be life-threatening.

Water is distributed between two major compartments: intracellular fluid (ICF)

and extracellular fluid (ECF), which are separated from each other by cell
membranes. ICF is 2/3 of TBW and ECF is 1/3 of TBW. ECF is further sub-
divided into two compartments, the interstitial fluid and plasma compartments,
which are separated from each other by capillary walls. Interstitial fluid is 3/4 of
ECF, and plasma water is 1/4 of ECF. Lymph, which is part of the ECF, is
interstitial fluid that is collected in the lymphatic vessels and then returned to the
plasma compartment.

An additional minor compartment is the transcellular fluid, which is not part of

ICF or ECF. Transcellular fluids are separated from the rest of the body fluids by
a layer of cells, and they include gastrointestinal, peritoneal, pleural, and
cerebrospinal fluids. Collectively, the volume of transcellular fluids is small, so
they are ignored in the above summary numbers.
Figure 1. Body fluid compartments. Total body water
is distributed between intracellular fluid and
extracellular fluid. Water as a percentage of body
weight is indicated for the major compartments.

A simple tool is the 60-40-20 rule. Approximately 60% of body weight is water
(TBW), 40% of body weight is ICF, and 20% is ECF. (ICF is 2/3 of TBW, i.e.,
40% of body weight; ECF is 1/3 of TBW, i.e., 20% of body weight.)

II. MEASUREMENT OF BODY FLUID COMPARTMENT VOLUMES

The volumes of body fluid compartments are measured with a method based on
the principle of dilution.

A. Method

1. A marker substance is selected, whose physical characteristics

are such that it distributes only in the body fluid compartment
whose volume you wish to calculate. For example, isotopic water
(e.g., D20) distributes throughout the TBW, and thus is a marker
for TBW. Mannitol, a large sugar, distributes throughout the ECF,
but does not cross cell membranes, and thus is a marker for ECF
volume. Radioactively labeled albumin distributes wherever
 albumin is located, and thus is a marker for plasma volume. See
below for list of the marker substances.

2. A known amount of the marker is given. Wait for equilibration,

then measure the concentration of the marker. Correct for any
losses of marker that occurred during the equilibration period (e.g.,
excretion in urine).

3. Knowing the amount present in the body (amount given any minus
loss during equilibration) and the measured concentration,
calculate the volume of distribution of the marker substance (the
volume it was dissolved in). This is the volume of that body fluid
compartment, e.g., volume of distribution of D20 is volume of
TBW, etc.

Volume = amount
concentration

or, more specifically

Volume = amount given - amount lost during equilibration

concentration

B. Marker substances

Direct measurements and their marker substances:

Marker Substances
D20
TBW HT0
Antipyrene
Mannitol
ECF Inulin
Radioactive sulfate
Radioiodinated serum albumin (RISA)
Plasma Evan’s blue (dye that binds to serum
albumin)

Indirect measurements (there is no unique marker substance for these

compartments):

ICF TBW - ECF

Interstitial ECF - plasma
 C. Example

A 70 kg male is injected with 1.5 g of mannitol. During the equilibration

period, 5% of the mannitol was excreted/hour. After two hours of
equilibration, the plasma concentration of mannitol was measured as 9
mg/100 ml. What body fluid compartment is being measured, and what is
its volume (i.e., what is the volume of distribution of mannitol)? Is this a
reasonable number?

Volume = 1500 mg - 150 mg

9 mg/100 ml

= 1350 mg
90 mg/L

= 15 L (volume of distribution of mannitol, or ECF volume)

An ECF volume of 15 L is reasonable for a 70 kg male. (70 kg ≈ 70 L.

20% of 70 L = 14 L......close enough for an approximation.)

III. COMPOSITION OF BODY FLUID COMPARTMENTS

The major difference in composition of body fluid compartments is between ICF

and ECF, which are essentially “mirror images” of each other – what’s high in
concentration in ECF is low in ICF, and vice versa. Transporters in cell
membranes create and maintain most of these differences in composition. There
are also small differences in composition between plasma and interstitial fluid
(which are both ECF); these differences in composition are due to the Gibbs-
Donnan effect of plasma protein, whereby interstitial fluid has a slighter higher
concentration of small anions (e.g., Cl-) and a slighter lower concentration of
small cations (e.g., Na+) than plasma.

Solute Plasma Interstitial Intracellular

Na+, mmol/L 144 140 15
K+, mmol/L 4.8 4.5 120
Ca2+, mmol/L (ionized) 1.3 1.2 10-7M
Cl- , mmol/L 100 109 20
HCO3- , mmol/L 24 25 15
Protein, g/dL 7 ---- 30
Osmolarity, mOsm/L 290 290 290

A few tidbits on units. Please save for reference!

1. Concentrations in body fluids are often expressed in molarity, such as

mmol/L.
 2. For electrolytes, we sometimes use equivalents, such as mEq/L, which
is the concentration in mmol/L x charge on the ion. Thus, for univalent
ions, mEq/L = mmol/L; for divalent ions, mEq/L = 2 x mmol/L. That
is, a Na+ concentration of 1 mmol/L = 1 mEq/L; a Ca2+ concentration
of 1 mmol/L = 2 mEq/L.

3. Osmolarity is total solute concentration, expressed in units of

mOsmoles/liter. Osmolarity is concentration of solute particles, or
concentration in mmol/L x number of particles that dissociate in
solution. The number of particles that dissociate in solution is called
“g,” the osmotic coefficient. For example, the osmolarity of 150
mmol/L NaCl = 150 mmol/L x 2 = 300 mOsm/L (since NaCl
dissociates into two particles in solution, i.e., g = 2). Osmolality is
virtually the same thing as osmolarity, but expressed as mOsmoles/kg
H20. Plasma osmolarity can be approximated
as 2 x [Na+]. I will show you a more precise estimate of plasma
osmolarity in a subsequent lecture.

4. Substances like proteins are conventionally expressed in g/dL, where a

dL (deciliter) is 100 ml and is also called “%.”

a. % can mean “g per 100 ml.” For example, 0.9% NaCl is 0.9 g
NaCl/100 ml. It’s weird, but that’s what it means.
b. mg % means “mg per 100 ml.” For example, 5 mg% KCl
means 5 mg KCl/100 ml.

IV. FLUID SHIFTS - QUALITATIVE

A. Definitions and rules for fluid shifts

1. Osmolarity is the concentration of solute particles, in units of

mOsm/L.

2. Osmolarities of ECF and ICF are always equal in the steady state
(see Table above).

3. H2O shifts freely across cell membranes to establish and maintain

this equality. (This is the “fluid shift” we’ll be talking about.)

4. If a disturbance causes a change in ECF osmolarity, thus producing

a transient difference in ECF and ICF osmolarity, H2O shifts
between ECF and ICF until the osmolarities are equal again; once
the fluid shift has occurred, this is called the new steady state.

5. For purposes of discussion, we assume that NaCl, NaHCO3, and

mannitol are “extracellular” solutes; that is, they are confined to
 ECF because they do not cross cell membranes.

6. Fluid shift disturbances are categorized according to whether they

involve an increase or decrease in ECF volume:

a. Volume contraction means a decrease in ECF volume;

also called volume depletion. Volume contraction causes
decreased blood volume and decreased blood pressure (Pa).
b. Volume expansion means an increase in ECF volume.
Volume expansion can cause increased Pa and edema.

7. Fluid shift disturbances are also categorized according to whether

they cause a change in body fluid osmolarity:

a. Isosmotic means no change in body fluid osmolarity

b. Hyperosmotic means body fluid osmolarity is increased
c. Hyposmotic means body fluid osmolarity is decreased

B. Method for analyzing fluid shift problems – do it this way every time!

1. Read the problem or case scenario and determine clearly what was
gained or lost. For example, if a person eats dry NaCl, then NaCl
was gained. If a person sweats profusely on a hot day, then NaCl
and water were lost.

2. Assume that any gain or loss from the body affects the ECF first.

3. Predict whether the gain or loss would cause a change in ECF

osmolarity. For example, if a person eats dry NaCl, then NaCl is
added to ECF and causes an increase in ECF osmolarity.

4. If there is a predicted change in ECF osmolarity, determine which

way water must shift to make the ECF and ICF osmolarities equal
again.

5. Finally from your analysis above, predict the directional changes in

the new steady state (after any fluid shift has occurred) for: ECF
and ICF osmolarities, ICF volume, ECF volume, and TBW. Also
predict whether there will be a change in hematocrit and plasma
protein concentration. (Reminder: hematocrit is the fractional
blood volume occupied by red blood cells [RBCs].)

C. Examples (see following table and figure)

1. Loss of isosmotic NaCl (isosmotic volume contraction) – e.g.,

diarrhea. A person who has diarrhea loses isosmotic (and isotonic)
 fluid from the GI tract. The loss causes no change in ECF
osmolarity since the fluid lost has the same osmolarity as the body
fluids. Since there is no change in ECF osmolarity, no fluid shift is
required. Thus, in the new steady state, ECF and ICF osmolarities
are unchanged, ECF volume is decreased (due to the loss of
isosmotic fluid, and ICF volume is unchanged. TBW is decreased
because ECF volume is decreased. In considering the effects of the
disturbance on plasma protein concentration and hematocrit,
remember that plasma is part of ECF; if ECF volume decreases,
then plasma volume also decreases. Plasma protein concentration
is increased by a concentrating effect (the fluid lost in diarrhea
does not contain plasma proteins). Hematocrit is also increased by
a concentrating effect, because the same number of RBCs are
“dissolved” in a smaller plasma volume.

2. Loss of water (hyperosmotic volume contraction) – e.g. water

deprivation and diabetes insipidus (lack of ADH, antidiuretic
hormone). For example, a person with a high fever loses
“insensible” water. If this water is not replaced, there will be an
increase in ECF osmolarity (water is lost from ECF, solute is left
behind and becomes concentrated). Thus, transiently, ECF
osmolarity is higher than ICF osmolarity. The body will not permit
this inequality, and water shifts from ICF into ECF until ECF and
ICF osmolarities are again equal, and both higher than normal. In
the new steady state, ECF and ICF osmolarities are increased. ECF
volume is decreased (because of the initial loss of water). ICF
volume is decreased (because of the water shift). TBW is
decreased. Plasma protein concentration is increased (because the
loss of ECF volume concentrates the plasma proteins). Hematocrit,
it seems, would also be increased. However, hematocrit is
unchanged because of two offsetting effects. (1) The loss of ECF
and plasma volume “concentrates” the RBCs (same number of
RBCs in a smaller volume), which tends to increase hematocrit. (2)
RBCs are cells. In this example, there is a water shift out of cells,
causing the RBCs to shrink, and therefore occupy a smaller
fractional volume, which tends to decrease hematocrit.

3. Loss of NaCl (hyposmotic volume contraction) – e.g, adrenal

insufficiency. In adrenal insufficiency, there is lack of aldosterone,
the hormone that promotes renal Na+ reabsorption. When
aldosterone is lacking, there is excess urinary excretion of NaCl
and net loss of NaCl from the body. When NaCl is lost from ECF,
there is a decrease in ECF osmolarity. Thus, transiently, ECF
osmolarity is lower than ICF osmolarity. Water shifts from ECF to
 ICF until the osmolarities are equal again, and both lower than
normal. In the new steady state, ECF and ICF osmolarities are
decreased. ECF volume is decreased (due to the water shift), ICF
volume is increased (due to the water shift), and TBW is
unchanged. Plasma protein concentration is increased due to
concentration of plasma proteins. Hematocrit is increased both due
to “concentration” of RBCs and due to the shift of water into RBCs
(causing them to swell).

4. Gain of isosmotic NaCl (isosmotic volume expansion) -- e.g.,

infusion of isosmotic saline. A person is infused with an isotonic
(and isosmotic) saline (NaCl) solution. The infusion would cause
no change in ECF osmolarity, since the infused solution has the
same osmolarity as the body fluids. Since there is no change in
ECF osmolarity, no fluid shift is required. Thus, in the new steady
state, ECF and ICF osmolarities are unchanged, ECF volume is
increased (due to the addition of the infused solution, and ICF
volume is unchanged. TBW is increased because ECF volume is
increased. Plasma protein concentration is decreased by dilution
(the infused solution contained no protein). Hematocrit is also
decreased because the same number of RBCs are “dissolved” in a
larger volume.

5. Gain of NaCl (hyperosmotic volume expansion) – e.g., high NaCl

intake. NaCl is added to ECF, and there is an increase in ECF
osmolarity. Thus, transiently, ECF osmolarity is higher than ICF
osmolarity. Water shifts from ICF to ECF until the osmolarities are
equal again, and both higher than normal. In the new steady state,
ECF and ICF osmolarities are increased. ECF volume is increased
(due to the water shift), ICF volume is decreased (due to the water
shift), and TBW is unchanged. Plasma protein concentration is
decreased due to dilution of plasma proteins. Hematocrit is
decreased both due to “dilution” of RBCs and due to the shift of
water out of RBCs (causing them to shrink).

6. Gain of water (hyposmotic volume expansion) – e.g., excess

water-drinking and SIADH (syndrome of inappropriate ADH).
Water is first added to ECF and there is a decrease in ECF
osmolarity. Transiently, ECF osmolarity is lower than ICF
osmolarity. The body will not permit this inequality, and water
shifts from ECF into ICF until ECF and ICF osmolarities are again
equal, and both lower than normal. In the new steady state, ECF
and ICF osmolarities are decreased. ECF volume is increased
(because of the initial addition of water). ICF volume is increased
 (because of the water shift). TBW is increased. Plasma protein
concentration is decreased (because the increased ECF volume
dilutes plasma proteins). Hematocrit, it seems, would also be
decreased. However, hematocrit is unchanged because of two
offsetting effects. (1) The increase in ECF and plasma volume
“dilutes” the RBCs (same number of RBCs in a larger volume),
which tends to decrease hematocrit. (2) RBCs are cells, and in this
example, there is a water shift into cells, causing the RBCs to
swell, and therefore occupy a larger fractional volume, which tends
to increase hematocrit.

Disturbances of Body Fluids

ECF ICF Plasma
Type Example Osmolarity Hematocrit
Volume Volume [protein]
Isosmotic volume
contraction
Diarrhea ↓ N.C. N.C. ↑ ↑
Sweating;
Hyperosmotic volume
contraction
fever; diabetes ↓ ↓ ↑ N.C. ↑
insipidus
Hyposmotic volume Adrenal
contraction insufficiency
↓ ↑ ↓ ↑ ↑
Isosmotic volume Infusion of
expansion isotonic NaCl
↑ N.C. N.C. ↓ ↓
Hyperosmotic volume High NaCl
expansion intake
↑ ↓ ↑ ↓ ↓
Hyposmotic volume
expansion
SIADH ↑ ↑ ↓ N.C. ↓
ECF, Extracellular fluid; ICF, intracellular fluid; NaCl, sodium chloride; N.C., no change; SIADH syndrome
of inappropriate antidiuretic hormone.
Figure 2. Shifts of water between body fluid compartments. Normal extracellular fluid
(ECF) and intracellular fluid (ICF) osmolarity are shown by solid lines. Changes in volume
and osmolarity in response to various disturbances are shown by dashed lines. SIADH,
Syndrome of inappropriate antidiuretic hormone.

V. FLUID SHIFTS - QUANTITATIVE

A. How to analyze and calculate. Fluid shift problems can also be analyzed
quantitatively. That is, in addition to the qualitative approach above (e.g.,
whether osmolarity is increased or decreased, and whether ECF volume is
increased or decreased), we also can calculate the exact values for new
steady state osmolarity and body fluid volumes. That’s what I mean by
“quantitative.” To work these problems correctly and reliably, you must
perform the following steps in the following order. In the next section of
Examples, you will see how to work problems using these steps.

1. First, determine clearly what was gained or lost in the problem.

From the case scenario, calculate the number of osmoles
(mosmoles) gained or lost and the volume (L) gained or lost.
2. Next, calculate the new osmolarity of TBW in the new steady state.
We do this step next because we know that the new steady state
osmolarity will be the same throughout the body fluid
 compartments (TBW). The calculated value of TBW osmolarity
will be the value for ECF and ICF osmolarities used in Step 3.
3. Finally, using the new, calculated TBW osmolarity (per Step 2),
calculate the new ECF and ICF volumes.

B. Examples

1. A man with a TBW of 40 L, ICF volume of 26.4 L, ECF volume of

13.6 L, and plasma osmolarity of 290 mOsm/L drinks 3 L of water.
In the new steady state, what is his plasma osmolarity, TBW, ECF
volume, and ICF volume?

What was gained or lost?

Gain = 3 L of water

New TBW osmolarity?

Old TBW osmoles = 40 L x 290 mOsm/L = 11,600 mOsm
New TBW = 40 L + 3 L = 43 L
11,600 mosmoles/43 L = 269.8
New TBW osmolarity =
mOsm/L

New ECF volume?

Old ECF osmoles = 13.6 L x 290 mOsmles/L
= 3944 mOsm
New ECF volume = 3944 mosmoles/ 269.8 mOsm/L
= 14.6 L

New ICF volume?

Old ICF osmoles = 26.4 L x 290 mOsm/L
= 7656 mOsm
New ICF volume = 7656 mOsm/269.8 mOsm/L
= 28.4 L

2. A woman with an ICF volume of 28 L, ECF volume of 14 L, and

plasma osmolarity of 295 mOsm/L, eats a bag of potato chips that
contains 300 mmoles of NaCl. Assuming that the osmotic
coefficient of NaCl is 2, in the new steady state, what is her plasma
osmolarity, TBW, ECF volume and ICF volume? How much water
shifted, and in which direction?

What was gained or lost?

Gain = 300 mmoles of NaCl
= 600 mosmoles (300 x 2)
 New TBW osmolarity?
Old TBW = 28 L + 14 L
= 42 L
Old TBW osmoles = 42 L x 295 mOsm/L
= 12,390 mOsm
New TBW osmoles = 12,390 mOsm + 600 mOsm
= 12,990 mOsm
New TBW osmolarity= 12,990 mOsm/42L
= 309.3 mOsm/L

New ECF volume?

Old ECF osmoles = 14 L x 295 mOsm/L
= 4130 mOsm
New ECF osmoles = 4130 mOsm + 600 mOsm
= 4730 mOsm
New ECF volume = 4730 mOsm/309.3 mOsm/L
= 15.3 L

New ICF volume?

Old ICF osmoles = 28 L x 295 mOsm/L
= 8260 mOsm
New ICF volume = 8260 mOsm/309.3 mOsm/L
= 26.7 L

How much water shifted, and in what direction?

1.3 L, from ICF to ECF

3. A man with a TBW of 40 L, ECF volume of 13 L, ICF volume of

27 L, and plasma osmolarity of 300 mOsm/L is infused with 2 L of
a solution of 0.45% NaCl. After the infusion, in the new steady
state, what is his plasma osmolarity, ECF volume, and ICF
volume? (For NaCl, assume molecular weight is 58 g/m and
osmotic coefficient is 2.0.)

What was gained or lost?

2 L of 0.45% NaCl
0.45 g/100 ml x 2000 ml ÷ 58
= 0.155 moles
g/mole
0.155 moles x 2 = 0.310 osmoles
= 310 mosmoles

Gain = 310 mosmoles

and
2L
 New TBW osmolarity?
Old TBW osmoles = 40 L x 300 mOsm/L
= 12,000 mOsm
New TBW osmoles = 12,000 mOsm + 310 mOsm
= 12,310 mOsm
New TBW osmolarity= 12,310 mOsm/42 L
= 293 mOsm/L

New ECF volume?

Old ECF osmoles = 13 L x 300 mOsm/L
= 3900 mOsm
New ECF osmoles = 3900 mOsm + 310 mOsm
= 4210 mOsm
New ECF volume = 4210 mOsm/293 mOsm/L
= 14.4 L

New ICF volume?

Old ICF osmoles = 27 L x 300 mOsm/L
= 8100 mOsm
New ICF volume = 8100 mOsm/293 mOsm/L
= 27.6 L

VI. PRACTICE QUESTIONS

1. Woman with ECF volume= 15 L, ICF volume =25 L, and plasma

osmolarity = 300 mOsm/L runs a marathon on a hot day. She loses 3 L of
sweat that has an osmolarity of 200 mOsm/L, and replaces all volume lost
by drinking pure water.

Her plasma osmolarity in new steady state?

New ECF volume?
New ICF volume?
New TBW?
Hct inc, dec, or unchanged?
New plasma Na concentration (inc, dec, or unchanged)?

2. Man with TBW= 45L, ECF volume=17L, and plasma osmolarity= 300
mOsm/L eats some yummy Sunchips (original) containing 450 mOsmoles
of NaCl. Being on a tight budget, he washes them down with 1.5 L of
water.

New osmolarity?
 Direction of water shift?
Plasma protein inc, dec, or unchanged?
Hct inc, dec, or unchanged?
New plasma Na concentration (inc, dec, or unchanged)?

3. Woman has TBW=42 L, ECF volume = 15 L, ICF volume=27 L, and

plasma osmolarity=290 mOsm/L. She develops an infection with high
fever and loses 2 L of water in insensible losses. She is unable to drink or
eat.

New plasma osmolarity?

Approximate (value) new plasma Na concentration?
New TBW?
New ICF volume?

4. A man is injected with 2000 :Ci of tritiated water (HTO) and 4000 mg of
inulin. After equilibration, a plasma sample had an HTO concentration of
4 :Ci/100 ml and an inulin concentration of 16 mg/100 ml. During
equilibration, 20% of the inulin injected was excreted in the urine, and 2%
of the HTO injected was excreted. What are the man’s TBW, ECF, and
ICF volumes?

VII. ANSWERS

For Questions 1-3, I intentionally gave numerical answers or directional changes

without the step-by-step solutions. That way, if you get it wrong, you can try
again without having seen clues in the solution – you’ll learn better that way. If
you’re stumped, come by and see me.

1. Her plasma osmolarity in new steady state? 285 mOsm/L

New ECF volume? 13.68 L
New ICF volume? 26.32 L
New TBW? 40 L
Hct inc, dec, or unchanged? Inc
New plasma Na concentration? Dec

2. New osmolarity? 300 mOsm/L

Direction of water shift? None
Plasma protein inc, dec, or unchanged? Dec
Hct inc, dec, or unchanged? Dec
New plasma Na concentration? No change
3. New plasma osmolarity? 304.5 mOsm/L
Approximate new plasma Na concentration? Approx 152 mEq/L
New TBW? 40 L
New ICF volume? 25.7 L

4. TBW = 2000 :Ci - 40 :Ci

4 :Ci/100 ml
= 49 L

ECF = 4000 mg - 800 mg

16 mg/100 ml
= 20 L

ICF = TBW - ECF

= 49 L - 20 L
= 29 L