KOMPARTEMEN CAIRAN TUBUH DAN PENGATURANNYA

The maintenance of a relatively constant volume and a stable composition of the body fluids is essential
for homeostasis. Some of the most common and important problems in clinical medicine arise because of
abnormalities in the control systems that maintain this relative constancy of the body fluids. In this
chapter and in the following chapters on the kidneys, we discuss the overall regulation of body fluid
volume, constituents of the extracellular fluid, acid-base balance, and control of fluid exchange between
extracellular and intracellular compartments.
FLUID INTAKE AND OUTPUT ARE BALANCED DURING STEADY-STATE CONDITIONS
The relative constancy of the body fluids is remarkable because there is continuous exchange of fluid and
solutes with the external environment, as well as within the different body compartments. For example,
fluid intake is highly variable and must be carefully matched by equal output of water from the body to
prevent body fluid volumes from increasing or decreasing.
DAILY INTAKE OF WATER
Water is added to the body by two major sources: (1) it is ingested in the form of liquids or water in food,
which together normally add about 2100 ml/day to the body fluids, and (2) it is synthesized in the body
by oxidation of carbohydrates, adding about 200 ml/day. These mechanisms provide a total water intake
of about 2300 ml/day (Table 25-1). However, intake of water is highly variable among different people
and even within the same person on different days, depending on climate, habits, and level of physical
activity.
DAILY LOSS OF BODY WATER
Insensible Water Loss. Some water losses cannot be precisely regulated. For example, humans experience
a continuous loss of water by evaporation from the respiratory tract and diffusion through the skin, which
together account for about 700 ml/day of water loss under normal conditions. This loss is termed
insensible water loss because we are not consciously aware of it, even though it occurs continually in all
living humans. Insensible water loss through the skin occurs independently of sweating and is present
even in people who are born without sweat glands; the average water loss by diffusion through the skin
is about 300 to 400 ml/day. This loss is minimized by the cholesterol-filled cornified layer of the skin, which
provides a barrier against excessive loss by diffusion. When the cornified layer becomes denuded, as
occurs with extensive burns, the rate of evaporation can increase as much as 10-fold, to 3 to 5 L/day. For
this reason, persons with burns must be given large amounts of fluid, usually intravenously, to balance
fluid loss. Insensible water loss through the respiratory tract averages about 300 to 400 ml/day. As air
enters the respiratory tract, it becomes saturated with moisture, to a vapor pressure of about 47 mm Hg,
before it is expelled. Because the vapor pressure of the inspired air is usually less than 47 mm Hg, water
is continuously lost through the lungs with respiration. In cold weather, the atmospheric vapor pressure
decreases to nearly 0, causing an even greater loss of water from the lungs as the temperature decreases.
This process explains the dry feeling in the respiratory passages in cold weather.
Fluid Loss in Sweat. The amount of water lost by sweating is highly variable, depending on physical activity
and environmental temperature. The volume of sweat normally is about 100 ml/day, but in very hot
weather or during heavy exercise fluid loss in sweat occasionally increases to 1 to 2 L/hour. This fluid loss
would rapidly deplete the body fluids if intake were not also increased by activating the thirst mechanism
discussed in Chapter 29.
Water Loss in Feces. Only a small amount of water (100 ml/day) normally is lost in the feces. This loss can
increase to several liters a day in people with severe diarrhea. For this reason, severe diarrhea can be life
threatening if not corrected within a few days.
Water Loss by the Kidneys. The remaining water loss from the body occurs in the urine excreted by the
kidneys. Multiple mechanisms control the rate of urine excretion. In fact, the most important means by
which the body maintains a balance between water intake and output, as well as a balance between intake
and output of most electrolytes in the body, is by controlling the rates at which the kidneys excrete these
substances. For example, urine volume can be as low as 0.5 L/day in a dehydrated person or as high as 20
L/day in a person who has been drinking tremendous amounts of water. This variability of intake is also
true for most of the electrolytes of the body, such as sodium, chloride, and potassium. In some people,
sodium intake may be as low as 20 mEq/day, whereas in others, sodium intake may be as high as 300 to
500 mEq/day. The kidneys are faced with the task of adjusting the excretion rate of water and electrolytes
to match precisely the intake of these substances, as well as compensating for excessive losses of fluids
and electrolytes that occur in certain disease states.

BODY FLUID COMPARTMENTS

The total body fluid is distributed mainly between two compartments: the extracellular fluid and the
intracellular fluid (Figure 25-1). The extracellular fluid is divided into the interstitial fluid and the blood
plasma. There is another small compartment of fluid that is referred to as transcellular fluid. This
compartment includes fluid in the synovial, peritoneal, pericardial, and intraocular spaces, as well as the
cerebrospinal fluid; it is usually considered to be a specialized type of extracellular fluid, although in some
cases its composition may differ markedly from that of the plasma or interstitial fluid. All the transcellular
fluids together constitute about 1 to 2 liters. In a 70-kilograms adult man, the total body water is about
60 percent of the body weight, or about 42 liters.
This percentage depends on age, gender, and degree of obesity. As a person grows older, the percentage
of total body weight that is fluid gradually decreases. This decrease is due in part to the fact that aging is
usually associated with an increased percentage of the body weight being fat, which decreases the
percentage of water in the body. Because women normally have a greater percentage of body fat
compared with men, their total body water averages about 50 percent of the body weight. In premature
and newborn babies, the total body water ranges from 70 to 75 percent of body weight. Therefore, when
discussing “average” body fluid compartments, we should realize that variations exist, depending on age,
gender, and percentage of body fat. In many other countries, the average body weight (and fat mass) has
increased rapidly during the past 30 years. Currently, the average body weight for men older than 20 years
in the United States is estimated to be approximately 86.4 kg, and for women, it is 74.1 kg. Therefore the
data discussed for an “average” 70 kg man in this chapter (as well as in other chapters) would need to be
adjusted accordingly when considering body fluid compartments in most people.
INTRACELLULAR FLUID COMPARTMENT
About 28 of the 42 liters of fluid in the body are inside the 100 trillion cells and are collectively called the
intracellular fluid. Thus, the intracellular fluid constitutes about 40 percent of the total body weight in an
“average” person. The fluid of each cell contains its individual mixture of different constituents, but the
concentrations of these substances are similar from one cell to another. In fact, the composition of cell
fluids is remarkably similar even in different animals, ranging from the most primitive microorganisms to
humans. For this reason, the intracellular fluid of all the different cells together is considered to be one
large fluid compartment.
EXTRACELLULAR FLUID COMPARTMENT All the fluids outside the cells are collectively called the
extracellular fluid. Together these fluids account for about 20 percent of the body weight, or about 14
liters in a 70-kilogram man. The two largest compartments of the extracellular fluid are the interstitial
fluid, which makes up more than three fourths (11 liters) of the extracellular fluid, and the plasma, which
makes up almost one fourth of the extracellular fluid, or about 3 liters. The plasma is the noncellular part
of the blood; it exchanges substances continuously with the interstitial fluid through the pores of the
capillary membranes. These pores are highly permeable to almost all solutes in the extracellular fluid
except the proteins. Therefore, the extracellular fluids are constantly mixing, so the plasma and interstitial
fluids have about the same composition except for proteins, which have a higher concentration in the
plasma.
BLOOD VOLUME Blood contains both extracellular fluid (the fluid in plasma) and intracellular fluid (the
fluid in the red blood cells). However, blood is considered to be a separate fluid compartment because it
is contained in a chamber of its own, the circulatory system. The blood volume is especially important in
the control of cardiovascular dynamics. The average blood volume of adults is about 7 percent of body
weight, or about 5 liters. About 60 percent of the blood is plasma and 40 percent is red blood cells, but
these percentages can vary considerably in different people, depending on gender, weight, and other
factors.
Hematocrit (Packed Red Blood Cell Volume). The hematocrit is the fraction of the blood composed of red
blood cells, as determined by centrifuging blood in a “hematocrit tube” until the cells become tightly
packed in the bottom of the tube. Because the centrifuge does not completely pack the red blood cells
together, about 3 to 4 percent of the plasma remains entrapped among the cells, and the true hematocrit
is only about 96 percent of the measured hematocrit. In men, the measured hematocrit is normally about
0.40, and in women, it is about 0.36. In persons with severe anemia, the hematocrit may fall as low as
0.10, a value that is barely sufficient to sustain life. Conversely, in persons with some conditions excessive
production of red blood cells occurs, resulting in polycythemia. In these persons, the hematocrit can rise
to 0.65.

CONSTITUENTS OF EXTRACELLULAR AND INTRACELLULAR FLUIDS

Comparisons of the composition of the extracellular fluid, including the plasma and interstitial fluid, and
the intracellular fluid are shown in Figures 25-2 and 25-3 and in Table 25-2.
IONIC COMPOSITION OF PLASMA AND INTERSTITIAL FLUID IS SIMILAR Because the plasma and interstitial
fluid are separated only by highly permeable capillary membranes, their ionic composition is similar. The
most important difference between these two compartments is the higher concentration of protein in the
plasma; because the capillaries have a low permeability to the plasma proteins, only small amounts of
proteins are leaked into the interstitial spaces in most tissues. Because of the Donnan effect, the
concentration of positively charged ions (cations) is slightly greater (~2 percent) in the plasma than in the
interstitial fluid. The plasma proteins have a net negative charge and therefore tend to bind cations such
as sodium and potassium ions, thus holding extra amounts of these cations in the plasma along with the
plasma proteins. Conversely, negatively charged ions (anions) tend to have a slightly higher concentration
in the interstitial fluid compared with the plasma, because the negative charges of the plasma proteins
repel the negatively charged anions.

For practical purposes, however, the concentration of ions in the interstitial fluid and in the plasma is
considered to be about equal. Referring again to Figure 25-2, one can see that the extracellular fluid,
including the plasma and the interstitial fluid, contains large amounts of sodium and chloride ions,
reasonably large amounts of bicarbonate ions, but only small quantities of potassium, calcium,
magnesium, phosphate, and organic acid ions. The composition of extracellular fluid is carefully
regulated by various mechanisms, but especially by the kidneys, as discussed later. This regulation allows
the cells to remain continually bathed in a fluid that contains the proper concentration of electrolytes and
nutrients for optimal cell function.
INTRACELLULAR FLUID CONSTITUENTS The intracellular fluid is separated from the extracellular fluid by a
cell membrane that is highly permeable to water but is not permeable to most of the electrolytes in the
body. In contrast to the extracellular fluid, the intracellular fluid contains only small quantities of sodium
and chloride ions and almost no calcium ions. Instead, it contains large amounts of potassium and
phosphate ions plus moderate quantities of magnesium and sulfate ions, all of which have low
concentrations in the extracellular fluid. Also, cells contain large amounts of protein—almost four times
as much as in the plasma.

REGULATION OF FLUID EXCHANGE AND OSMOTIC EQUILIBRIUM BETWEEN INTRACELLULAR AND

EXTRACELLULAR FLUID
A frequent problem in treating seriously ill patients is maintaining adequate fluids in one or both of the
intracellular and extracellular compartments. As discussed in Chapter 16 and later in this chapter, the
relative amounts of extracellular fluid distributed between the plasma and interstitial spaces are
determined mainly by the balance of hydrostatic and colloid osmotic forces across the capillary
membranes. The distribution of fluid between intracellular and extracellular compartments, in contrast,
is determined mainly by the osmotic effect of the smaller solutes— especially sodium, chloride, and other
electrolytes— acting across the cell membrane. The reason for this is that the cell membranes are highly
permeable to water but relatively impermeable to even small ions such as sodium and chloride. Therefore,
water moves across the cell membrane rapidly and the intracellular fluid remains isotonic with the
extracellular fluid.
In the next section, we discuss the interrelations between intracellular and extracellular fluid volumes and
the osmotic factors that can cause shifts of fluid between these two compartments.
BASIC PRINCIPLES OF OSMOSIS AND OSMOTIC PRESSURE
The basic principles of osmosis and osmotic pressure were presented in Chapter 4. Therefore, we review
here only the most important aspects of these principles as they apply to volume regulation. Because cell
membranes are relatively impermeable to most solutes but are highly permeable to water (i.e., they are
selectively permeable), whenever there is a higher concentration of solute on one side of the cell
membrane, water diffuses across the membrane toward the region of higher solute concentration. Thus,
if a solute such as sodium chloride is added to the extracellular fluid, water rapidly diffuses from the cells
through the cell membranes into the extracellular fluid until the water concentration on both sides of the
membrane becomes equal. Conversely, if a solute such as sodium chloride is removed from the
extracellular fluid, water diffuses from the extracellular fluid through the cell membranes and into the
cells. The rate of diffusion of water is called the rate of osmosis.
Osmolality and Osmolarity. The osmolal concentration of a solution is called osmolality when the
concentration is expressed as osmoles per kilogram of water; it is called osmolarity when it is expressed
as osmoles per liter of solution. In dilute solutions such as the body fluids, these two terms can be used
almost synonymously because the differences are small. In most cases, it is easier to express body fluid
quantities in liters of fluid rather than in kilograms of water. Therefore, most of the calculations used
clinically and the calculations expressed in the next several chapters are based on osmolarities rather than
osmolalities.
OSMOTIC EQUILIBRIUM IS MAINTAINED BETWEEN INTRACELLULAR AND EXTRACELLULAR FLUIDS
Large osmotic pressures can develop across the cell membrane with relatively small changes in the
concentrations of solutes in the extracellular fluid. As discussed earlier, for each milliosmole concentration
gradient of an impermeant solute (one that will not permeate the cell membrane), about 19.3 mm Hg of
osmotic pressure is exerted across the cell membrane. If the cell membrane is exposed to pure water and
the osmolarity of intracellular fluid is 282 mOsm/L, the potential osmotic pressure that can develop across
the cell membrane is more than 5400 mm Hg. This demonstrates the large force that can move water
across the cell membrane when the intracellular and extracellular fluids are not in osmotic equilibrium.
As a result of these forces, relatively small changes in the concentration of impermeant solutes in the
extracellular fluid can cause large changes in cell volume.

Isotonic, Hypotonic, and Hypertonic Fluids. The effects of different concentrations of impermeant solutes
in the extracellular fluid on cell volume are shown in Figure 25-5. If a cell is placed in a solution of
impermeant solutes having an osmolarity of 282 mOsm/L, the cells will not shrink or swell because the
water concentration in the intracellular and extracellular fluids is equal and the solutes cannot enter or
leave the cell. Such a solution is said to be isotonic because it neither shrinks nor swells the cells. Examples
of isotonic solutions include a 0.9 percent solution of sodium chloride or a 5 percent glucose solution.
These solutions are important in clinical medicine because they can be infused into the blood without the
danger of upsetting osmotic equilibrium between the intracellular and extracellular fluids. If a cell is placed
into a hypotonic solution that has a lower concentration of impermeant solutes (<282 mOsm/L), water
will diffuse into the cell, causing it to swell; water will continue to diffuse into the cell, diluting the
intracellular fluid while also concentrating the extracellular fluid until both solutions have about the same
osmolarity. Solutions of sodium chloride with a concentration of less than 0.9 percent are hypotonic and
cause cells to swell. If a cell is placed in a hypertonic solution having a higher concentration of impermeant
solutes, water will flow out of the cell into the extracellular fluid, concentrating the intracellular fluid and
diluting the extracellular fluid. In this case, the cell will shrink until the two concentrations become equal.
Sodium chloride solutions of greater than 0.9 percent are hypertonic.
Isosmotic, Hyperosmotic, and Hypo-Osmotic Fluids. The terms isotonic, hypotonic, and hypertonic refer to
whether solutions will cause a change in cell volume. The tonicity of solutions depends on the
concentration of impermeant solutes. Some solutes, however, can permeate the cell membrane.
Solutions with an osmolarity the same as the cell are called isosmotic, regardless of whether the solute
can penetrate the cell membrane. The terms hyperosmotic and hypo-osmotic refer to solutions that have
a higher or lower osmolarity, respectively, compared with the normal extracellular fluid, without regard
for whether the solute permeates the cell membrane. Highly permeating substances, such as urea, can
cause transient shifts in fluid volume between the intracellular and extracellular fluids, but given enough
time, the concentrations of these substances eventually become equal in the two compartments and have
little effect on intracellular volume under steady-state conditions.
Osmotic Equilibrium Between Intracellular and Extracellular Fluids Is Rapidly Attained. The transfer of fluid
across the cell membrane occurs so rapidly that any differences in osmolarities between these two
compartments are usually corrected within seconds or, at the most, minutes. This rapid movement of
water across the cell membrane does not mean that complete equilibrium occurs between the
intracellular and extracellular compartments throughout the whole body within the same short period.
The reason for this is that fluid usually enters the body through the gut and must be transported by the
blood to all tissues before complete osmotic equilibrium can occur. It usually takes about 30 minutes to
achieve osmotic equilibrium everywhere in the body after drinking water.
VOLUME AND OSMOLALITY OF EXTRACELLULAR AND INTRACELLULAR FLUIDS IN ABNORMAL STATES
Some of the different factors that can cause extracellular and intracellular volumes to change markedly
are excess ingestion or renal retention of water, dehydration, intravenous infusion of different types of
solutions, loss of large amounts of fluid from the gastrointestinal tract, and loss of abnormal amounts of
fluid by sweating or through the kidneys. One can calculate both the changes in intracellular and
extracellular fluid volumes and the types of therapy that should be instituted if the following basic
principles are kept in mind: 1. Water moves rapidly across cell membranes; therefore, the osmolarities of
intracellular and extracellular fluids remain almost exactly equal to each other except for a few minutes
after a change in one of the compartments. 2. Cell membranes are almost completely impermeable to
many solutes, such as sodium and chloride; therefore, the number of osmoles in the extracellular or
intracellular fluid generally remains constant unless solutes are added to or lost from the extracellular
compartment. With these basic principles in mind, we can analyze the effects of different abnormal fluid
conditions on extracellular and intracellular fluid volumes and osmolarities.
EFFECT OF ADDING SALINE SOLUTION TO THE EXTRACELLULAR FLUID
If isotonic saline is added to the extracellular fluid compartment, the osmolarity of the extracellular fluid
does not change; therefore, no osmosis occurs through the cell membranes. The only effect is an increase
in extracellular fluid volume (Figure 25-6A). The sodium and chloride largely remain in the extracellular
fluid because the cell membrane behaves as though it were virtually impermeable to the sodium chloride.
If a hypertonic solution is added to the extracellular fluid, the extracellular osmolarity increases and causes
osmosis of water out of the cells into the extracellular compartment (see Figure 25-6B). Again, almost all
the added sodium chloride remains in the extracellular compartment and fluid diffuses from the cells into
the extracellular space to achieve osmotic equilibrium. The net effect is an increase in extracellular volume
(greater than the volume of fluid added), a decrease in intracellular volume, and a rise in osmolarity in
both compartments. If a hypotonic solution is added to the extracellular fluid, the osmolarity of the
extracellular fluid decreases and some of the extracellular water diffuses into the cells until the
intracellular and extracellular compartments have the same osmolarity (see Figure 25-6C). Both the
intracellular and the extracellular volumes are increased by the addition of hypotonic fluid, although the
intracellular volume increases to a greater extent.

CLINICAL ABNORMALITIES OF FLUID VOLUME REGULATION: HYPONATREMIA AND HYPERNATREMIA

A measurement that is readily available to the clinician for evaluating a patient’s fluid status is the plasma
sodium concentration. Plasma osmolarity is not routinely measured, but because sodium and its
associated anions (mainly chloride) account for more than 90 percent of the solute in the extracellular
fluid, plasma sodium concentration is a reasonable indicator of plasma osmolarity under many conditions.
When plasma sodium concentration is reduced more than a few milliequivalents below normal (about
142 mEq/L), a person is said to have hyponatremia. When plasma sodium concentration is elevated above
normal, a person is said to have hypernatremia.
CAUSES OF HYPONATREMIA: EXCESS WATER OR LOSS OF SODIUM
Decreased plasma sodium concentration can result from loss of sodium chloride from the extracellular
fluid or addition of excess water to the extracellular fluid (Table 25-4). A primary loss of sodium chloride
usually results in hyponatremia and dehydration and is associated with decreased extracellular fluid
volume. Conditions that can cause hyponatremia as a result of loss of sodium chloride include diarrhea
and vomiting. Overuse of diuretics that inhibit the ability of the kidneys to conserve sodium and certain
types of sodium-wasting kidney diseases can also cause modest degrees of hyponatremia. Finally,
Addison’s disease, which results from decreased secretion of the hormone aldosterone, impairs the ability
of the kidneys to reabsorb sodium and can cause a modest degree of hyponatremia. Hyponatremia can
also be associated with excess water retention, which dilutes the sodium in the extracellular fluid, a
condition that is referred to as hyponatremia— overhydration. For example, excessive secretion of
antidiuretic hormone, which causes the kidney tubules to reabsorb more water, can lead to hyponatremia
and overhydration.
CONSEQUENCES OF HYPONATREMIA: CELL SWELLING
Rapid changes in cell volume as a result of hyponatremia can have profound effects on tissue and organ
function, especially the brain. A rapid reduction in plasma sodium concentration, for example, can cause
brain cell edema and neurological symptoms, including headache, nausea, lethargy, and disorientation. If
plasma sodium concentration rapidly falls below 115 to 120 mmol/L, brain swelling may lead to seizures,
coma, permanent brain damage, and death. Because the skull is rigid, the brain cannot increase its volume
by more than about 10 percent without it being forced down the neck (herniation), which can lead to
permanent brain injury and death. When hyponatremia evolves more slowly over several days, the brain
and other tissues respond by transporting sodium, chloride, potassium, and organic solutes, such as
glutamate, from the cells into the extracellular compartment. This response attenuates osmotic flow of
water into the cells and swelling of the tissues (Figure 25-7). Transport of solutes from the cells during
slowly developing hyponatremia, however, can make the brain vulnerable to injury if the hyponatremia is
corrected too rapidly. When hypertonic solutions are added too rapidly to correct hyponatremia, this
intervention can outpace the brain’s ability to recapture the solutes lost from the cells and may lead to
osmotic injury of the neurons that is associated with demyelination, a loss of the myelin sheath from
nerves. This osmotic-mediated demyelination of neurons can be avoided by limiting the correction of
chronic hyponatremia to less than 10 to 12 mmol/L in 24 hours and to less than 18 mmol/L in 48 hours.
This slow rate of correction permits the brain to recover the lost osmoles that have occurred as a result
of adaptation to chronic hyponatremia. Hyponatremia is the most common electrolyte disorder
encountered in clinical practice and may occur in up to 15% to 25% of hospitalized patients.
CAUSES OF HYPERNATREMIA: WATER LOSS OR EXCESS SODIUM
Increased plasma sodium concentration, which also causes increased osmolarity, can be due to either loss
of water from the extracellular fluid, which concentrates the sodium ions, or excess sodium in the
extracellular fluid. Primary loss of water from the extracellular fluid results in hypernatremia and
dehydration. This condition can occur from an inability to secrete antidiuretic hormone, which is needed
for the kidneys to conserve water. As a result of lack of antidiuretic hormone, the kidneys excrete large
amounts of dilute urine (a disorder referred to as “central” diabetes insipidus), causing dehydration and
increased concentration of sodium chloride in the extracellular fluid. In certain types of renal diseases,
the kidneys cannot respond to antidiuretic hormone, causing a type of “nephrogenic” diabetes insipidus.
A more common cause of hypernatremia associated with decreased extracellular fluid volume is simple
dehydration caused by water intake that is less than water loss, as can occur with sweating during
prolonged, heavy exercise. Hypernatremia can also occur when excessive sodium chloride is added to the
extracellular fluid. This often results in hypernatremia—overhydration because excess extracellular
sodium chloride is usually associated with at least some degree of water retention by the kidneys as well.
For example, excessive secretion of the sodiumretaining hormone aldosterone can cause a mild degree
of hypernatremia and overhydration. The reason that the hypernatremia is not more severe is that the
sodium retention caused by increased aldosterone secretion also stimulates secretion of antidiuretic
hormone and causes the kidneys to also reabsorb greater amounts of water. Thus, in analyzing
abnormalities of plasma sodium concentration and deciding on proper therapy, one should first
determine whether the abnormality is caused by a primary loss or gain of sodium or a primary loss or gain
of water.
CONSEQUENCES OF HYPERNATREMIA: CELL SHRINKAGE
Hypernatremia is much less common than hyponatremia, and severe symptoms usually occur only with
rapid and large increases in the plasma sodium concentration above 158 to 160 mmol/L. One reason for
this phenomenon is that hypernatremia promotes intense thirst and stimulates secretion of antidiuretic
hormone, which both protect against a large increase in plasma and extracellular fluid sodium, as
discussed in Chapter 29. However, severe hypernatremia can occur in patients with hypothalamic lesions
that impair their sense of thirst, in infants who may not have ready access to water, in elderly patients
with altered mental status, or in persons with diabetes insipidus. Correction of hypernatremia can be
achieved by administering hypo-osmotic sodium chloride or dextrose solutions. However, it is prudent to
correct the hypernatremia slowly in patients who have had chronic increases in plasma sodium
concentration because hypernatremia also activates defense mechanisms that protect the cell from
changes in volume. These defense mechanisms are opposite to those that occur for hyponatremia and
consist of mechanisms that increase the intracellular concentration of sodium and other solutes.
EDEMA: EXCESS FLUID IN THE TISSUES
Edema refers to the presence of excess fluid in the body tissues. In most instances, edema occurs mainly
in the extracellular fluid compartment, but it can involve intracellular fluid as well. INTRACELLULAR
EDEMA Three conditions are especially prone to cause intracellular swelling: (1) hyponatremia, as
discussed earlier;
(2) depression of the metabolic systems of the tissues; and (3) lack of adequate nutrition to the cells. For
example, when blood flow to a tissue is decreased, the delivery
of oxygen and nutrients is reduced. If the blood flow becomes too low to maintain normal tissue
metabolism, the cell membrane ionic pumps become depressed. When the pumps become depressed,
sodium ions that normally leak into the interior of the cell can no longer be pumped out of the cells and
the excess intracellular sodium ions cause osmosis of water into the cells. Sometimes this process can
increase intracellular volume of a tissue area—even of an entire ischemic leg, for example—to
two to three times normal. When such an increase in intracellular volume occurs, it is usually a prelude
to death of the tissue. Intracellular edema can also occur in inflamed tissues. Inflammation usually
increases cell membrane permeability, allowing sodium and other ions to diffuse into the interior of the
cell, with subsequent osmosis of water into the cells.
EXTRACELLULAR EDEMA
Extracellular fluid edema occurs when excess fluid accumulates in the extracellular spaces. There are two
general causes of extracellular edema: (1) abnormal leakage of fluid from the plasma to the interstitial
spaces across the capillaries, and (2) failure of the lymphatics to return fluid from the interstitium back
into the blood, often called lymphedema. The most common clinical cause of interstitial fluid
accumulation is excessive capillary fluid filtration. Factors That Can Increase Capillary Filtration To
understand the causes of excessive capillary filtration, it is useful to review the determinants of capillary
filtration discussed in Chapter 16.
From this equation, one can see that any one of the following changes can increase the capillary filtration
rate: • Increased capillary filtration coefficient • Increased capillary hydrostatic pressure • Decreased
plasma colloid osmotic pressure
Lymphedema—Failure of the Lymph Vessels to Return Fluid and Protein to the Blood When lymphatic
function is greatly impaired as a result of blockage or loss of the lymph vessels, edema can become
especially severe because plasma proteins that leak into the interstitium have no other way to be
removed. The rise in protein concentration raises the colloid osmotic pressure of the interstitial fluid,
which draws even more fluid out of the capillaries. Blockage of lymph flow can be especially severe with
infections of the lymph nodes, such as occurs with infection by filaria nematodes (Wuchereria bancrofti),
which are microscopic, threadlike worms. The adult worms live in the human lymph system and are spread
from person to person by mosquitoes. People with filarial infections can have severe lymphedema and
elephantiasis and men can have swelling of the scrotum, called hydrocele. Lymphatic filariasis affects
more than 120 million people in 80 countries throughout the tropics and subtropics of Asia, Africa, the
Western Pacific, and parts of the Caribbean and South America. Lymphedema can also occur in persons
who have certain types of cancer or after surgery in which lymph vessels are removed or obstructed. For
example, large numbers of lymph vessels are removed during radical mastectomy, impairing removal of
fluid from the breast and arm areas and causing edema and swelling of the tissue spaces. A few lymph
vessels eventually regrow after this type of surgery, and thus the interstitial edema is usually temporary.