WATER BALANCE

In the normal adult organism, not undergoing changes in weight, the quantity of water supplied
daily is balanced by that eliminated, a state of equilibrium being maintained.

WATER INTAKE

Water is supplied to the body from the following source: (1) dietary liquids; (2) solid food; (3)
oxidation of organic foodstuffs.

Water comprises 70-90 per cent of the weight of the average diet of adults, even apparently
very solid foods consisting largely of water. Moreover, water is one of the chief products of combustion
of protein, fat, and carbohydrate in the body, the quantities produced by oxidation of 1 gram of each of
these substances being as follows: protein, 0.34 ml.; fat, 1.07 ml.; carbohydrate, 0.56 ml. It may be
calculated that 10-15 ml. of water are formed per 100 calories of energy produced. An ordinary 300-
calorie diet therefore contains about 450 ml. of water in the solid food and may provide an additional
300-450 ml. of water of oxidation. The remainder of the water intake is supplied by dietary liquids (Fig.
72).

WATER OUTPUT

Water leaves the body in the (1) urine, (2) feces, (3) perspiration, and (4) so-called insensible
perspiration (evaporation from skin and lungs) (Fig. 72).

Faces

Under normal conditions, the 3000-8300 ml. of digestive fluids (p. 269) entering the alimentary
tract are almost completely reabsorbed in the intestine. On an ordinary mixed diet, about 80-150ml. of
water are excreted daily in the feces of normal adults (p. 287). This may be increased considerably on a
high vegetable diet and particularly in the presence of diarrhea.

Insensible Perspiration

In the absence of active perspiration the body is continually losing water vapor from the skin
surface and lungs in inverse proportion to the relative humidity of the atmosphere. Inasmuch as 0.58
calorie is absorbed in the vaporization of 1 ml. of water, the heat lost by this process, termed insensible
perspiration, at ordinary room temperatures amounts to about 25 per cent of the total heat loss. The
latter is proportional to the quantity of water lost by insensible perspiration is therefore an obligatory
loss, determined by metabolic activity and, in a normal adult, may be calculated as 500 ml. per square
meter of body surface area per day. This amounts to about 850 ml. for a 70-kg. man (1.73 sq. meters).

Perspiration

When the environmental temperature and/or humidity rises to excessively high levels, the sweat
glands become active. Obviously, the quantity of water lost by this route varies enormously. Moreover, in
contrast 30 to 39 mEq./liter of Na and of Cl (Fig. 76, p. 341). It is a hypotonic solution, plasma containing
about 140 mEq./liter of Na. Sweating therefore removes from the body relatively more water then
electrolytes.

Urine

The urine is the important medium of elimination of water provided to the body in excess of its
fixed requirements. The kidneys have a remarkable capacity for regulating urinary excretion of water,
within wide limits, regardless of the simultaneous requirement for excretion of solids in solution (p. 843).
However, their ability to concentrate is not unlimited, a certain minimal quantity of water being required
for excretion of given among of solute. On an average adequate died (adults), providing about 50 grams
of solids for daily urinary excretion, a minimum of approximately 500 ml. of water (300 ml./sq. meter
body surface) is required for their solution. Failure to meet this obligatory urine volume requirement will
result in retention of certain urinary constituents, mainly urea, in the body fluids.

Equilibrium Requirements

As indicated above, in addition to the small amount excreted in the feces (80-150 ml.), the
minimal daily water requirement is fixed by curtain metabolic requirement: (1) loss of head by insensible
perspiration (normally about 850 ml.); (2) renal excretion of excess solid material, mainly urea and NaCl,
and therefore determined largely by the protein and salt intake (normally about 500 ml. of water ).
Consequently on an average normal diet, approximately 1500 ml. of water must be available for
elimination by these routes in the body temperature and blood urea N are to be maintained within
normal limits. The solid portion of such a diet contributes about 800 ml. of water, approximately one-
half of which is pre-formed, the remainder being produced in the course of oxidation of the organic
foodstuffs in the body. The balance of the water requirement must be supplied by intake of liquids if the
body fluids are to be maintained at a normal level.

VOLUME OF BODY FLUID COMPARTMENTS

Water comprises 60 to 70 per cent of the adult body weight, values expressed in this manner being
somewhat lower in women than in men, and decreasing with advancing age. These age and sex
differences after puberty are probably due to differences in the amount of body fat, which has a low
water content (Table 30). Classically, the body water has been regarded as existing in two main
compartments, (1) intracellular (approximately 50 per cent body), and (2) extracellular (approximately 20
per cent), the latter being further subdivided into (a) blood plasma water (about 5 per cent body weight)
and (b) interstitial fluid (about 15 per cent ). Although segregation into these anatomical compartments
is useful from many standpoints, it cannot be applied strictly to physiological considerations. This is
particularly important in relation to the distribution and exchanges of electrolytes between the various
body fluids (p. 318). From the standpoint of volume alone it seem desirable to regard the extracellular
water as existing in four main subdivisions: (1) blood plasma (about 4.5 per cent body weight); (2)
interstitial fluid and lymph (about 12 per cent); (3) dense connective tissue, cartilage and bone (about 9
per cent); (4) transcellular fluids (about 1.5 per cent). The latter term is applied to extracellular fluids
that are not simple ultrafiltrates of the blood plasma and which are formed by the transport activity of
cells (e.g., secreations of the gastrointestinal tract, liver and skin; fluids in the kidneys, eyes and
subarachnoid space).

The anatomical fluid compartments are illustrated in Figure 72. Water entering the organism,
i.e., from the gastrointestinal tract, passes into the blood stream, and equivalent amount leaving the
latter by way of the urine, lungs, skin and feces. The water of the plasma is in equilibrium with that of
the interstitical fluid and the latter with the intracellular water, across the boundaries between these
compartments, i.e,. the capillary walls and the cell membrans, respectively. The interstitial fluid, serving
as a sort of middleman for the order two fluids, acts also as a buffer which prevents rather sudden
changes in composition of the plasma, resulting from absorption from the intestine, from being reflected
directly in the intracellular fluid. More over, being a rather elastic compartments , it can expand or
contract considerably, it conditions of excessive retention (edema) or loss (dehydration) or fluid, without
comparable alterations in the volume of plasma or intracellular fluid, which must be maintained rather
rigidly in the interest of normal circulation and cell function.

The volume of (1) the circulating blood, (2) the plasma, (3) total extracellular fluid, and (4) total
body water could be measured by introduction of a substance into the body if that substance would
fulfill the following requirements: (a) be retained exclusively in the fluid compartment in question; (b)
not leave that compartment during the test period; (c0 distribute itself uniformly throughout that
compartment; (d) be capable of precise quantitative determination in the blood or plasma. A number of
methods have been proposed, none of which is entirely satisfactory; certain of them, however, have
proved useful.

Blood and Plasma Volume

(a) Carbon monoxide method. Carbon monoxide displace from hemoglobin, volume of volume,
and can be measured accurately in blood, either as CO or as HbCO. The subject breathes a
known amount of CO and the concentration oh HbCO in the blood is determined after
allowing, sufficient time for missing. If the total hemoglobin concentration is known, one can
calculate how much CO would be required to saturate the Hb to its full capacity and can
arrive at the total blood volume. By determining the hematocrit value (relative volumes of
packed cells and of plasma), the plasma volume can be derived.
(b) Radioactive iron method. Fe59 is administered to a normal or anemic subject; it becomes
incorporated in the Hb of the circulating erythrocytes. A predetermined amount of the
labeled red cells is injected intravenously in the test subject (compatible blood).
Measurement of radioactivity in blood samples withdrawn after allowing time for mixing
indicates the extent of dilution of the injected cells and permits calculation of the volumes of
blood and plasma (from hematocrit value).
(c) Dye methods. The dye employed most commonly is Evans blue (T-1824), which is adsorbed
by plasma proteins. A known amount is injected intravenously and, after allowing time for
distribution throughout the blood plasma, a sample oxalated blood is withdrawn,
centrifuged, and the concentration of dye in the plasma determined colorimetrically. The
 extend of dilution of the quantity injected can be calculated (plasma volume) and, the
hematocrit value being known, the total blood volume can be determined.
(d) I131 .labeled proteins. Serum proteins, labeled with I131, are injected intravenously and the
extent of dilution of the injected protein is determined by measurement of the radioactivity
of withdrawn blood samples.

The CO method requires cooperation of the subject, which cannot always be secured under
clinical conditions. Moreover, other technical difficulties introduce the possibility of serious
errors. Furthermore, the accuracy of this procedure, as well as of the Fe 59 method, depends
upon uniformity of distribution of all the labeled erythrocytes in the circulation. This cannot
always be assured, especially in disease states (e.g.,shock), in which variable and
undeterminable numbers of cell may be segregated in such organs as the spleen or in the
splanchnic bed. In addition, calculations of total blood volume on the basic of factors measured
in either cells or plasma are subject to inaccuracies arising out of variations in the ratio of cells to
plasma in different portions of the circulation.

One source of inaccuracy with the use of dyes and isotope-tagged serum proteins is the fact that
these proteins normally cross the capillary wall in amounts which vary in different tissues; they
are removed from the interstitial fluid mainly by the lymphatic circulation. Approximately 50 per
cent of the plasma protein pool is in the interstitial fluid-lymph compartment and, following
intravenous injection of tagged protein, the latter is evenly distributed throughout the entire
extracellular space in about 24 hours. Although under normal conditions loss of protein from the
intravascular compartment under the test conditions is not so rapid as to vitiate the usefulness
of these procedures, it may become so in many disease states in which capillary permeability is
increased.

Generally acceptable average values for blood and plasma volume in normal subjects are as
follows: whole blood, 2500-3200 ml./sq. meter body surface , or 63-80 ml./kg.; plasma, 1300-
1800 ml./sq. meter, or 35-45 ml./kg. Values for whole blood are about 7 per cent higher for men
than for women, but the plasma values are approximately the same.

Total Extracellular Fluid Volume

Application of the dilution technique to the measurement of the total volume of extracellular
fluids theoretically requires the use of a substance which, when injected intravenously, crosses
the capillary walls readily and distributes itself rapidly and uniformly throughout all extracellular
fluids, does not enter the cells, is not destroyed in the body, and is not excreated rapidly.
Substances that have been used fot this purpose include certain nonmetabolizable
carbohydrates (sucrose, mannitol, inulin) and electrolytes (thiocyanet, radioactive sodium,
radioactive chloride, sulfate, bromide). There are two major sources of inaccuracy of results
obtained with these procedures: (1)the heterogeneous character of the intracellular fluids with
respect to composition (p. 315); (2) certain of the substances employed, particularly electrolytes,
are not absolutely excluded from the intercellular compartment, but penetrate different cells to
different degrees under normal conditions and particularly in pathological states.

There are marked differences in the rates of equilibration of extracellular fluids in muscle, skin,
loose and dense connective tissue, cartilage and bone. In certain of these extracellular fluids
equilibrate rapidly; in others, e.g., dense connective tissue and cartilage and certain regions in
bones, they equilibrate very slowly. Furthermore, some of the tracer substances employed (e.g.,
inulin, mannitol) do not enter the transcellular fluids, the volumes of which may vary
enormously in certain disease states.

The major electrolytes of extracellular fluid, Na, and Cl are present in only low concentrations in
intracellular fluid generally under physiological conditions. However, both Na and Cl enter
different cells to a variable degree and not always to the same extent, the Na:Cl ratio in certain
tissues (bone, cartilage, muscle) being higher and in others (erythrocytes, connective tissue,
gastrointestinal mucosa) lower than in an ultrafiltrate of blood plasma. Moreover, there are
marked differences in the rates at which equilibrium is established between different phases of
the extracellular pool of Na. For example, in bone, which contain 35-40 per cent of the total
body Na, only about 30 per cent is rapidly exchangeable, 10 per cent slowly exchangeable
(incorporated in the bone crystal, p.650).

Values obtained by the use ogf the electrolytes tend to be too high and those with saccharides
too low. For the reasons indicated, it is preferable to use the designations, sodium space,
chloride space, thiocynate space and inulin space, etc., rather than extracellular fluid
volume . The inulin space seems to correspond most closely to the extracellular fluid volume in
most cases. Employing these procedures, values have been obtained for total extracellular fluid
volume (adults) approximating about 20 per cent of the body weight. Of this, about one-fourth is
blood plasma and three-fourth is interstitial fluid and lymph (5 amd 15 per cent, respectively, of
body weight).

Total Body Water

There is no accurate method for determining total body water, inasmuchas no measurable
substances has yet been found which, on injection, is distributed uniformly throughout the
entire body water and undergoes no metabolic change during the test period. Heavy water and
antipyrine are most satisfactory for clinical purposes.

The water content of several tissues (Table 30) has been determined by direct measurement
(animals and human biopsy or autopsy material).

COMPOSITION OF BODY FLUID COMPARTMENTS

Inasmuch as water serves chiefly as a relatively inert medium in which are conducted the
chemical reactions constituting living processes, its significance must be considered in relation to
the other components of the body fluids which , in fact, largely determine its volume and
distribution in the organism. The marked differences in composition of the intracellular and
interstitial fluids and the less striking differences between the latter and the blood plasma are
due differences in permeability of the membranes separating these compartments to the solutes
which these fluids contain.

Milliequivalents (mEq.)

Elements which combine chemically with one another do so in fixed ratios, which are functions
of their atomic weight and valences . Thus, 1.008 grams of hydrogen (at. Wt. 1.008) combines
with 8 grams of oxygen (at. Wt. 16) to form water, and with 35.457 grams of Cl (at.wt. 35.457) tp
form HCl. Similarly, 35. 457 grams of Cl combine with 22.997 grams of Na, 39.096 grams of K,
and 20.04 grams of Ca (at. Wt. 40.08). These numerical values are designed equivalent weight,
because they are equivalent in their combining power. An equivalent weight may be defined as
the weight of a molecule, or of an atom or radical (group of atoms reacting chemically as a unit ),
devided by its valence. A miliequivalent: (i.e., milligram equivalen t) is 1/1000 of the gram
equivalent weight.

The concentrations of the solid constituents of the body fluids may be expressed in terms of
weight per unit volume (e.g., miliigrams per 100 ml) or in terms of chemical combining power
(e.g.,milliquivalents per lier) (mEq./liter). The power may be converted to the latter according to
the following formula:

1
mg . ml . x 10 x valence
liter

mg .
1
mEq . =
liter

Osmolar Concentration

Although absolute osmotic equilibrium is probably never attained in living tissues, all internal
body fluids, ectracellular and intracellular, tend to have an equal osmotic pressure. Osmotic
pressure is a function of the concentration of active chemical components in a solution, i.e., the
number of ions and moles (undissociated compounds). The designation osmole in a applied to
one chemically active mole or ion. Although all solutions of identical osmolarity do not
necessarily have the same osmotic pressure (e.g., solutions of electrolytes vs. Non-electrolytes),
under conditions existing in the body fluids osmolarity may be regarded as a satisfactory
equivalent for osmotic pressure.

A solution containing 1 osmole (expressed in grams) of solute per liter of water depresses the
freezing point of the water by 1.86 0C. The freezing point of blood plasma is -0.56 0C. It must,
therefore , contain osmotically active solutes in a total concentration of 0.56/1.86 or 0.30
osmoles per liter (320 milliosmoles per liter of water). The other body fluids with equal osmotic
 pressures also have the same osmolar concentration of solutes (320 milliosmoles/liter of water),
of which non-electrolytes contribute about 10 milliosmoles.

In this connection, the components of the body fluids may be classified conveniently as follows:

1. Compounds of very large molecular size, e.g., proteins, lipids, glycogen, to which all but a
few capillary and cell membranes are almost completely impervious. Inasmuch as osmotic
pressure is proportional to the number of active chemical components per unit of water,
these compounds, because of their large molecular size, exert relatively little effect on
osmotic pressure in proportion to their concentration on a weight basis. For example, the
concentration of plasma proteins, about 7 grams per 100 ml of plasma, with molecular
weights of about 70.000 to over 1.000.000 represents only about 2 milliosmoles per liter.
Moreover, since these larger compounds displace a large volume of water and the osmolar
concentration is expressed in terms of units per liter of water, correction must be made for
this displacement. In the case of plasma, this correction factor is 0.93,the total osmolar
concentration being 301 milliosmoles per liter of plasma (320 milliosmoles per liter of
plasma water), 10 contributed by non electrolytes.
2. Electrolytes, which cross capillary walls freely, but to certain of which various cell
membranes exhibit a variable degree degree of impermeability under different conditions.
Electrolytes dissociate into ions and therefore exert an osmotic pressure greater than their
molar concentrations because the ions be have as units. The osmolar concentration of NaCl
is pratically twice its molar concentration because it dissociates almost complately into Na+
and Cl-. One millimole of CaCl 2 represents three milliosmoles, dissociating into Ca ++ + 2Cl-. In
the presence of large amounts of protein, certain elements, e.g., Ca and K, may exist as
relatively poorly dissociated salts of protein, being osmotically active only to the extendt of
the degree of dissociation.
3. Organic compounds of a molecular size which permits their free diffusion across capillary
walls, e.g., urea, glucose, amino acids. Some cell membranes many be relatively
impermeable to certain of these, as to certain electrolytes.

EXTRACELLULAR FLUID

All body cells exist in an environment of fluids collectively designated extracellular fluid. These
include the blood plasma, interstitial fluid, lymph, and peritoneal, pericardial, pleural and joint fluids.
Transcellular fluids also belong in this category (p. 312), i.e., fluids formed by the gastrointestinal mucosa
and other digestive glands, liver, kidneys, etc. These differ from other extracellular fluids in that they are
formed by active cellular mecanisms and therefore do not resemble ultrafiltrates of the blood plasma.
The heterogeneous character of the interstitial fluid is reffered to elsewhere (p. 312); from a
physiological standpoint, there are distinct differences in this respect between muscle, skin, dense
connective tissue and cartilage,and bone. With these exceptions and reservations, most of the
extracellular fluids may be regarded as having an essentially uniform qualitative composition. What
quantitative differences exist are due chiefly to differences in the concentrations of proteins, which range
from about 7 per cent in plasma and but slightly less in hepatic lymph, to about 0.1 per cent in the
subcutaneous interstitial fluid. They are solutions chiefly of NaCl and NaHCO 3 with small amounts of Ca,
Mg, K, H, phosphate, sulfate, and organis acid ions, variable amounts of protein, some non-electrolythes
(glucose, urea, lipids, etc) and with Ph values ranging from 7.35 to 7.45 under normal conditions.

The total concentration of the ionic constituents is about 310 mEq per liter of plasma (about
335 mEq per liter pf plasma water ). The difference is due mainly to the relatively high
protein content of the plasma . In accordance with the laws of electrical neutrality, cations
and anions each comprise half of the