Robert W. Baer, Ph.D.

March 4-5, 1996

BODY FLUID COMPARTMENTS

General Goal: To describe the major body fluid compartments, and the general processes involved in
movement of water between extracellular and intracellular compartments.
Specific Educational Objectives: The student should be able to:
1. describe what is meant by calling the body an open system, and the influence this has on body
homeostasis.

2. list the major sources of water and the major routes of water loss.

3. be able to express and manipulate solute concentrations in various units including percentage (w/v),
molarity, equivalents, and osmolarity.

4. state the approximate total body water and state the approximate distribution of volume between the
various intracellular and extracellular body compartments.

5. describe influence of the Gibbs-Donnan membrane equilibrium on solute distribution.

6. calculate the size of the various fluid compartments from volume of distribution data for tracer
compounds.

7. state the meaning of the terms isotonic, hypotonic, and hypertonic.

8. calculate the changes in intracellular volume, extracellular volume, plasma osmolarity, and plasma
sodium expected with infusion of various intravenous solutions.

9. describe the difference between “measured osmolarity” and “effective osmolarity”, be able to define
“osmolar gap”, and determine if one is present.

Resources:
Lecture: Dr. Baer
Reading: Guyton, A.C. and J.E. Hall. Textbook of Medical Physiology (9th ed.). W.B. Saunders, 1996.
Chapter 1, Chapter 25, pp. 297-308.
Johnson, L. R. Essential Medical Physiology. Raven Press, 1992. Chapter 1.
Page 2 Body Fluid Compartments

I. THE BODY AS AN OPEN SYSTEM

A. Homeostasis. The process through which bodily equilibrium is maintained. The body is
designed to maintain a constant “internal milieu” with regard to body fluid composition,
temperature, blood pressure, blood glucose level, etc.

B. “Open System”. The body exchanges material and energy with its surroundings.

Figure 1

C. Water Steady State. The amount of water coming into the body each day must equal
the amount of water eliminated from the body over the same period of time. If not, the
body will have either a net water gain or a net water loss.

1. Water Sources:
a) Water Drinking.
b) Water contained in Food.
c) Metabolism to CO2 and H2O.

2. Water Losses:
a) Urinary loss.
b) Fecal loss.
c) Insensible H2O loss. Evaporation from the respiratory tract and the skin
surface (not including sweat which is sensible since it has a purpose).
d) Sweat Losses. At normal room temperature, sweating accounts for
about 25% of heat losses. In cold environments, H2O losses in sweat
decrease. In warm environments, or with exercise, sweat losses increase.
e) Pathological losses. Include: vascular bleeding, vomiting, diarrhea.

D. Electrolyte Steady State. Like H2O, we must consume and eliminate equal quantities of
electrolytes such as sodium (Na+) and potassium (K+).

1. Na+ and K+ normally enter the body mainly by ingestion in food.

2. Clinically, electrolytes also can enter the body parenterally, eg. when a physician
administers an intravenous (i.v.) solution.

3. Electrolyte losses
a) Renal excretion.
b) Stool losses
c) Sweating
 Body Fluid Compartments Page 3

d) Abnormal routes: eg. vomit and diarrhea.

E. Metabolized Substances. Substances which are chemically altered must also be in

balance, but the amount ingested will not have a simple one to one relationship to the
amount eliminated. Balance sheets for this type of substance must be kept in terms of
chemical conservation between substrates and end products.

F. Distribution of various substances within the body is NOT HOMOGENEOUS.

G. Compartment. A non-specific term to refer to a region in the body with a unique

chemical composition or a unique behavior. Compartments are frequently spatially
dispersed, and all the parts of a compartment need not be in contact with each other.

H. Compartments are usually separated from each other either by membranes or by whole
cells forming an epithelial (or endothelial) lining.

II. EXPRESSING FLUID COMPOSITION

A. Gram Molecular Weight (GMW). The number of grams of a substance it takes to

provide a mole (mol) of that substance (i.e., 6.02x1023 molecules). The gram molecular
weight of a molecule can be calculated by summing the atomic weight of its individual
atoms.
T a b le 1
ATOMIC Gram Molecular MOLECULE Gram Molecular
SUBSTANCE Weight (g/mol) Weight (g/mol)

Sodium (Na) 22.99 Bicarbonate ( HCO3- ) 61.02

Potassium (K) 39.10 Phosphate, monobasic 96.99

( H2PO4- )

Calcium (Ca ) 40.08 Phosphate, dibasic 95.98

(HPO42- )

Magnesium (Mg) 24.31 Phosphate (PO43- ) 94.97

Chlorine (Cl) 35.45 Ammonia ( NH3) 17.03

Phosphorous (P) 30.97 Ammonium ( NH4+ ) 18.04

Carbon © 12.01 Glucose ( C6H12O6 ) 180.16

Hydrogen (H) 1.008 Urea ( H2NCONH2) 60.06

Oxygen (O) 16.00 B.U.N. ( N2 ) 28.02

Nitrogen (N) 14.01

Page 4 Body Fluid Compartments

B. Percent Solution Concentrations. Water is the most common solvent. Under standard
conditions 1 ml of water weighs 1 g. Solutions are commonly expressed as
weight/volume (w/v) percentages, that is, solute weight divided by solvent volume (H2O)
times 100. Occasionally, solutions are expressed as weight/weight percentages (w/w)

C. Clinical chemistries generally deal with mg quantities and are reported as mg percentages
or mg/dl.

D. Molality. Concentration expressed as moles solute per kg of solvent.

E. Molarity (M). Concentration expressed as moles solute per liter of solution. Note that
the symbol “M” does not mean moles but rather means moles/liter. Physiological
concentrations are low. They are often expressed in units of millimolar (mM) = 10-3 M,
micromolar (μM) = 10-6 M, nanomolar (nM) = 10-9 M, or picomolar (pM) = 10-12 M.

F. Electrochemical Equivalence (Eq). Salts such as NaCl and CaCl2 dissociate into
positive ions (cations) and negative ions (anions). An “equivalent” is the weight in
grams of an ionic substance that replaces or combines with one gram (mole) of
monovalent H+ ions. For monovalent ions like sodium and chloride one equivalent is
equal to one GMW. For divalent ions like calcium, magnesium, and HPO42-, one
equivalent is equal to one-half a GMW. Physiological concentrations are small and are
often measured in mEq/L = 10-3 Eq/L. These units are useful when considering how
much of a substance is needed to maintain electroneutrality.

G. Complications in determining plasma concentrations. Not all ionic substances form

freely-dissociated, freely-dissolved species.

1. Many substances bind to proteins within the bloodstream or within cellular

compartments. Calcium is a prime example, being about 50% bound to albumin
and citrate in the blood.

2. Plasma volume is only 93% water. The other 7% is protein and lipid. Thus,
ionic concentrations in plasma water are somewhat underestimated when
expressed in terms whole plasma (as they are by clinical laboratories). This is
not generally a problem, but must be considered when interpreting lab data in the
presence of hyperlipidemia or hyperproteinemia.
 Body Fluid Compartments Page 5

III. DISTRIBUTION AND COMPOSITION OF BODY FLUID COMPARTMENTS

RBC PLASMA WATER

4.5% 3L BONE
3% 2L

INTERSTITIAL
CELL WATER FLUID
ECF
36% 25 L COMPARTMENT 24% 17 L
DENSE CONNECTIVE
11.5% 8L
4.5% 3L
TRANSCELLULAR WATER

1.5% 1L
Figure 2

A. Total body water makes up approximately 55 to 60% of body weight in adult males and
somewhat less, perhaps 50 to 55%, in adult females (due to a higher proportion of body
fat). Within both sexes there is considerable variability in water content, again
presumably related mainly to differences in lean body mass. For a 70 Kg man, body
water is around 42 L.

B. Body water is divided into that located inside cells and that located outside cells.

1. Intracellular fluid. Approximately 36% of body weight. This is approximately

25 L in a 70 Kg man.

2. Extracellular fluid. Approximately 24% of body weight. The two principal

extracellular fluid compartments are plasma (blood minus the red and white
cells) and the interstitial space (the space between the cells that makes up
organs). In addition, there is extracellular water located in bone and dense
connective tissue, and transcellular water in secretions such as digestive
secretions, intraocular fluid, cerebrospinal fluid, sweat, and synovial fluid.

a) A typical extracellular volume is about 17 L.

b) Plasma. A 70 Kg man has a plasma volume of about 3 L which is about
4.5% of body weight.
c) Interstitial space. The interstitial space is about 8 L in a 70 Kg man.
This is 11.5% of body weight.
d) The remaining 6 L of extracellular fluid is located in the minor
compartments.
Page 6 Body Fluid Compartments

C. Blood is composed of cells and plasma.

1. Hematocrit. Fraction of blood that is cells. Sometimes expressed as a

percentage.

2. Plasma volume = Blood volume x (1-Hct).

D. Plasma water is the initial body access point for ingested nutrients, and the exit point for
the body’s waste products. Access to all cells of the body except the red cells is via the
interstitial space.

E. The ionic composition of extracellular and intracellular compartments is markedly

different. However, the total osmotic concentrations of extracellular and intracellular
fluids are similar (despite having slightly different total ionic concentrations).

Osmotic Composition
400

Protein Protein

300 -
- HCO
HCO Other 3 Organic
3
Phosphates
Osmolarity (mOSM)

3-
- - aa's PO
4
Cl Cl -
200 HCO
++ 3
Mg ++ -
++ Mg
Ca Cl
+
K

100 + +
+ K
Na Na

+
Na
0

Plasma Interstitial Intracellular

Water Water water

Figure 3

1. The principle extracellular cation is Na+. The principle extracellular anions are
chloride and bicarbonate.

2. The principle intracellular cation is K+. The principle intracellular anions are
phosphates [both inorganic (HPO42-, H2PO4-) and organic (ATP, etc.)] and
proteins.
 Body Fluid Compartments Page 7

IV. OSMOTIC CONCEPTS, PROTEINS, AND THE DONNAN MEMBRANE EQUILIBRIUM

A. Osmotic Forces. If a semipermeable membrane separating 2 chambers obstructs the

movement of solute particles but not the solute water, water will cross the membrane
until the solute concentration on both sides of the membrane is equal. The force
generated by this water movement is often expressed in terms of osmotic pressure (π).

Initial Gl Gl Gl Gl
10 L 10 L

Final Gl Gl Gl Gl
15 L 5L
Figure 4

B. Osmotic Concentration. Particles which dissociate to form ions exert an osmotic force
in proportion to the number of osmotic particles formed. For example, 1.0 mole of NaCl,
if completely dissociated, forms a 2.0 osmolar solution. One mole of CaCl2, if
completely dissociated, forms a 3.0 osmolar solution. (Although not all ionic compounds
dissociate completely, we will assume as a first approximation that they do.) At
physiological concentrations, milliosmolar concentration units are most appropriate (1
mOSM = 10-3 osmoles/L).

C. Biological membranes are not impermeable to all solutes. Therefore, not all solutes
can exert effective osmotic forces between the various body compartments.

1. Except for plasma proteins, all ions can cross the capillary endothelial cell
membranes which separate the plasma water from the interstitium. Therefore,
only proteins (which are in higher concentration in the plasma) exert important
net osmotic forces across the capillary barrier. An increase in plasma protein
concentration causes water to move from the interstitium into the plasma. A
decrease in plasma protein concentration causes water to move from the plasma
into the interstitium.

2. Membrane pumps effectively keep Na from entering cells. The osmotic force
generated when there is an increase in extracellular sodium concentration causes
water to move out of cells into the extracellular space. The osmotic force
generated by a decrease in extracellular [Na+] causes extracellular water to move
into cells.
Page 8 Body Fluid Compartments

D. Gibbs-Donnan Membrane Equilibrium. Proteins are not only large, osmotically

active, particles, but they are also negatively charged anions. Because the proteins can
not move, the distribution of other ions is influenced in an attempt to maintain
electroneutrality (equal numbers of positive and negative charges) as well as osmotic
equilibrium on the two sides of the membrane.

50 K+ 50 K+ Total Volume
Initial 50 Cl- 50 Pr - 100 ml
100 Osmoles 100 Osmoles
67 K+
33 K+ Ions
Step 2 33 Cl-
17 Cl-
50 Pr - Move
66 Osmoles 134 Osmoles
67 K+
33 K+ H2O
Final 17 Cl-
33 Cl-
50 Pr - moves
33 ml 67 ml
Figure 5

1. Diffusible cation concentration is higher in the compartment containing non-

diffusible, anionic proteins. Diffusible anion concentration is lower in the
compartment containing the non-diffusible, anionic proteins.

2. The total osmotic forces exerted by diffusible ions is greater in the protein-
containing compartment (84) than in the protein-free compartment (66), i.e.,
there are more diffusible ionic particles in the protein-containing compartment.
This extra osmotic force from diffusible ions is added to the osmotic forces
exerted by the anionic proteins.

3. The end result of the Gibbs-Donnan effect is that more water moves into the
protein containing compartment than would be predicted on the basis of the
protein concentration alone.
 Body Fluid Compartments Page 9

V. MEASUREMENT OF BODY FLUID COMPARTMENTS

A. The measurement of body fluid compartments is based on the definition of concentration

in a well-mixed compartment:

Amount Injected
Concentration =
Volume of Distribution

B. In measuring body fluid compartments, it is necessary to correct for any substance that is
excreted during the time it takes for the injected substance to distribute itself in the
compartment of interest. Solving the corrected version of the equation for volume of
distribution yields:

(Amount Injected - Amount Excreted)

Vd =
Concentration after Equilibrium

C. To measure the volume of a compartment, one must have a substance that distributes
itself only in the volume of the compartment of interest. Volumes for compartments
where no such substance exists may be determined by subtraction.

1. Total Body Water (TBW). Deuterated water (D2O), tritiated water (THO), and
antipyrine are commonly used.

2. Extracellular Fluid Volume (ECFV). Labeled inulin, sucrose, mannitol and

sulfate are commonly used.

3. Plasma Volume (PV). Radiolabeled albumin or Evans Blue Dye (which binds
to albumin) are commonly used.

4. Intracellular Fluid Volume (ICFV). Measured by subtraction:

ICFV = TBW − ECFV 0

5. Interstitial Fluid Volume (ISFV). Measured by subtraction:

ISFV = ECFV − PV 0

VI. PRINCIPLES OF H2O MOVEMENT BETWEEN BODY COMPARTMENTS

A. Several underlying principles exemplify the distribution of body water between the body
fluid compartments.

1. Ingestion and excretion of water and electrolytes are normally regulated so as to

maintain constancy in:

a) total body water

b) total body osmolarity

2. Body water will redistribute itself so that under steady state conditions the
osmolarity of all body fluid compartments is identical and equal to total body
osmolarity.
Page 10 Body Fluid Compartments

3. Redistribution of water between the extracellular fluid compartments (the plasma

water space and interstitial fluid space) is determined by the balance of Starling
Forces acting across the capillary membrane, i.e., the balance between osmotic
and hydrostatic forces acting across the capillary endothelium. These forces will
be analyzed in detail in subsequent lectures.

4. Changes in intracellular fluid volume occur in response to changes in

extracellular fluid osmolarity, but not in response to isosmotic changes in
extracellular fluid volume.
volume. Any movement of water into or out of the
intracellular compartment will result in proportionally distributed changes in the
interstitial and plasma compartment volumes. The control of
extracellular/intracellular volume redistribution is considered in detail below.

B. Influence of extracellular fluid osmolarity on cell volume.

1. If a primary disturbance causes extracellular fluid (ECF) osmolarity to increase,

water moves out of cells and cells shrink (ICFV decreases) to maintain osmotic
equilibrium. Total body osmolarity remains higher than normal.

2. If a primary disturbance causes ECF osmolarity to decrease, water moves into the
cells and the cells swell (ICFV increases) to maintain total body osmotic
equilibrium. Total body osmolarity remains lower than normal.

C. Normal Conditions. Estimating and calculating extracellular fluid osmolarity.

1. Plasma osmolarity is representative of extracellular fluid osmolarity and is

clinically accessible. ECF osmolarity is dominated by [Na+] and the associated
anions which are necessary to maintain electroneutrality. Under normal
conditions, ECF osmolarity can be roughly estimated as:

Posm = 2 ⋅ [ Na ] p = 270 − 290 mOsm

where Posm is plasma osmolarity. Since intracellular osmolarity is the same as

extracellular osmolarity under normal conditions, this also provides an estimate
of intracellular osmolarity.
2. Clinical Laboratory Measurement. The plasma osmolarity measured in the
clinical laboratory also includes contributions from glucose and urea. Normally
the contribution from glucose and urea is small. Under certain pathological
conditions, the concentrations of these substances rise. The measured plasma
osmolarity measured by the clinical laboratory can be calculated as:

[glu cos e] p [ BUN ] p

Posm ( measured ) = 2 ⋅ [ Na ] p + +
18 2.8

where BUN signifies blood urea nitrogen, and the numbers 18 and 2.8 change
from the normal clinical concentration units (mg/dl) to milliosmolar units
(mOsm/L). Normal [glucose]p is 60-100 mg/dl, and normal [BUN]p is 10-20
mg/dl. They normally contribute about 5 mOsm each (i.e., about 2% of the
plasma osmolarity measured in the clinical lab).
 Body Fluid Compartments Page 11

3. Effective Osmolarity. Urea (BUN) crosses cell membranes just as easily as

water, so it does not contribute to redistribution of water between ECF and ICF.
Urea is therefore called and ineffective osmole. Glucose, Na+, and the anions
associated with Na+ have concentration gradients across the cell membrane and
are therefore effective osmoles in the sense that they determine the distribution of
water between ECF and ICF. Effective osmolarity is given as:

[glu cos e] p
Posm (effective) = 2 ⋅ [ Na ] p +
18

o r,
[ BUN ] p
Posm (effective) = Posm ( measured ) −
2.8

D. Osmolar Gap. If the clinically measured osmolarity is higher than that calculated using
the equation in 2 above, it suggests the presence of an unmeasured substance in the
blood. This can occur, for example, following ingestion of a foreign substance.

VII. EXAMPLE CALCULATIONS

A. Strategy for solving infusion problems. Osmolarity is the same in all compartments.

1. Calculate the initial total body solute as: (Plasma Osmolarity) x (Total Body
Water).

2. Calculate the initial extracellular solute as: (Plasma Osmolarity) x (Extracellular

Volume)

3. Calculate the new total body solute as: Previous Amt. + Amt. Added.

4. Calculate the new total body water as: Old TBW + Added Water.

5. Calculate the new total body osmolarity as: New Total Body Solute divided by
New TBW.

6. Calculate the new extracellular solute as: Old Extracellular Solute + Added
Extracellular Solute.

7. Calculate the new extracellular volume as: New Extracellular Solute divided by
New Total Body Osmolarity.

8. Calculate new intracellular volume as: New TBW - New Extracellular Volume.

9. If desired, estimate New [Na]p as: New body osmolarity divided by 2.

B. Using this strategy, calculate the effect of each of the following on intracellular volume,
extracellular volume, and plasma sodium. Initial conditions: ICF = 25 L, ECF = 17 L,
[Na]p = 140 mEq/L.

1. Ingestion of 420 mEq NaCl. Answers: ICF = 23.3 L, ECF = 18.7 L, [Na]p =
150 mEq/L.
Page 12 Body Fluid Compartments

2. Imbibing and absorbing 1.5 L of H2O. Answers: ICF = 25.9 L, ECF = 17.6 L,
[Na]p = 135 mEq/L.

3. Infusing 1.5 L of isotonic saline. Answers: ICF = 25.0 L, ECF = 18.5 L, [Na]p
= 140 mEq/L.

VIII. EFFECT OF COMMON CLINICAL CONDITIONS ON BODY H2O AND

ELECTROLYTES

A. [Na+]p is usually directly related to extracellular osmolarity and can be easily measured.

1. Hypernatremia (high blood sodium concentration) is generally indicative of

decreased intracellular fluid volume (cell shrinkage with brain cells being of
particular significance). (It’s also necessary to rule out hypoproteinemia and
hypolipidemia.)

2. Hyponatremia (low blood sodium concentration) is generally indicative of

increased intracellular fluid volume (cell swelling). (Also necessary to rule out
hyperproteinemia and hyperlipidemia).

3. In the presence of severe hyperglycemia, the glucose acts as an effective osmole

and can induce hyponatremia and cell shrinkage. The cell shrinkage, not the
hyponatremia needs correcting.

B. Conditions tending to increase extracellular osmolarity (hypernatremia), thereby

causing cell shrinkage. If water is freely accessible the hypernatremia may be prevented.
Nevertheless, hypernatremia is often seen in coma patients or infants without free access
to water.

1. Increased insensible water loss.

2. Excessive Sweat Loss. Normally, sweat is mainly water with only a little
sodium.

3. Central or nephrogenic diabetes insipidus. Decreased ADH secretion or

responsiveness to ADH.

C. Conditions tending to decrease extracellular osmolarity (hyponatremia), thereby

causing cell swelling.

1. Large water ingestion.

2. Syndrome of Inappropriate ADH Secretion (SIADH). Too much ADH leads to

water retention, hyponatremia, and excretion of concentrated urine.

D. Increased ECF volume. Increased central venous pressure (bulging of the jugular veins)
in conjunction with edema is often indicative of increased extracellular fluid volume. If
osmolarity is normal, the intracellular volume is probably normal.

E. Decreased ECF Volume. The main danger is hypovolemia which ultimately decreases
tissue perfusion. Clinical presentation includes: dry mucous membranes, lack of
urination, tenting of skin, slow capillary refill.
 Body Fluid Compartments Page 13

F. Conditions tending to cause isotonic decreases in extracellular fluid volume with little
direct effect on cell volume. Note that the fluid lost has the same osmolarity as ECF.
Volume loss stimulates thirst and ADH secretion. This results in water retention and
occasionally, secondary hyponatremia.

1. Vomiting.
2. Diarrhea.
3. Bleeding.
4. Burns. Direct loss of interstitial fluid. In addition there is protein loss, so plasma
compartment contracts.

IX. SOLUTIONS USED CLINICALLY FOR VOLUME REPLACEMENT THERAPY

A. The osmotic concentration of solutions administered clinically is generally compared to

the osmotic concentration of plasma. The osmotic concentration depends on the gram
molecular weight of the solute and its dissociablility.

1. Isotonic Solutions. Those having the same osmotic concentration as plasma.

Administration won’t alter intracellular volume.

2. Hypertonic Solutions. Those having a greater osmotic concentration than

plasma. Administration will tend to contract intracellular volume.

3. Hypotonic Solutions. Those having a lesser osmotic concentration than plasma.

Administration will tend to expand intracellular volume.

B. There are several general categories of intravenous solutions which include:

1. Dextrose Solutions. Glucose is rapidly metabolized to CO2 + H2O. The volume

therefore is distributed intracellularly as well as extracellularly.

2. Saline solutions. Come in a variety of concentrations: hypotonic (eg., 0.2%),

isotonic (0.9%), and hypertonic (eg. 5%).

3. Dextrose in Saline. Again available in various concentrations. Used for

simultaneous volume replacement and caloric supplement.

4. Plasma Expanders. For example, dextran which is a long chain polysaccharide.

These solutions are confined to the vascular compartment and preferentially
expand this portion of the ECF.