CHAPTER 25

The Body Fluid Compartments:

Extracellular and Intracellular
Fluids, Edema

Importance:
Maintenance of relatively constant volume and stable
composition of the body is essential for homeostasis
Most common and important problems in clinical medicine
arise from abnormalities in the constancy of body fluids.
Fluid Intake and Output = Balanced during steady state
conditions
(Fluid intake = Fluid output)
Relative constancy of body fluids = due to continuous
exchange of fluid and solutes with the external environment,
as well as within different body compartments
o Fluid intake must be carefully matched by equal output
of H2O from the body to prevent body fluid volumes
from increasing or decreasing.
Daily intake of water
Sources
Ingested liquids or water in food (2100ml/day)
H2O synthesized in the body by oxidation of
carbohydrates (200ml/day)
Total H2O intake = 2300ml/day
Intake of H2O is highly variable among different people &
even within same person on different days and is dependent
on:
o Climate (inc. H2O intake during humid and hot climate)
o Habits
o Level of physical activity (inc. level of physical activity =
inc. H2O intake)

Daily loss of Body Water

Insensible water loss = unconscious loss of water from
body fluids
- Continuous loss of H2O by evaporation from the
respiratory tract and diffusion through the skin
- Accounts for 700ml/day water loss under normal conditions

Insensible water loss through skin

Occurs independently of sweating
Present even in people who are born without sweat glands
Average water loss by diffusion = 300-400ml/day
Water loss is minimized by the cholesterol-filled cornified
layer of the skin
Provides barrier against excessive loss
Cornified layer is denuded (as occurs in extensive burn
patient)
rate of evaporation increases by up to 10x (3-5L/day)
patient with burn must be given large amounts of fluid,
usually intravenously, to balance fluid loss

Insensible water loss through the Respiratory tract

- Average water loss = 300-400ml/day
- As air enters RT, it becomes saturated with moisture to vapor
pressure = 47 mmHg before it is expelled
1 | Chapter 25

Vapor pressure of inspired air < 47 mmHg, water is

continuously lost through the lungs with respiration
Cold weather = vapor pressure decreases to nearly 0
Causes greater loss of H2O from the lungs as
temperature decreases
Dry feeling in the respiratory passages in cold weather

Fluid loss in Sweat

- Amount of water lost by sweating is highly variable, depends
on physical activity and environmental temperature
o Volume of sweat =100ml/day (normal days)
o During very hot weather and during heavy
exercise = 1-2L/hour
This fluid loss would rapidly deplete body fluids
if intake will not be increased by thirst
mechanism
Water loss in feces
o 100ml/day is normally lost in the feces
o Diarrhea = increases water loss in feces to several
liters
Water loss by the kidneys
o Responsible for the remaining water loss from the
body through excretion of water in urine
o Control of excretion rate by the kidneys
Most important mechanism by which the body
maintains balance between water intake and
output as well as balance between intake and
output most electrolytes
Urine output in dehydrated person =
0.5L/day
Urine output of well hydrated person =
as high as 20L/day
o Intake of electrolytes also varies from person to
person
o Kidneys faced with the task of adjusting the
excretion rate of H2O and electrolytes to:
2 | Chapter 25

precisely match intake of substances

Compensate for excessive loss of fluid &
electrolytes that occur is certain disease states

Body fluid compartments

2 Compartments
Extracellular fluid compartment
Interstitial fluid
Blood plasma
Intracellular fluid compartment
Transcellular fluid compartment = small compartment of
fluid
o Includes fluid in:
Synovial space
Peritoneal space
Pericardial space
Intraocular spaces
Cerebrospinal fluid
o Constitutes 1-2L of the total volume of body fluid
compartments
Volume of body fluid depends on:
Age
o Body fluid volume decreases with consequent increase
in age
o Aging = increased body fat composition
Fat decreases percentage of water in the body
Premature & Newborn babies = 70-75% body weight =
body fluid volume
Gender
o Men (60%) > women (50%)
Degree of obesity/ percentage of body fat
o More obese = lesser body fluid volume

Intracellular Fluid Compartment

Fluid inside the cell
Composed of 28L of fluid in the body
Constitutes 40% of total body weight in average person
Intracellular fluid of all the different cells together is
considered to be one large fluid compartment
Extracellular Fluid Compartment
All fluids outside the cell
Constitutes 20% of the body weight (14L)
Compartment of ECF
o Interstitial fluids
Consists of (11L) of ECF
o Plasma
Consists of (3L) of ECF
Non-cellular part of blood
Exchanges substances continuously with the
interstitial fluid through pores of capillary
membranes
Pores- highly permeable to all solutes
except proteins
ECF constantly mixing, plasma and interstitial fluids have
about the same composition except for proteins, which have
higher concentration in the plasma
ECF vs. ICF
Intracellular fluid compartment
Fluid inside the cell
20% body weight (14L)
-----------

3 | Chapter 25

Blood

Volume
Contains both
ECF (fluid in
plasma)
and
ICF (fluid in
RBC)

Blood

considered as a
separate
compartment
because it is
contained in a chamber of its own which is the circulatory
system
Important in the control of CV dynamics
Average blood volume = 7% of body weight (5L)
o Plasma = 60% (3L)
o RBC = 40% (2L)
o Percentage depends on gender, weight and other
factors

Extracellular fluid compartment

Hematocrit (Packed Red Blood Cell Volume)
Fluid outside the cell
Fraction of blood composed of RBC
40% body weight (28L)
determined by centrifugation blood in a hematocrit tube until
Plasma & interstitial fluidcells become tightly packed in the bottom of the tube
True hematocrit is only about 96% of the measured
hematocrit
Measured hematocrit
o Men = 0.40
o Women = 0.36
o Person with anemia = 0.10 (barely sufficient to
sustain life)
o Polycythemia = 0.65

Polycythemia = excessive production of RBC

Constituents of Extracellular and Intracellular Fluids

Ionic composition of plasma and interstitial fluid is
similar
Most important difference = higher concentration of protein in
plasma
o Capillaries have low permeability to plasma proteins =
only small amounts of proteins are leaked into
interstitial spaces in most tissues

Donnan effect
o concentration of positively charged ions (cations) is
slightly greater (~2%) in the plasma than in the
interstitial fluid
negative charge of plasma protein tend to bind
Na and K, thus holding extra amounts of
cations in the plasma along with the plasma
proteins
o negatively charged ions (anions) have a slightly higher
concentration in the interstitial fluid compared with the
plasma
plasma protein repel negatively charged anions
o for practical purposes: concentration of ions in
interstitial fluid and plasma is considered to be
EQUAL
composition of ECF is carefully regulated by various
mechanisms, 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
separated from ECF by cell membrane that is highly
permeable to H2O but is not permeable to most electrolytes in
the body
4 | Chapter 25

contains only small quantities of Na+ and Cl- ions and almost
no Ca2+ ions
contains large amounts of K+ and phosphate ions and
moderate quantities of Mg2+ and sulfate ions

protein

cells contain large amount of

Measurement of Fluid Volumes in the Different Body Fluid

Compartments The Indicator-Dilution Principle
Indicator-dilution method
o volume of fluid compartment in the body is measured
by placing an indicator substance in the compartment,
allowing it to disperse evenly throughout the
compartments fluid then analyzing the extent to which
the substance becomes diluted
o based on the conservation of mass principle
total mass of a substance after dispersion in
fluid compartment = total mass injected into the
compartment

used to measure the volume of virtually any

compartment in the body as long as:
the indicator disperses evenly in the
compartment
indicator disperses only in the compartment
indicator is not metabolized or excreted

Antipyrine
- another substance that has been used to measure total body
water
- very lipid soluble
- can rapidly penetrate cell membranes and distribute itself
uniformly throughout the intracellular and extracellular
compartments
Measurement of Extracellular Fluid Volume

In calculating the volume

* note the total amount of substance injected into the chamber
(numerator)
* note total concentration of the fluid in the chamber after the
substance has been dispersed (denominator)

Volume of extracellular fluid

- can be estimated using any of several substances that
disperse in the plasma and interstitial fluid but do not readily
permeate the cell membrane
These substances include radioactive sodium, radioactive chloride,
radioactive iothalamate, thiosulfate ion and inulin.
- usually disperses almost completely throughout the
extracellular fluid within 30 to 60 minutes when injected into
the blood
- radioactive sodium may diffuse into the cells in small amounts
*Therefore, one frequently speaks of the sodium space or the inulin
space, instead of calling the measurement the true extracellular fluid
volume.
Calculation of Intracellular Volume
- cannot be measured directly
- however, can be calculated as:

Determination of
Compartments

Volumes

by

Specific

Body

Fluid

Intracellular volume
= Total body water Extracellular volume

Measurement of Total Body Water

Measurement of Plasma Volume

Radioactive water (tritium, 3H2O) or heavy water (deuterium, 2H2O)

- forms of water that can be used to measure total body water
- These forms of water mix with the total body water within a
few hours after being injected into the blood, and the dilution
principle can be used to calculate total body water.

Characteristics of substance used to measure plasma volume

- does not readily penetrate capillary membranes
- remains in the vascular system after injection
Some of the most commonly used substances for measuring plasma
volume

5 | Chapter 25

Serum albumin labelled with radioactive iodine (125I-albumin)

Evans blue dye (also called T-1824)

Calculation of Interstitial Fluid Volume

- cannot be measured directly , but can be calculated as:
Interstitial fluid volume
= Extracellular fluid volume Plasma volume

Measurement of Blood Volume

Blood volume
- can also be calculated if one knows the hematocrit (the
fraction of the total blood volume composed of cells) using the
following equation:

Total blood volume = Plasma volume

1-Hematocrit
e.g. if plasma volume is 3 liters and hematocrit is 0.40, total
blood volume would be calculated as
3 liters = 5 liters
1-0.4
another way to measure blood volume:
1. inject into the circulation RBCs that have been labelled
with radioactive material
2. radioactivity of a mixed blood sample can be
measured and the total blood volume can be
calculated using the indicator-dilution principle.
* radioactive chromium (51Cr), which binds tightly with
RBCs, is frequently used to label the RBCs

Regulation of Fluid Exchange and Osmotic Equilibrium between

Intracellular and Extracellular Fluid
Relative amounts of extracellular fluid distributed
between the plasma and interstitial spaces determined
mainly by the balance of hydrostatic and colloid osmotic
forces across the
6 | Chapter 25

Distribution of fluid between intracellular and

extracellular determined mainly by the osmotic effect of the
smaller solutes especially sodium, chloride and other
electrolytes that act across the cell membrane
*This is because the cell membranes are highly permeable to
water but relatively impermeable to even small ions such as
sodium and chloride. Thus, water moves across the cell
membrane rapidly and the intracellular fluid remains isotonic
with the extracellular fluid

Basic Principles of Osmosis and Osmotic Pressure

-

cell membranes are relatively impermeable to most solutes

but are highly permeable to water
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:

Solute such as sodium chloride is Solute such as sodium chloride is

added to the extracellular fluid
removed from the extracellular fluid
Water rapidly diffuses from the cells Water diffuses from the extracellular
through the cell membranes into the fluid through the cell membranes and
extracellular fluid until the water into the cells.
concentration.
- Rate of diffusion of water is called the rate of osmosis
Osmolality and Osmolarity
-

Osmolal concentration of a solution is called

osmolality when the concentration is expressed as
osmoles per kilogram of water
osmolarity when it is expressed as osmoles per litre of
solution
- easier to express body fluid quantities in litres of fluid than in
kilograms of water

* In dilute solutions such as the body fluids, these two terms can be
used almost synonymously because the differences are small.

Osmolarity of the Body Fluids

-

Calculation of the Osmolarity and Osmotic Pressure of a

Solution
-

potential osmotic pressure of a solution (cell membrane is

impermeable to solute) can be calculated using the vant
Hoffs law

e.g. Find the osmotic pressure of a 0.9 percent sodium

chloride solution.
Given: 0.9 percent solution = 0.9 gram of sodium chloride per
100 millilitres of solution,
9g/L
Molecular weight of sodium chloride = 58.5 g/mol
Thus: molarity = 9 g/L
58.5 g/mol
= 0.154 mol/L
*Because each molecule of sodium chloride is equal to 2
osmoles, the osmolarity of the solution is 0.154 x 2, or 0.308
osm/L. Osmolarity of the solution is therefore 308 mOsm/L
The potential osmotic pressure of this solution would therefore
be 308 mOsm/L x 19.3 mm Hg/mOsm/L, or 5944 mmHg.

Note: This calculation is only an approximation because sodium

and chloride ions do not behave entirely independently in solution
because of interionic attraction between them.
- deviations from the predictions of vant Hoffs law can be
corrected using a correction factor called the osmotic
coefficient
- Osmotic coefficient for sodium chloride is 0.93, thus the actual
osmolarity of 0.9 percent sodium chloride solution is 308 x
0.93, or 286 mOsm/L
*For practical reasons, the osmotic coefficients of different
solutes are sometimes neglected in determining the osmolarity
and osmotic pressures of physiologic solutions.
7 | Chapter 25

80 percent of the total osmolarity of the interstitial fluid and

plasma is due to sodium and chloride ions
almost half the osmolarity of intracellular fluid is due to
potassium ions and the remainder is divided among many
other intracellular substances
total osmolarity of each of the three compartments is about
300 mOsm/L, with the plasma being about 1 mOsm/L greater
than that of the interstitial and intracellular fluids
slight difference between plasma and interstitial fluid is
caused by the osmotic effects of the plasma proteins, which
maintain about 20 mm Hg greater pressure in the capillaries
than in the surrounding interstitial spaces

Corrected Osmolar Activity of the Body Fluids

- reason for the corrected osmolar activities of plasma,
interstitial fluid, and intracellular fluid is that cations and
anions exert interionic attraction, which can cause a slight
decrease in the osmotic activity of the dissolved substance
Osmotic Equilibrium is Maintained Between Intracellular and
Extracellular Fluids
large osmotic pressures can develop across the cell
membrane with relatively small changes in the concentration
of solutes in the extracellular fluid
for each milliosmole concentration gradient of an impermeant
solute, 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
such demonstrates the large fore 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

(without regard for whether the solute permeates the cell

membrane)

Highlyor
permeating
substances, such as urea
Cells will not shrink
cell
- can cause transient shifts in fluid volume between the
because the water
concentration in the intracellular and extracellular fluids
- but given enough time, the concentrations of these
intracellular and extracellular
substances
eventually become equal in the two
e.g. 0.9 percent solution of sodium fluids is equal and the
solutes
compartments
and have little effect on intracellular volume
chloride
cannot enter or leave the cell
under steady state conditions
5 percent glucose solution
Hypotonic
If a cell is placed in a solution that
Water will diffuse into the cell,
Osmotic
Equilibrium
Between Intracellular and Extracellular
has a lower concentration of
causing it to swell;
water
will
Fluids
is
Rapidly
Attained
impermeant solutes (<282
diffuse into the cell diluting
mOsm/L)
the intracellular fluid while
Transfer
also concentrating
theof fluid across the cell membrane
occurs
e.g. solutions of sodium chloride
extracellular fluid until
both so rapidly
the
any same
differences in osmolarities between these two
with a concentration of less than
solutions have about
compartments
are usually corrected within seconds or
0.9 percent
osmolarity
minutes
Hypertonic
If a cell is placed in a solution
Water will flow out of the
cell
having a higher concentration if
into the extracellular fluid,
movement of water across cell membrane
impermeant solutes
concentrating Rapid
the intracellular

fluid and diluting thedoes not mean that complete equilibrium occurs between the
intracellular
e.g. sodium chloride solutions of
extracellular fluid; the
cell will and extracellular compartment throughout the
greater thn 0.9 percent
shrink until the two whole body within the same short period
reason
for this is that fluid usually enters the body through the
concentrations become
equal
gut and must be transported by the blood to all tissues before
complete osmotic equilibrium can occur
Isosmotic, Hyperosmotic and Hypo-Osmotic Fluids
takes about 30 minutes to achieve osmotic equilibrium
Isotonic, hypotonic and hypertonic
everywhere in the body after drinking water
- refer to whether solutions will cause a change in cell volume
- depends on the concentration of impermeant solutes
Volume and Osmolality of Extracellular and Intracellular Fluids
Isosmotic
in Abnormal States
- solutions with an osmolarity the same as the cell
- regardless of whether the solute can penetrate the cell
Factors the can cause extracellular and intracellular volumes to
membrane
change markedly
*Some solutes, however, can permeate the cell membrane
- excess ingestion
- renal retention of water
Hyperosmotic and hypo-osmotic
- dehydration
- refer to solutions that have a higher or lower osmolarity,
- intravenous infusion of different types of solutions
respectively, compared with the normal extracellular fluid
- loss of large amounts of fluid from the gastrointestinal tract
8 | Chapter 25
Isotonic

If a cell is placed in a solution of

impermeant solutes having an
osmolarity of 282 mOsm/L

loss of abnormal amounts of fluid by sweating or through the

kidneys

Basic principles that should be kept in mind when calculating both the
changes in intracellular and extracellular fluid volumes and the types
of therapy that should be instituted:
1. Water moves rapidly across cell membranes; thus,
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); thus, the number of
osmoles in the extracellular and intracellular fluid generally
remains constant unless solutes are added to or lost from the
extracellular compartment

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
- no osmosis occurs through the cell membranes
- increase in extracellular fluid volume
- sodium and chloride largely remain in the extracellular fluid
because the cell membrane behaves as though it were
virtually impermeant to sodium chloride
If hypertonic solution is added to the extracellular fluid
- extracellular osmolarity increases and causes osmosis of
water out of the cells into the extracellular compartment
- similarly, 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
- net effect is:
- an increase in extracellular volume (greater than the volume
of fluid added)
- a decrease in intracellular volume
- a rise in osmolarity in both compartments
If hypotonic solution is added to the extracellular fluid
- osmolarity of the extracellular fluid decreases
9 | Chapter 25

some of the extracellular water diffuses into the cells until the
intracellular and extracellular compartment have the same
osmolarity
intracellular and extracellular are both increased by the
addition of hypotonic fluid
intracellular volume increases to a greater extent

Calculation of Fluid Shifts and Osmolarities After Infusion of

Hypertonic Saline Solution
(calculating the sequential effects of infusing different solutions on
extracellular and intracellular fluid volumes and osmolarities)
Sample problem: If 2 litres of hypertonic 3.0 percent sodium chloride
solution are infused into the extracellular fluid compartment of 70kilogram patient whose initial plasma osmolarity is 280 mOsm/L,
what would be the intracellular and extracellular fluid volumes and
osmolarities after osmotic equilibrium?
Step 1

Calculate the initial conditions, including the volume,

concentration and total milliosmoles in each
compartment
- extracellular fluid volume is 20 percent of body
weight
- intracellular fluid volume is 40 percent of body
weight
Calculate the total milliosmoles added to the
extracellular fluid in 2 liters of 3.0 percent sodium
chloride
- 3.0 percent solutions ~ 3.0 g/100ml or 30 grams of
sodium chloride per liter
- molecular weight of sodium chloride is 58.5 g/mol
~ 0.5128 mole of sodium per liter of solution
- 2 liters of solution ~ 1.0256 mole of sodium
chloride
- 1 mole = 2 osmoles, thus the net effect of adding 2
liters of this solution is to add 2051 milliosmoles of
sodium chloride to the extracellular fluid

Table 1. Initial Conditions

Volume (Liters)

Concentration

Extracellular fluid
Intracellular fluid
Total body fluid
Step 2

14
28
42

(mOsm/L)
280
280
280

Calculate the instantaneous effect of adding 2051

milliosmoles sodium chloride to the extracellular fluid
along with 2 liters of volume
- no change in the intracellular fluid concentration or
volume, and there would be no osmotic equilibrium
- there would be an additional 2051 milliosmoles of
total solute in the extracellular fluid, yielding a total
of 5971 milliosmoles
- calculate the concentration by dividing 5971
milliosmoles by 16 liters

Table 2. Instantaneous Effect of Adding 2 Liters of 3.0 Percent

Sodium Chloride
Volume (Liters)
Concentration
(mOsm/L)
Extracellular fluid
16
373
Intracellular fluid
28
280
Total body fluid
44
No equilibrium
Step 3

Calculate the volumes and concentrations that would

occur within a few minutes after osmotic equilibrium
develops
- concentrations in the intracellular and extracellular
fluid compartments can be calculated by (refer to
table 2) : 13,811 total mOsm/44 liters = 313.9
mOsm/L
- thus, all the body fluid compartments will have this
same concentration after osmotic equilibrium

*Assuming that no solute or water has been lost from the body and
that there is no movement of sodium chloride into or out of the cells,
the volumes of the intracellular and extracellular compartments can
be calculated.
10 | C h a p t e r 2 5

Table 3. Effect of Adding 2 Liters of 3.0 Percent Sodium Chloride After

Osmotic Equilibrium

Volume (Liters)
Extracellular fluid
Intracellular fluid
Total body fluid

19.02
24.98
44.0

Concentration
(mOsm/L)
313.9
313.0
313.9

Refer to table 3
Intracellular fluid volume: 7840/313.9 mOsm/L = 24.98 litres
Extracellular fluid volume: 5971/313.9 mOsm/L = 19.02 litres
*Note that based on this example, adding 2 liters of a hypertonic
sodium chloride solution causes more than a 5-liter increase in
extracellular fluid volume while decreasing intracellular fluid volume
by almost 3 liters.
Glucose and Other Solutions Administered For Nutritive
Purposes
Glucose solutions
- administered intravenously (to provide nutrition to people who
cannot otherwise ingest adequate amounts of nutrition)
- widely used
Amino acid and homogenized fat
- administered intravenously
- used to a lesser extent
When administered
their concentrations of osmotically active substances are
usually adjusted nearly to isotonicity
given slowly enough that they do not upset the osmotic
equilibrium of the body fluids
After the glucose and other nutrients are metabolized
excess of water often remains (especially if additional fluid
is ingested)
kidneys excrete this fluid in the form of dilute urine
net result, the addition of only nutrients to the body
5 percent glucose solution (nearly isosmotic)

5
7
1

often used to treat dehydration

can be infused intravenously without causing red blood cell
swelling (as would occur with an infusion of pure water)
reduces extracellular fluid osmolarity and therefore helps
correct the increase in extracellular fluid osmolarity associated
with dehydration

2. WATER TO THE ECF

Over-hydration
Excessive secretion of ADH

Clinical abnormalities of fluid volume regulation: hyponatremia

and hypernatremia
Plasma Sodium Concentration (PSC)

associated anions (mainly chloride) account for more than 90

percent of the solute in the extracellular fluid,
indicator of plasma osmolarity

CONSEQUENCES OF HYPONATREMIA:

HYPONATREMIA PSC below 115 to 120 mmol/L

Causes:
1.

LOSS OF SODIUM CHLORIDE FROM ECF

Dehydration
Diarrhea
Vomiting
Overuse of diuretics
Addisons disease,

11 | C h a p t e r 2 5

CELL SWELLING
brain cell edema and neurological symptoms, including headache,
nausea, lethargy, and disorientation, leading to seizures, coma,
permanent brain damage, and death
brain cannot increase its volume by more than about 10 percent
without it being for
(herniation), which can lead to permanent brain injury and death
attenuates osmotic flow of water into the cells and swelling of the
tissues
slowly developing hyponatremia, make the brain vulnerable to injury if
the hyponatremia is corrected too rapidly
if hypertonic solutions are added too rapidly to correct hyponatremia,
outpaces the brains ability to recapture the solutes lost from the cells
lead to osmotic injury of the neurons demyelination, a loss of the
myelin sheath from nerves
Correction of chronic hyponatremia:
< 10 to 12 mmol/L in 24 hours
< 18 mmol/L in 48 hours

HYPERNATREMIA PSC 158 to 160 mmol/L

Causes:

1. SODIUM CONCENTRATION

Central Diabetes insipidus (increased sodium chloride in ECF)

excessive secretion of the sodium-retaining hormone
aldosterone (increase water reabsorption)

activates defense mechanisms that protect the cell from changes in

volume.
defense mechanisms (increase the intracellular concentration of
sodium) are opposite to those that occur for hyponatremia
EDEMA

excess fluid in the body tissues

occurs mainly in the extracellular fluid compartment
can involve intracellular fluid as well

2. LOSS OF WATER FROM ECF

Inability to secrete ADH

Central Diabetes insipidus (Dehydration)
Simple dehydration
CONSEQUENCES OF HYPERNATREMIA
CELL SHRINKING

promotes intense thirst and stimulates secretion of antidiuretic

hormone, which both protect against a large increase in plasma and
extracellular fluid sodium
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
administering hypo-osmotic sodium chloride or dextrose solutions
way of correcting
prudent to correct the hypernatremia slowly in patients who have had
chronic increases in plasma sodium concentration
hyper
HYPONATREMIA (PSC below 115 to 120 mmol/L)
natre
LOSS OF SODIUM CHLORIDE FROM ECF
mia
WATER TO THE ECF
Cell swelling
(PSC 158 to 160 mmol/L)
12 | HYPERNATREMIA
Chapter 25
SODIUM CONCENTRATION
LOSS OF WATER FROM ECF
Cell shrinking

Types of Edema:
1. INTRACELLULAR EDEMA
Causes:
1. Hyponatremia
2. Depression of the metabolic systems of the tissues
3. Lack of adequate nutrition to the cells
blood flow to a tissue is decreased delivery of oxygen and
nutrients reduced blood flow too low to maintain normal
tissue metabolism cell membrane ionic pumps become
depressed sodium ions that normally leak into the interior
of the cell can no longer be pumped out of the cells excess
intracellular sodium ions osmosis of water into the cells
increase intracellular volume of a tissue area
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.
2. EXTRACELLULAR EDEMA
excess fluid accumulates in the extracellular spaces
most common clinical cause of interstitial fluid accumulation is
excessive capillary fluid filtration


Causes:
1. Abnormal leakage of fluid from the plasma to the interstitial spaces
across the capillaries,
2. Failure of the lymphatics to return fluid from the interstitium back into
the blood, often called lymphedema
CAPILLARY FILTRATION RATE

loss of the lymph vessels (radical mastectomy: interstitial

edema is usually temporary)
plasma proteins that leak into the interstitium have no other
way to be removed
rise in protein concentration raises the colloid osmotic
pressure of the interstitial fluid, which draws even more fluid
out of the capillaries.

SUMMARY OF CAUSES OF EXTRACELLULAR EDEMA

I. Increased capillary pressure
A. Excessive kidney retention of salt and water
1. Acute or chronic kidney failure

Kf : capillary filtration coefficient (the product of the

permeability and surface area of the capillaries)
Pc : capillary hydrostatic pressure
Pif : interstitial fluid hydrostatic pressure
c : capillary plasma colloid osmotic pressure
if : interstitial fluid colloid osmotic pressure
Any one of the following changes can increase the capillary filtration
rate:
1. Increased capillary filtration coefficient
2. Increased capillary hydrostatic pressure
3. Decreased plasma colloid osmotic pressure
LymphedemaFailure of the Lymph Vessels to Return Fluid and
Protein to the Blood
Lymphedema
lymphatic function is greatly impaired
blockage lymph vessels (infection by filaria nematodesWuchereria bancrofti causes elephantiasis; swelling of
scrotum- hydrocele)

2. Mineralocorticoid excess
B. High venous pressure and venous constriction
1. Heart failure
2. Venous obstruction
3. Failure of venous pumps
(a) Paralysis of muscles
(b) Immobilization of parts of the body
(c) Failure of venous valves
C. Decreased arteriolar resistance
1. Excessive body heat
2. Insufficiency of sympathetic nervous system
3. Vasodilator drugs
II. Decreased plasma proteins
A. Loss of proteins in urine (nephrotic syndrome)

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capillary filtration arterial pressure falls decreased

excretion of salt and water by the kidneys edema

B. Loss of protein from denuded skin areas

1. Burns

2. Wounds
C. Failure to produce proteins
1. Liver disease (e.g., cirrhosis)

Left-sided heart failure (without significant failure of the right side of

the heart)
blood is pumped into the lungs normally by the right side of the
heart
cannot escape easily from the pulmonary veins to the left side
of the heart
heart has been greatly weakened
all pulmonary vascular pressures pulmonary capillary pressure,
rise above normal
serious and life-threatening pulmonary edema (fluid
accumulation in the lungs can rapidly progress, causing death
within a few hours)

2. Serious protein or caloric malnutrition

III. Increased capillary permeability
A. Immune reactions that cause release of histamine and
other immune products
B. Toxins
C. Bacterial infections
D. Vitamin deficiency, especially vitamin C
E. Prolonged ischemia

Edema Caused by Decreased Kidney Excretion of Salt and

Water

F. Burns
IV. Blockage of lymph return
A. Cancer
B. Infections (e.g., filaria nematodes)
C. Surgery
D. Congenital absence or abnormality of
lymphatic vessels
Edema Caused by Heart Failure

Heart fails to pump blood from the veins into the arteries
raises venous pressure and capillary pressure increased

Reduced blood flow to the kidneys stimulates secretion of

renin increase formation of angiotensin II increased
secretion of aldosterone additional salt and water retention in
the kidneys serious generalized extracellular edema

Most sodium chloride added to the blood remains in the

extracellular compartment
Only small amounts enter the cells
In Kidney diseases:
- compromise urinary excretion of salt and water
- large amounts of sodium chloride and water added to the ECF
- salt and water leaks from the blood into the interstitial spaces
(some remains in the blood)
Main effects:
a. Increases in interstitial fluid volume (extracellular
edema)
b. Hypertension due to increase in blood volume
In children with Acute Glomerulonephritis

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renal glomeruli injured by inflammation

fails to filter adequate amounts of fluid,
serious extracellular fluid edema and severe hypertension

Edema Caused by Decreased Plasma Proteins

below 2.5 g/100 ml

failure to produce and leakage of proteins from the plasma
plasma colloid osmotic pressure falls increased capillary
filtration throughout the body extracellular edema.
Causes:
1. Nephrotic syndrome (loss of proteins in the urine)
2. Renal diseases (damage in renal glomeruli) causes
membrane to leak to the plasma proteins and often allowing
large quantities of these proteins to pass into the urine
3. Cirrhosis (development of large amounts of fibrous tissue
among the liver parenchymal cells)
4. decreased plasma colloid osmotic pressure and the
generalized edema
5. compresses the abdominal portal venous drainage vessels as
they pass through the liver before emptying back into the
general circulation
6. blocks portal venous outflow raises capillary hydrostatic
pressure throughout the gastrointestinal area increases
filtration of fluid out of the plasma into the intra-abdominal
areas ASCITES (decreased plasma protein concentration,
high portal capillary pressures, transudation of large amounts
of fluid and protein into the abdominal cavity)
SAFETY FACTORS THAT NORMALLY PREVENT EDEMA
3 Major safety factors
1. Low compliance of the interstitium when interstitial fluid
pressure is in the negative pressure range
2. Lymph flow increases 10-to 50-fold
3. Washdown of interstitial fluid protein concentration,
which reduces interstitial fluid colloid osmotic pressure as
capillary filtration increases
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Safety Factor Caused by Low

Compliance of the Interstitium in the
Negative Pressure Range
3 mm Hg - interstitial fluid
hydrostatic
pressure
most
loose
subcutaneous tissues; slightly less than
atmospheric pressure
As long as Interstitial fluid
pressure is in the negative range small
changes in interstitial fluid volume are
associated with relatively large changes
in interstitial fluid hydrostatic pressure.
NEGATIVE PRESSURE RANGE, THE COMPLIANCE IS LOW
When interstitial fluid hydrostatic pressure increases, it oppose
capillary filtration.
How does the low compliance of the tissues in the negative
pressure range act as a safety factor against edema?
negative pressure range (3 mm Hg), small increases in
interstitial fluid volume cause relatively large increases in
interstitial fluid hydrostatic pressure, opposing further filtration
of fluid into the tissues.
interstitial fluid hydrostatic pressure must increase by about
3 mm Hg before large amounts of fluid will begin to
accumulate in the tissues
safety factor against edema is a change of interstitial fluid
pressure of about 3 mm Hg.
interstitial fluid pressure rises above 0 mm Hg, the
compliance of the tissues increases, allowing large
amounts of fluid to accumulate in the tissues with relatively
small additional increases in interstitial fluid hydrostatic
pressure.
positive tissue pressure range, safety factor against edema is
lost because of the large increase in compliance of the
tissues.


Importance of Interstitial Gel in Preventing Fluid Accumulation
in the Interstitium

Prevents fluid from flowing easily through the tissues

because of impediment from the brush pile of trillions of
proteoglycan filaments
interstitial fluid pressure falls to very negative values, the gel
does not contract greatly because the meshwork of
proteoglycan filaments offers an elastic resistance to
compression.
Negative fluid pressure range, the interstitial fluid volume
does not change greatly, regardless of whether the degree
of suction is only a few millimeters of mercury negative
pressure or 10 to 20 mm Hg negative pressure
Positive pressure range, accumulation of free fluid in the
tissues ;additional increase in interstitial fluid hydrostatic
pressure. extra fluid that accumulates is free fluid because it
pushes the brush pile of proteoglycan filaments apart
Pitting edema fluid can flow freely through the tissue spaces
because it is not in gel form. can be press using the thumb
against the tissue area and push the fluid out of the area;
when the thumb is removed, a pit is left in the skin for a
few seconds until the fluid flows back from the surrounding
tissues.
Nonpitting edema tissue cells swell instead of the
interstitium
Fluid in the interstitium becomes clotted with fibrinogen so
that it cannot move freely within the tissue spaces.

Importance of the Proteoglycan Filaments as a Spacer for the

Cells and in Preventing Rapid Flow of Fluid in the Tissues

proteoglycan filaments, along with much larger collagen fibrils

in the interstitial spaces, act as a spacer between the cells
adequate spacing between the cells

16 | C h a p t e r 2 5

allows nutrients, electrolytes, and cell waste products to be

rapidly exchanged between the blood capillaries and cells
located at a distance from one another
prevent fluid from flowing too easily through the tissue
spaces
extra fluid creates large channels that allow the fluid to flow
readily through the interstitium
Therefore, when severe edema occurs in the legs, the edema
fluid often can be decreased by simply elevating the legs
diffusion of nutrients to the cells and the removal of waste
products from the cells are not compromised by the
proteoglycan filaments of the interstitium

Increased Lymph Flow as a Safety Factor Against Edema

Lymphatic system

return to the circulation the fluid and proteins filtered from the
capillaries into the interstitium
without continuous return of the filtered proteins and fluid to the
blood, the plasma volume is rapidly depleted, and interstitial
edema would occur.
lymph flow increases 10-to 50-fold when fluid begins to
accumulate in the tissues.
carry away large amounts of fluid and proteins in response to
increased capillary filtration, preventing the interstitial
pressure from rising into the positive pressure range.
safety factor by increased lymph flow 7 mm Hg
Washdown of the Interstitial Fluid Protein as a Safety
Factor Against Edema

Increase amounts of fluid are filtered into the interstitium

Increase Interstitial fluid pressure
Increased lymph flow
Decreases protein concentration of the interstitium
Larger amounts of protein are carried away than can be filtered
out of the capillaries (relatively impermeable to proteins
compared with the lymph vessels)
Proteins are washed out of the interstitial fluid as lymph

flow increases
Safety factor be about 7 mm Hg

SUMMARY OF SAFETY FACTORS THAT PREVENT EDEMA

1. Low tissue compliance in the negative pressure range
is about 3 mm Hg

resistance to the passage of fluids, electrolytes, or even

proteins, which all move back and forth between the space and
the interstitial fluid in the surrounding tissue with relative ease
potential space is in reality a large tissue space
fluid in the capillaries adjacent to the potential space diffuses not
only into the interstitial fluid but also into the potential space
Lymphatic Vessels Drain Protein from the Potential Spaces

2. Increased lymph flow is about 7 mm Hg

3. Washdown of proteins from the interstitial spaces 7 mm Hg

Total safety factor against edema: 17 mm Hg (capillary pressure in

a peripheral tissue could theoretically rise by 17 mm Hg, or
approximately double the normal value, before marked edema would
occur)
FLUIDS IN THE POTENTIAL SPACES OF THE BODY

thin layer of fluid in between, and the surfaces slide over each
other
viscous proteinaceous fluid lubricates the surfaces facilitates the
sliding,

Potential spaces

pleural cavity
pericardial cavity
peritoneal cavity
synovial cavities, including both the joint cavities and the
bursae

Fluid Is Exchanged Between the Capillaries and the Potential

Spaces

surface membrane of a potential space offer insignificant

17 | C h a p t e r 2 5

Proteins collect in the potential spaces because of leakage out of

the capillaries, similar to the collection of protein in the interstitial
spaces throughout the body.
Protein must be removed through lymphatics or other channels
and returned to the circulation
Each potential space is either directly or indirectly connected
with lymph vessels
Pleural cavity and peritoneal cavity, large lymph vessels arise
directly from the cavity itself (some cases)

Edema Fluid in the Potential Spaces Is Called Effusion

Effusion
-

edema in the subcutaneous tissues adjacent to the potential

space
- edema fluid usually collects in the potential space
- effusion fluid (Ascites) lymph blockage/multiple
- abnormalities causing excessive capillary filtration
- can cause effusion in the same way that interstitial edema is
caused; 20 liters or more of ascitic fluid can accumulate
- pleural cavity, pericardial cavity, and joint spaces, can
become seriously swollen when generalized edema is
present.
- injury or local infection in any one of the cavities often blocks
the lymph drainage, causing isolated swelling in the cavity.
Interstitial fluid hydrostatic pressure:
3 to 5 mm Hg (joint spaces)
5 to 6 mm Hg (pericardial cavity)

7 to 8 mm Hg (pleural cavity)

(A) Mannitol
(B) D2O alone
(C) Evans blue
(D) Inulin and D2O
(E) Inulin and radioactive albumin

Questions
answer: E
1. One gram of mannitol was injected into a woman. After
equilibration, a plasma sample had a mannitol
concentration of 0.08 g/L. During the equilibriation
period, 20% of the injected mannitol was excreted in the
urine. The subjects

3. Which of the following will not occur when isotonic saline

is added to the extracellular fluid compartment?

(A) extracellular fluid (ECF) volume is 1 L

(B) intracellular fluid (ICF) volume is 1 L
(C) ECF volume is 10 L
(D) interstitial volume is 12.5 L

(A) the osmolarity of the extracellular fluid does not change

(B) osmosis occurs through the cell membranes
(C) increase in extracellular fluid volume
(D) sodium and chloride largely remain in the extracellular
fluid because the cell membrane behaves as though it
were virtually impermeant to sodium chloride

answer: C

answer: B

2. Which if the following substances or combinations of

substances could be used to measure interstitial fluid
volume?

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