Guyton Chapter 25

Intracellular Fluid (ICF) Extracellular Fluid (ECF) Compartment

Compartment
Daily Intake of Water
Two major sources: ▪ fluid inside the cells ▪ fluids outside the cells
1. ingested in the form of liquids or water in the food = 2100 ▪ about 40 % of the total ▪ about 20 % of the body weight (14
ml/day to the body fluids body weight (28 of the liters in a normal 70-kilogram adult)
2. synthesized as a result of oxidation of carbohydrates = 42 liters of fluid in the ▪ interstitial fluid: makes up >3/4 of
about 200 ml/day body) the extracellular fluid ~ 11 L
Total water intake of about 2300 ml/day → highly variable ▪ fluid of each cell ▪ plasma: makes up about 1/4 of the
contains its individual extracellular fluid (3 liters)
mixture of different o noncellular part of the blood
Daily Loss of Body Water constituents, but the o exchanges substances
concentrations are continuously with the
Insensible Water Loss similar from one cell interstitial fluid through the
▪ Water loss that we are not consciously aware of; occurs (remarkably similar even pores of the capillary
continually in all living humans in different animals) membranes
▪ Two routes: (adds up to a total of about 700ml/day) ▪ For this reason, the ▪ Capillary pores are highly permeable
intracellular fluid of all to solutes in the ECF except the
the different cells proteins
Skin Respiratory tract (RT) together is considered to ▪ ECF are constantly mixing, so that
be one large fluid the plasma and interstitial fluids
▪ average water loss by diffusion ▪ Average water loss approx 300 compartment have about the same composition
= 300 to 400 ml/day. to 400 ml/day except for proteins, which have a
▪ occurs independently of ▪ air enters the RT → becomes higher concentration in the plasma
sweating; even in people saturated with moisture
without sweat glands (vapor pressure ≈ 47 mm Hg) Transcellular fluid Compartment
▪ loss is minimized by the ▪ vapor pressure of the inspired ▪ includes fluid in the synovial, peritoneal, pericardial, intraocular
cholesterol-filled cornified air is usually <47 mm Hg → spaces, and cerebrospinal fluid
layer of the skin water continuously lost ▪ usually considered to be a specialized type of ECF, although in some
o provides a barrier against through the lungs to humidify cases, its composition may differ from that of the plasma or
excessive loss by diffusion air interstitial fluid
o extensive burns → layer ▪ cold weather → atmospheric ▪ constitute about 1 to 2 liters
becomes denuded → rate vapor pressure decreases to
of evaporation can nearly 0 → cold air sucks even
increase as much as more moisture → greater Blood Volume
10-fold, to 3 to 5 L/day. water loss ▪ contains both extracellular fluid (the fluid in plasma) and
o burn victims must be given o explains the dry feeling intracellular fluid (the fluid in the red blood cells)
large amounts of IV fluids in the respiratory ▪ considered to be a separate fluid compartment because it is
to balance loss passages in cold weather contained in a chamber of its own: the circulatory system
▪ Ave blood volume of adults: 7 % of body weight / 5 liters
Fluid Loss in Sweat o 60 % of the blood is plasma and 40 % is RBCs (percentages
● highly variable vary depending on many factors)
● normally is about 100 ml/day Hematocrit (Packed Red Cell Volume).
● very hot weather or during heavy exercise, can increase to ▪ fraction of the blood composed of red blood cells
1 to 2 L/hour ▪ about 3 to 4 % of the plasma remains entrapped among the
● Rapidly deplete the body fluids if intake were not also cells, and the true hematocrit is only about 96 % of the
increased by activating the thirst mechanism measured hematocrit
Water Loss in Feces ▪ In men, the measured hematocrit ≈ 0.40, and in women ≈ 0.36.
● little water (100 ml/day) is normally lost in shit ▪ In severe anemia: hematocrit may fall as low as 0.10 (barely
● increase to several liters a day in people with severe sufficient to sustain life)
diarrhea → life threatening if not corrected within days ▪ Polycythemia due to excessive production of RBCs → hematocrit
can rise to 0.65
Water Loss by the Kidneys/Urine
▪ Multiple mechanisms control the rate of urine excretion Constituents of Extracellular and Intracellular Fluids
▪ Control of rates of excretion via kidneys → most important Extracellular Fluid
means by which the body maintains a balance between the ▪ Similar ionic composition due to plasma and interstitial fluid
intake and output of water and electrolytes being separated only by highly permeable capillary membranes
▪ Intake of water and most of the electrolytes (sodium, chloride, ▪ most important difference between the two compartments is
and potassium) varies a lot (by person, by intake, etc.) the higher concentration of protein in the plasma
▪ Kidney functions: o capillaries have a low permeability to the plasma proteins
o adjusting the excretion rate of water and electrolytes to → few proteins are leaked into the interstitial spaces
match intake of these substances ▪ Donnan effect
o compensating for excessive losses of fluids and electrolytes o Concentration of cations is slightly greater (about 2 %) in
the plasma than in the interstitial fluid
o The plasma proteins have a net negative charge → tend to
Body Fluid Compartments bind cations, such as sodium and potassium ions, thus
▪ In the average 70-kilogram adult human, the total body water is holding extra amounts of these cations in the plasma along
about 60 % of the body weight (about 42 liters) with the plasma proteins
o Varies depending on age, gender, and degree of obesity. o Concentrations of negatively charged ions (anions) →
▪ ↑ % of body fat → ↓ % of water in body slightly higher in the interstitial fluid because the negative
o Person grows older → ↓% of total fluid body weight charges of the plasma proteins repel the negatively charged
o due to the fact that aging is usually associated anions
with an ↑% of body fat o For practical purposes, however, the concentration of ions
o women normally have more body fat than men → contain in the interstitial fluid and in the plasma is considered to be
slightly less water than men about equal.
▪ The composition of ECF is carefully regulated by various
mechanisms, but especially by the kidneys → 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
▪ separated from the ECF by a cell membrane that is highly
permeable to water but not to most of the electrolytes in the
body
▪ In contrast to the ECF, the ICF contains only small quantities of
sodium and chloride ions and almost no calcium ions
▪ contains large amounts of potassium and phosphate ions plus
moderate quantities of magnesium and sulfate ions
▪ cells contain large amounts of protein, almost four times as
much as in the plasma.
Measurement of Fluid Volumes in the Different Body Fluid
Compartments-The Indicator-Dilution Principle
They measure the volume of a fluid compartment
in the body by placing an indicator substance in
the compartment, allowing it to disperse evenly
throughout the compartment's fluid, and then
analyzing the extent to which the substance
becomes diluted
Determination of Volumes of Specific Body Fluid Compartments
Regulation of Fluid Exchange and Osmotic Equilibrium Between
Intracellular and Extracellular Fluid
▪ maintaining adequate fluids in one or both of the intracellular
and extracellular compartments is frequent problem in treating
seriously ill patients
▪ relative amounts of ECF distributed between the plasma and
interstitial spaces are determined mainly by the balance of
hydrostatic and colloid osmotic forces across the capillary
membranes
▪ distribution of fluid between ICF and ECF compartments
determined mainly by the osmotic effect of the smaller solutes
(especially sodium, chloride, and other electrolytes-acting across
the cell membrane)
o the reason: cell membranes are highly permeable to water
but relatively impermeable to small ions such as sodium
and chloride → water moves across the cell membrane
rapidly → that the ICF remains isotonic with the ECF
Basic Principles of Osmosis and Osmotic Pressure
▪ Osmosis: the net diffusion of water across a selectively
permeable membrane from a region of high water
concentration to one that has a lower water concentration
▪ cell membranes are relatively impermeable to most solutes but
highly permeable to water (i.e., selectively permeable),
o if a solute is added to the extracellular fluid, water rapidly
diffuses into the extracellular fluid
o if a solute is removed from the extracellular fluid, water
diffuses from the extracellular fluid into the cells
▪ Rate of osmosis: rate of water diffusion
Relation Between Moles and Osmoles
▪ Osmoles: the total number of particles in a solution
▪ osmole refers to the number of osmotically active particles in a
solution
▪ 1 osmole (osm) = 1 mole (mol) x (6.02 × 1023) of solute particles
▪ milliosmole (mOsm) = 1/1000 osmole (more commonly used
since the osmole is too large of a unit)
Osmolality and Osmolarity
▪ Osmolality: The osmolal concentration of a solution when
expressed as osmoles per kg of water
▪ Osmolarity expressed as osmoles per liter of solution; more
commonly used than osmolality
▪ In dilute solutions such as the body fluids, these two terms can
be used almost synonymously because the differences are small
Osmotic Pressure
▪ Osmosis of water membrane can be opposed by applying a
pressure in the opposite direction
▪ Osmotic pressure: precise amount of pressure required to
prevent the osmosis
o indirect measurement of the water and solute
concentrations of a solution
o 🡩 osmotic pressure 🡪 🡫 the water concentration and 🡩
solute concentration
Relation Between Osmotic Pressure and Osmolarity
▪ The osmotic pressure of a solution is directly proportional to the
concentration of osmotically active particles in that solution.
▪ the osmotic pressure of a solution is proportional to its
osmolarity, a measure of the concentration of solute particles.
▪ Expressed mathematically, according to van't Hoff's law, osmotic
pressure (π) can be calculated as
π = CRT
▪ where C is the concentration of solutes in osmoles per liter, R is
the ideal gas constant, and T is the absolute temperature in
degrees kelvin (273° + C°). π is expressed in mm Hg
Calculation of the Osmolarity and Osmotic Pressure of a Solution
▪ Using van't Hoff's law, one can calculate the potential osmotic
pressure of a solution, assuming that the cell membrane is
impermeable to the solute
Regardless of whether the solute can penetrate the cell membrane, a
solution is:
▪ Isosmotic: solutions with an osmolarity the same as the cell
▪ Hyperosmotic: solution that have higher osmolarity than normal
ECF
Hypo-osmotic: solutions that have lower osmolarity than normal ECF

▪
Osmolarity of the Body Fluids
▪ about 80 % of the total osmolarity of the interstitial fluid and
plasma of the ECF is due to sodium and chloride ions
▪ about half the osmolarity of the ICF is due to potassium ions
(remainder is other intracellular shit)
▪ 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 due to
osmotic effects of the plasma proteins, which maintain about Osmotic Equilibrium Between Intracellular and Extracellular Fluids
20 mm Hg greater pressure in the capillaries than in the Is Rapidly Attained
surrounding interstitial spaces ▪ The transfer of fluid across the cell membrane occurs so rapidly
that any differences in osmolarities between these two
Corrected Osmolar Activity of the Body Fluids compartments are usually corrected within seconds or, at the
▪ molecules and ions in solution exert interionic and most, minutes.
intermolecular attraction or repulsion from one solute molecule ▪ fluid usually enters the body through the gut and must be
to the next transported by the blood to all tissues before complete osmotic
o Attraction: cause slight decrease in osmotic activity of the equilibrium can occur
dissolved substance ▪ usually takes about 30 minutes to achieve osmotic equilibrium
o Repulsion: cause slight increase in osmotic activity of the everywhere in the body after drinking water.
dissolved substance
Volume and Osmolality of Extracellular and Intracellular Fluids in
Total Osmotic Pressure Exerted by the Body Fluids Abnormal States
▪ total pressure that would be exerted if it were placed on one
side of the cell membrane with pure water on the other side Factors that can cause extracellular and intracellular volumes to
▪ averages about 5443 mm Hg for plasma, which is 19.3 times the change
corrected osmolarity of 282 mOsm/L ▪ ingestion of water
▪ dehydration
Osmotic Equilibrium Is Maintained Between Intracellular and ▪ intravenous infusion of different types of solutions
Extracellular Fluids ▪ loss of large amounts of fluid from the gastrointestinal tract
▪ Large osmotic pressures can develop across the cell membrane ▪ loss of abnormal amounts of fluid by sweating or through the
with relatively small changes in the concentrations of solutes in kidneys
the extracellular fluid.
▪ for each milliosmole concentration gradient of an impermeant One can calculate both the changes in intracellular and extracellular
solute (will not permeate the cell membrane), about 19.3 mm fluid volumes and the types of therapy that should be instituted if the
Hg osmotic pressure is exerted across the cell membrane. following basic principles are kept in mind:
▪ large forces exists that can move water across the cell 1. Water moves rapidly across cell membranes; therefore, the
membrane when the intracellular and extracellular fluids are not osmolarities of intracellular and extracellular fluids remain
in osmotic equilibrium → relatively small changes in the almost exactly equal to each other except for a few minutes
concentration of impermeant solutes in the ECF can cause large after a change in one of the compartments.
changes in cell volume. 2. Cell membranes are almost completely impermeable to
many solutes; therefore, the number of osmoles in the
Isotonic, Hypotonic, and Hypertonic Fluids extracellular or intracellular fluid generally remains
constant unless solutes are added to or lost from the
Isotonic Hypotonic Hypertonic extracellular compartment.
Possible to analyze the effects of different abnormal fluid conditions
If a cell is placed in a sol if a cell is placed into a cell is placed in a on extracellular and intracellular fluid volumes and osmolarities.
impermeant solutes with an a solution that has solution having a
osmolality of 282 mOsm/L a lower higher
→ cell will not shrink or concentration of concentration of
swell impermeant impermeant
solutes (<282 solutes, water will
water concentration in the mOsm/L), water flow out of the cell
intracellular and will diffuse into the into the ECF → cell
extracellular fluids is equal cell → cell will will shrink
and the solutes cannot enter swell
or leave the cell NaCl solutions of
Solutions of NaCl greater than 0.9 per
0.9 % solution of NaCl or a 5 with a cent are hypertonic.
% glucose solution concentration <0.9
(can be infused into the %
blood without the danger of
upsetting osmotic
equilibrium)
Effect of Adding Saline Solution to the Extracellular Fluid Abnormalities of Body Fluid Volume Regulation: Hyponatremia and
Hypernatremia
Isotonic saline Hypertonic Hypotonic solution Abnormality Cause Plasma ECF ICF
solution solution Na+ Vol V
Conc
the osmolarity of the The extracellular the osmolarity of the
extracellular fluid osmolarity increases extracellular fluid Hypo-osmotic Adrenal ↓ ↓ ↑
does not change → and causes osmosis of decreases and some dehydration insufficiency
no osmosis water out of the cells of the extracellular
Overuse of diuretics
into the extracellular water diffuses into
Only effect = increase compartment. the cells until the
ECF volume. The intracellular and Hypo-osmotic Excess ADH ↓ ↑ ↑
sodium and chloride Again, almost all the extracellular overhydration Bronchogenic tumor
largely remain in the added NaCl remains in compartments have
extracellular fluid the extracellular the same osmolarity. Hyper-osmotic Diabetes insipidus ↑ ↓ ↓
because the cell compartment, and dehydration Excessive sweating
membrane behaves as fluid diffuses from the Both the intracellular
though it were cells into the and the extracellular
virtually impermeable extracellular space to volumes are
Hyper-osmotic Cushing's disease ↑ ↑ ↓
to the NaCl. achieve osmotic increased, although overhydration Primary
equilibrium. the intracellular aldosteronism
Net effect is an volume increases to a
increase in greater extent.
extracellular volume Causes of Hyponatremia: Excess Water or Loss of Sodium
(greater than the ▪ Usually associated with decreased ECF volume
volume of fluid ▪ Diarrhea and vomiting → loss of NaCl
added), a decrease in ▪ Overuse of diuretics inhibit the kidneys’ ability to conserve
intracellular volume, sodium
and a rise in ▪ Addison's disease: decreased secretion of aldosterone
osmolarity in both
o impairs the ability of the kidneys to reabsorb sodium and
compartments.
can cause a modest degree of hyponatremia
▪ Hypo-osmotic overhydration: excess water retention → dilutes
Calculation of Fluid Shifts and Osmolarities After Infusion of the sodium in the ECF
Hypertonic Saline. o excessive secretion of antidiuretic hormone → kidney
*I omitted this section because it was all calculations, if you think it’s tubules reabsorb more water → lead to hyponatremia and
important refer to pages 299 and 300* overhydration
Consequences of Hyponatremia
● Profound effects on organs, especially on the brain
Glucose and Other Solutions Administered for Nutritive Purposes ● Rapid reduction in plasma sodium → cause brain cell
▪ Glucose solutions are widely used, and amino acid and edema and neurological symptoms
homogenized fat solutions are used to a lesser extent ● Plasma sodium falls below 115 to 120 mmol/L → brain
▪ When administered, their concentrations of osmotically active swelling leading to seizures, coma, permanent brain
substances are usually adjusted nearly to isotonicity, or they are damage and death and brain herniation down the neck
given slowly enough that they do not upset the osmotic ● Hyponatremia evolve more slowly over several days →
equilibrium of the body fluids. brain and other tissues respond by transporting Na, Cl, K,
▪ After the glucose or other nutrients are metabolized, an excess and organic solutes from the cells into the EC compartment
of water often remains → kidneys excrete this in the form of a ● Brain injury can occur if hyponatremia is corrected too
very dilute urine → net result: addition of only nutrients to the rapidly
body ○ intervention can outpace the brain’s ability to
▪ 5% glucoses solution used to treat dehydration recapture solutes lost from the cells and lead to
o solution is isosmotic → can be infused intravenously w/o osmotic injury of the neurons → associated with
causing red blood cell swelling demyelination
o glucose is rapidly transported into the cells and ○ avoided by limiting the correction to less than
metabolized → infusion of a 5% glucose sol reduces the 10-12 mmol/L in 24 hrs and to less than 18
ECF osmolarity and helps correct increase in ECF osmolarity mmol/L in 48 hrs
associated with dehydration ● Hyponatremia → most common electrolyte disorder

Clinical Abnormalities of Fluid Volume Regulation: Hyponatremia
and Hypernatremia
▪ plasma sodium concentration: primary measurement for
evaluating a patient's fluid status is the.
o Hyponatremia When plasma sodium concentration is
reduced below normal (about 142 mEq/L)
o Hypernatremia When plasma sodium concentration is
elevated above normal
Causes of Hypernatremia: Water Loss or Excess Sodium
▪ antidiuretic hormone: needed for the kidneys to conserve water
▪ hyperosmotic dehydration: can occur from an inability to
secrete this hormone
▪ diabetes insipidus: lack of ADH → increase kidney excretion of
dilute urine → dehydration and increase concentration of NaCl
in the ECF
o nephrogenic diabetes insipidus: type of renal disease;
kidneys cannot respond to antidiuretic hormone
▪ more common cause → dehydration caused by inadequate
water intake
▪ excessive secretion of aldosterone (sodium-retaining hormone)
→ cause mild degree of hypernatremia and overhydration
o The reason that the hypernatremia is not more severe is
that increased aldosterone secretion causes the kidneys to
reabsorb greater amounts of water as well as sodium.
Consequences of Hypernatremia: Cell shrinkage o lymph vessels eventually regrow after this type of
● much less common than hyponatremia surgery
● severe symptoms usually occur only with rapid and large
increase in the plasma sodium concentration above Summary of Causes of Extracellular Edema
158-160mmol/L
● hypernatremia promotes intense thirst and stimulates I. Increased capillary pressure
secretion of antidiuretic hormone → protect against a large A. Excessive kidney retention of salt and water
increase in plasma and ECF sodium 1. Acute or chronic kidney failure
● severe hypernatremia can occur in patients with 2. Mineralocorticoid excess
hypothalamic lesions → impair sense of thirst (ex. diabetes B. High venous pressure and venous constriction
insipidus, altered mental status, infants who may not have 1. Heart failure
ready access to water) 2. Venous obstruction
● Correction of hypernatremia achieved by administering 3. Failure of venous pumps
hypo-osmotic sodium chloride or dextrose solutions a. Paralysis of muscles
● prudent to correct the hypernatremia slowly in patients b. Immobilization of parts of the
who have had chronic increases due to defense body
mechanisms that protect the cell from changes in volume c. Failure of venous valves
○ opposite to those that occur for hyponatremia C. Decreased arteriolar resistance
1. Excessive body heat
EDEMA 2. Insufficiency of sympathetic nervous
system
Intracellular Edema 3. Vasodilator drugs
▪ Two conditions prone to cause intracellular swelling: II. Decreased plasma proteins
1. hyponatremia A. Loss of proteins in urine (nephrotic syndrome)
2. depression of the metabolic systems of the tissues B. Loss of protein from denuded skin areas
3. lack of adequate nutrition to the cells 1. Burns
▪ ↓blood flow to a tissue → ↓ delivery of oxygen and nutrients. 2. Wounds
▪ ↓blood flow → the cell membrane ionic pumps become C. Failure to produce proteins
depressed → sodium ions that normally leak into the interior of 1. Liver disease (e.g., cirrhosis)
the cell can no longer be pumped out of the cells, and the excess 2. Serious protein or caloric malnutrition
sodium ions inside the cells cause osmosis of water into the cells III. Increased capillary permeability
→ can increase intracellular volume of a tissue area → can lead A. Immune reactions that cause release of histamine
to death of tissue and other immune products
▪ also occur in inflamed tissues. B. Toxins
o Inflammation usually has a direct effect on the cell C. Bacterial infections
membranes to increase their permeability, allowing sodium D. Vitamin deficiency, especially vitamin C
and other ions to diffuse into the interior of the cell, with E. Prolonged ischemia
subsequent osmosis of water into the cells. F. Burns
IV. Blockage of lymph return
Extracellular Edema A. Cancer
▪ Extracellular fluid edema occurs when there is excess fluid B. Infections (e.g., filaria nematodes)
accumulation in the extracellular spaces C. Surgery
▪ two general causes of extracellular edema: D. Congenital absence or abnormality of lymphatic
1. abnormal leakage of fluid from the plasma to the vessels
interstitial spaces across the capillaries
2. failure of the lymphatics to return fluid from the Edema Caused by Heart Failure
interstitium back into the blood ▪ One of the most serious and most common causes of edema
● excessive capillary fluid filtration: most common ▪ heart fails to pump blood normally from the veins into the
cause of interstitial fluid accumulation arteries → increase venous pressure and capillary pressure →
increased capillary filtration.
Factors That Can Increase Capillary Filtration ▪ decreased arterial pressure → decreased excretion of salt and
▪ Filtration = Kf x (Pc - Pif - πc + πif ) water by the kidneys → increased blood volume and further
o Kf is the capillary filtration coefficient (the product of the raises capillary hydrostatic pressure to cause still more edema.
permeability and surface area of the capillaries), ▪ decreased blood flow to the kidneys due to heart failure →
o Pc is the capillary hydrostatic pressure stimulates secretion of renin → increase formation of
o Pif is the interstitial fluid hydrostatic pressure angiotensin II and → secretion of aldosterone → increase salt
o πc is the capillary plasma colloid osmotic pressure and water retention by the kidneys
o πif is the interstitial fluid colloid osmotic pressure ▪ left-sided heart failure but without right-sided failure → blood is
▪ From this equation, the following changes can increase the pumped into the lungs normally by the right side of the heart
capillary filtration rate (moving from the plasma to interstitial but cannot escape easily from the pulmonary veins to the left
fluid): side of the heart → increased pulmonary vascular pressures,
o Increased capillary filtration coefficient including pulmonary capillary pressure → serious and
o Increased capillary hydrostatic pressure life-threatening pulmonary edema.
o Decreased plasma colloid osmotic pressure o When untreated, fluid accumulation in the lungs can
rapidly progress → death
Lymphatic Blockage Causes Edema
▪ blockage lymph vessels → plasma proteins that leak into the Edema Caused by Decreased Kidney Excretion of Salt and Water
interstitium have no other way to be removed → increase ▪ in kidney diseases that compromise urinary excretion of salt and
protein concentration → increase the colloid osmotic pressure water, large amounts of sodium chloride and water are added to
of the interstitial fluid → draws even more fluid out of the the extracellular fluid
capillaries. ▪ Most of this salt and water leaks from the blood into the
▪ can be especially severe with infections of the lymph nodes (ie. interstitial spaces, but some remains in the blood.
filaria nematodes) W. bancrofti ▪ The main effects:
▪ can occur in certain types of cancer or after surgery in which 1. widespread increases in interstitial fluid volume
lymph vessels are removed or obstructed (ex. radical (extracellular edema)
mastectomy) 2. hypertension because of the increase in blood volume
 ▪ Acute glomerulonephritis (in children): renal glomeruli injured
by inflammation → fail to filter adequate amounts of fluid →
develop serious extracellular fluid edema
o along with the edema → develop severe hypertension
Edema Caused by Decreased Plasma Proteins
▪ failure to produce normal amounts of proteins or leakage of
proteins from the plasma → decreased plasma protein
concentration → decreased plasma colloid osmotic pressure →
increased capillary filtration throughout the body →
extracellular edema
▪ Nephrotic syndrome: loss of proteins in the urine in certain
kidney diseases → decreased plasma protein concentration
▪ diseases can damage the membranes of the renal glomeruli →
membranes become leaky to the plasma proteins → proteins
pass into the urine
o Serious generalized edema occurs when the plasma
protein concentration falls below 2.5 g/100 ml
▪ Cirrhosis of the liver: development of large amounts of fibrous
tissue among the liver parenchymal cells → causes a reduction
in plasma protein concentration
o result is failure of the liver cells to produce sufficient
plasma proteins, leading to decreased plasma colloid
osmotic pressure and the generalized edema
o another way that liver cirrhosis causes edema: liver fibrosis
compresses the abdominal portal venous drainage vessels
as they pass through the liver before emptying back into
the general circulation → increase capillary hydrostatic
pressure throughout the gastrointestinal area → increase
filtration of fluid out of the plasma into the intra-abdominal
areas
▪ combined effects of decreased plasma protein
concentration and high portal capillary pressures
cause transudation of large amounts of fluid and
protein into the abdominal cavity, a condition referred
to as ascites
Safety Factors That Normally Prevent Edema
▪ Three major safety factors prevent excessive fluid accumulation
in the interstitial spaces:
1. Low compliance of the interstitium when interstitial fluid
pressure is in the negative pressure range
2. the ability of lymph flow to increase 10- to 50-fold
3. washdown of interstitial fluid protein concentration,
which reduces interstitial fluid colloid osmotic pressure
as capillary filtration increases
Safety Factor Caused by Low Compliance of the Interstitium in the
Negative Pressure Range
▪ ↑ interstitial fluid hydrostatic pressure → ↓ capillary filtration
▪ interstitial fluid hydrostatic pressure in the negative pressure
range: small increases in interstitial fluid volume → relatively
large increases in interstitial fluid hydrostatic pressure, opposing
further filtration of fluid into the tissues
▪ Safety factor: normal interstitial fluid hydrostatic pressure is -3
mm Hg
o interstitial fluid hydrostatic pressure must increase by
about 3 mm Hg before large amounts of fluid begin to
accumulate in the tissue
▪ when interstitial fluid pressure > 0 mm Hg → increase
compliance → large amounts of fluid accumulate in the tissues
with relatively small additional increases in interstitial fluid
hydrostatic pressure.
o Thus, in the positive tissue pressure range, this safety factor
is lost because of the large increase in compliance of the
tissues
Importance of Interstitial Gel in Preventing Fluid Accumulation in the
Interstitium
▪ in normal tissues with negative interstitial fluid pressure, the
fluid in the interstitium is in gel form.
o fluid is bound in a proteoglycan meshwork so that there
are virtually no "free" fluid spaces larger than a few
hundredths of a micrometer in diameter.
▪ gel prevents fluid from flowing easily through the tissues
because of impediment from the "brush pile" of trillions of
proteoglycan filaments
▪ Also, when the 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
▪ In the negative fluid pressure range, the interstitial fluid volume
does not change greatly (compliance of the tissues is very low)
▪ Free fluid: the extra fluid that accumulates because it pushes
the brush pile of proteoglycan filaments apart
o fluid can flow freely through the tissue spaces because it is
not in gel form
o accumulates when interstitial fluid pressure rises to the
positive pressure range
o Pitting edema: one can press 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
o Nonpitting edema: when the tissue cells swell instead of
the interstitium or when the 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
o allows nutrients, electrolytes, and cell waste products to
be rapidly exchanged between the blood capillaries and
cells located at a distance from one another
▪ proteoglycan filaments also prevent fluid from flowing too easily
through the tissue spaces
▪ without proteoglycan filaments, standing up would cause large
amounts of interstitial fluid to flow from the upper body to the
lower body
▪ when too much fluid accumulates in the interstitium, extra fluid
creates large channels that allow the fluid to flow readily
through the interstitium
o when severe edema occurs in the legs, the edema fluid can
be decreased by elevating the legs
Increased Lymph Flow as a Safety Factor Against Edema
▪ A major function of the lymphatic system is to return to the
circulation the fluid and proteins filtered from the capillaries
into the interstitium.
o Without this the plasma volume would be rapidly depleted,
and interstitial edema would occur
▪ lymph flow can increase 10- to 50-fold when fluid begins to
accumulate in the tissues
o allows the lymphatics to 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
o safety factor calculated to be about 7 mm Hg
"Washdown" of the Interstitial Fluid Protein as a Safety Factor
Against Edema
▪ As increased amounts of fluid are filtered into the interstitium
→ increased interstitial fluid pressure → increased lymph flow
▪ In most tissues, the protein concentration of the interstitium
decreases as lymph flow is increased, because larger amounts
of protein are carried away than can be filtered out of the
capillaries
o reason for this is the capillaries are relatively impermeable
to proteins, compared with the lymph vessels
o proteins are "washed out" of the interstitial fluid as lymph
flow increases
▪ the interstitial fluid colloid osmotic pressure tends to draw
fluid out of the capillaries
 o decreased interstitial fluid proteins → decreased net
filtration force across the capillaries → prevent further
accumulation of fluid
▪ The safety factor has been calculated to be about 7 mm Hg

Summary of Safety Factors That Prevent Edema

Putting together all the safety factors against edema, we find the
following:
1. The safety factor caused by low tissue compliance in the
negative pressure range is about 3 mm Hg.
2. The safety factor caused by increased lymph flow is about 7
mm Hg
3. The safety factor caused by washdown of proteins from the
interstitial spaces is about 7 mm Hg.
Therefore, the total safety factor against edema is about 17 mm Hg.
This means that the 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

▪ Potential space: have surfaces that almost touch each other,
with only a thin layer of fluid in between
o pleural cavity, pericardial cavity, peritoneal cavity, synovial
cavities, joint cavities and the bursae
o a viscous proteinaceous fluid lubricates the surfaces to
facilitate the sliding

Fluid Is Exchanged Between the Capillaries and the Potential

Spaces.
▪ The surface membrane of a potential space usually does not
offer significant 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
▪ Therefore, each potential space is in reality a large tissue space.
Consequently, 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.

▪ Proteins collect in the potential spaces because of leakage out
of the capillaries
▪ proteins are removed through lymphatics or other channels
and returned to the circulation

Edema Fluid in the Potential Spaces Is Called "Effusion."

▪ Effusion: edema fluid that collects in the potential space
adjacent to the subcutaneous tissues
o lymph blockage or any of the multiple abnormalities that
can cause excessive capillary filtration can cause effusion
o The abdominal cavity is especially prone to collect effusion
fluid, and in this instance, the effusion is called ascites. In
serious cases, 20 liters or more of ascitic fluid can
accumulate
o other potential spaces, such as the pleural cavity,
pericardial cavity, and joint spaces, become swollen when
there is generalized edema
o injury or local infection in any one of the cavities often
blocks the lymph drainage, causing isolated swelling in the
cavity