(The Microcirculation and the Lymphatic System (Capillary Fluid Exchange and Interstitial Fluid and and Lymph Flow pdf - The Circulation

especially in muscles and connective tissue. Note that the wall is composed of

typical endothelial cells in the capillary wall as found in most organs of the body,

Figure 16–2 shows the ultramicroscopic structure of

Structure of the Capillary Wall.

nutrients, end products of metabolism, hydrogen ions, and so forth—can cause direct

they serve. Therefore, the local conditions of the tissues—the concentrations of

however, some similar arrangement serves the same purposes. Most important, the

This typical arrangement of the capillary bed is not found in all parts of the body;

muscle.

in the arterioles, so that the venules still can contract considerably despite the weak

Yet it must be remembered that the pressure in the venules is much less than that

The venules are larger than the arterioles and have a much weaker muscular coat.

This sphincter can open and close the entrance to the capillary.

precapillary sphincter.

muscle fiber usually encircles the capillary. This is called the

At the point where each true capillary originates from a metarteriole, a smooth

16–1 by the black dots on the sides of the metarteriole.

smooth muscle fibers encircle the vessel at intermittent points, as shown in Figure

metarterioles (the terminal arterioles) do not have a continuous muscular coat, but

The arterioles are highly muscular, and their diameters can change manyfold. The

where they supply blood to the capillaries.

branch two to five times, reaching diameters of 5 to 9 micrometers at their ends

have internal diameters of only 10 to 15 micrometers. Then the arterioles themselves

arterioles,

needs. In general, each nutrient artery entering an organ branches six to eight times

The microcirculation of each organ is organized specifically to serve that organ’s

Capillary System

Structure of the Microcirculation and

tional cell of the body is more than 20 to 30 micrometers away from a capillary.

eighth the surface area of a football field). Indeed, it is rare that any single func-

The peripheral circulation of the whole body has about 10 billion capillaries

highly permeable endothelial cells. Therefore, water, cell nutrients, and cell

The walls of the capillaries are extremely thin, constructed of single-layer,

in relation to its individual needs, a subject that is

tissue, in most instances, controls its own blood flow

control the diameters of the arterioles. Thus, each

tissue area, and local conditions in the tissues in turn

The small arterioles control blood flow to each

nutrients to the tissues and removal of cell excreta

occurs in the microcirculation: this is

The most purposeful function of the circulation

and Lymph Flow

Fluid Exchange, Interstitial Fluid,

Lymphatic System: Capillary

The Microcirculation and the

181

transport of

discussed in detail in Chapter 17.

excreta can all interchange quickly and easily between the tissues and the cir-
culating blood.

with a total surface area estimated to be 500 to 700 square meters (about one-

before the arteries become small enough to be called

which generally

metarterioles and the precapillary sphincters are in close contact with the tissues

effects on the vessels in controlling local blood flow in each small tissue area.

in the tissues. When

oxygen

The most important factor

Regulation of Vasomotion.

intermittency is the phenomenon called

and off every few seconds or minutes. The cause of this

capillaries. Instead, it flows intermittently, turning on

Capillaries—Vasomotion

clefts between the endothelial cells.

cells, so that tremendous amounts of very small

, numerous

4. In the

muscles and those of the liver.

3. The pores of the

blood into the liver tissues.

including the plasma proteins, can pass from the

the capillary endothelial cells are wide open, so

, the opposite is true. The clefts between

2. In the

out of the brain tissues.

water, oxygen, and carbon dioxide to pass into or

endothelial cells are mainly “tight” junctions that

, the junctions between the capillary

1. In the

of the organs. Some of these characteristics are as

The “pores” in the capillaries of some organs

Special Types of “Pores” Occur in the Capillaries of Certain

transport are quantitatively of little importance.

However, careful measurements in laboratory animals

cell, which is demonstrated to the right in Figure 16–2.

vesicular channels

through the endothelial cell. It also has been postu-

or extracellular fluid. They can then move slowly

These form at one

plasmalemmal vesicles.

intercellular clefts.

rior of the capillaries through these “slit-pores,” the

motion of water molecules as well as most water-

the capillary wall. Nevertheless, the rate of thermal

the edges of the endothelial cells, they usually repre-

protein molecule.

cleft. The cleft normally has a uniform spacing with a

that hold the endothelial cells together, but between

adjacent endothelial cells. Each cleft is interrupted

which is the thin-slit, curving

interior of the capillary with the exterior. One of these

Studying Figure 16–2,

“Pores” in the Capillary Membrane.

diameter of the capillary is 4 to 9 micrometers, barely

illary wall is only about 0.5 micrometer. The internal

outside of the capillary. The total thickness of the cap-

182

Unit IV

The Circulation

a unicellular layer of endothelial cells and is sur-
rounded by a very thin basement membrane on the

large enough for red blood cells and other blood cells
to squeeze through.

one sees two very small passageways connecting the

is an intercellular cleft,
channel that lies at the bottom of the figure between

periodically by short ridges of protein attachments

these ridges fluid can percolate freely through the

width of about 6 to 7 nanometers (60 to 70 angstroms),
slightly smaller than the diameter of an albumin

Because the intercellular clefts are located only at

sent no more than 1/1000 of the total surface area of

soluble ions and small solutes is so rapid that all of
these diffuse with ease between the interior and exte-

Also present in the endothelial cells are many

minute
surface of the cell by imbibing small packets of plasma

lated that some of these vesicles coalesce to form

all the way through the endothelial

probably have proved that these vesicular forms of

Organs.

have special characteristics to meet the peculiar needs

follows:

brain

allow only extremely small molecules such as

liver

that almost all dissolved substances of the plasma,

gastrointestinal capillary

membranes are midway between those of the

glomerular tufts of the kidney

small oval windows called fenestrae penetrate all
the way through the middle of the endothelial

molecular and ionic substances (but not the large
molecules of the plasma proteins) can filter through
the glomeruli without having to pass through the

Flow of Blood in the

Blood usually does not flow continuously through the

vasomotion,

which means intermittent contraction of the metarte-
rioles and precapillary sphincters (and sometimes
even the very small arterioles as well).

found thus far to affect the degree of opening and
closing of the metarterioles and precapillary sphinc-
ters is the concentration of

Preferential channel

Metarteriole

Arteriole

Venule

Precapillary
sphincter

True capillaries

Jr., Foundation, 1950.)

BW: Factors Regulating Blood Pressure. New York: Josiah Macy,

Structure of the mesenteric capillary bed. (Redrawn from Zweifach

Figure 16–1

Endothelial

cell

Plasmalemmal

vesicles

Vesicular

channel??

Basement
membrane

Intercellular

cleft

that most water-soluble substances diffuse through the capillary

intercellular cleft

Structure of the capillary wall. Note especially the

Figure 16–2

at the junction between adjacent endothelial cells; it is believed

membrane along the clefts.

Therefore, the permeability of the capillary pores for

ions, glucose, and urea, have intermediate diameters.

pores. Other substances, such as sodium ions, chloride

pores. Conversely, the diameters of plasma protein

ter of the water molecule, which is the smallest

pores, 6 to 7 nanometers, is about 20 times the diame-

The width of the capillary intercellular cleft-

capillary.

That is, the water of the plasma is exchanged with

which plasma itself flows linearly along the capillary

rate at which water molecules diffuse through the cap-

of the rapidity with which these substances diffuse,

stances through these cleft-pores. To give one an idea

tremendous diffusion of water and water-soluble sub-

intercellular clefts between the endothelial cells, the

. Despite the fact that not more than 1/1000 of

, and

chloride ions

themselves,

the endothelial cells; such substances include

Through Intercellular “Pores” in the Capillary Membrane.

Water-Soluble, Non-Lipid-Soluble Substances Diffuse Only

go only through the pores.

substances, such as sodium ions and glucose that can

meate all areas of the capillary membrane, their rates

. Because these substances can per-

carbon dioxide

oxygen

through the pores. Such substances include

lipid soluble, it can diffuse directly through the cell

Membranes of the Capillary Endothelium.

tion and then another, bouncing randomly in every

, the

forth through the capillary wall, providing continual

lumen of the capillary, tremendous numbers of water

process, showing that as the blood flows along the

. Figure 16–3 demonstrates this

Exchange of Water, Nutrients,

response to local conditions in the tissues.

individual capillaries, each operating intermittently in

tions are, in reality, the functions of literally billions of

chapter, we will be concerned with these averages,

surrounding interstitial fluid. In the remainder of this

within the capillaries, and an

each tissue capillary bed, an

average rate of blood flow

That is, there is an

is intermittent, so many capillaries are present in the

Average Function of the

ple other factors that control local tissue blood flow, is

nutrients) to the tissues. This effect, along with multi-

lasts longer, thereby allowing the capillary blood to

more often, and the duration of each period of flow

The Microcirculation and the Lymphatic System

Chapter 16

183

the rate of oxygen usage by the tissue is great so that
tissue oxygen concentration decreases below normal,
the intermittent periods of capillary blood flow occur

carry increased quantities of oxygen (as well as other

discussed in Chapter 17.

Capillary System

Despite the fact that blood flow through each capillary

tissues that their overall function becomes averaged.

through

average capillary pressure

average rate of transfer of

substances between the blood of the capillaries and the

although one must remember that the average func-

and Other Substances
Between the Blood and
Interstitial Fluid

Diffusion Through the
Capillary Membrane

By far the most important means by which substances
are transferred between the plasma and the interstitial
fluid is diffusion

molecules and dissolved particles diffuse back and

mixing between the interstitial fluid and the plasma.
Diffusion results from thermal motion of the water
molecules and dissolved substances in the fluid
different molecules and ions moving first in one direc-

direction.

Lipid-Soluble Substances Can Diffuse Directly Through the Cell

If a substance is

membranes of the capillary without having to go

and

of transport through the capillary membrane are
many times faster than the rates for lipid-insoluble

Many substances needed by the tissues are soluble in
water but cannot pass through the lipid membranes of

water

molecules

sodium ions,

glucose
the surface area of the capillaries is represented by the

velocity of thermal molecular motion in the clefts is so
great that even this small area is sufficient to allow

the

illary membrane is about 80 times as great as the rate at

the water of the interstitial fluid 80 times before the
plasma can flow the entire distance through the

Effect of Molecular Size on Passage Through the
Pores.

molecule that normally passes through the capillary

molecules are slightly greater than the width of the

Arterial end

Venous end

Blood capillary

Lymphatic

capillary

the capillary and interstitial fluid spaces.

Diffusion of fluid molecules and dissolved substances between

Figure 16–3

protein. These molecules are so thin that they can

of the tissues. The proteoglycan filaments, however, are

tances in the interstitium. They are extremely strong

The collagen fiber bundles extend long dis-

ments.

16–4. It contains two major types of solid structures:

The structure of the interstitium is shown in Figure

The fluid in these spaces is the

sists of spaces between cells, which collectively are

during very active states of the body.

blood, yet this slight difference causes enough oxygen

the plasma and interstitial fluid. For instance, the con-

The rates of diffusion through the capillary mem-

the tissues.

than in the blood, which causes excess carbon dioxide

from the blood toward the tissues. Conversely, the con-

Therefore, large quantities of oxygen normally move

instance, the concentration of oxygen in capillary

stance in one direction through the membrane. For

membrane, the greater the net movement of the sub-

between the two sides of the membrane. That is, the

The “net” rate of diffu-

Through the Capillary Membrane.

of large quantities of fluid for formation of urine.

parenchymal cells, and the kidneys to allow filtration

liver, for instance—require greater degrees of capillary

this text, it should become clear why some tissues—the

organs. When we study these different organs later in

permeabilities are very slight, as in other tissues and

true for the plasma proteins; for these, the capillary

permeability of the muscle capillaries, but this is not

Also, the permeability of the renal glomerular mem-

walls, almost as easily as water and other substances.

ferences in their permeabilities. For instance, the mem-

The capillaries in different tissues have extreme dif-

for water molecules.

albumin molecules is very, very slight, only 1/1000 that

for water molecules, whereas the permeability for

monly encountered, demonstrating, for instance, that

Table 16–1 gives the relative permeabilities of the

lar diameters.

184

Unit IV

The Circulation

different substances varies according to their molecu-

capillary pores in skeletal muscle for substances com-

the permeability for glucose molecules is 0.6 times that

A word of caution must be issued at this point.

brane of the liver capillary sinusoids is so permeable
that even plasma proteins pass freely through these

brane for water and electrolytes is about 500 times the

permeability than others to transfer tremendous
amounts of nutrients between the blood and liver

Effect of Concentration Difference on Net Rate of Diffusion

sion of a substance through any membrane is propor-
tional to the concentration difference of the substance

greater the difference between the concentrations of
any given substance on the two sides of the capillary

blood is normally greater than in the interstitial fluid.

centration of carbon dioxide is greater in the tissues

to move into the blood and to be carried away from

branes of most nutritionally important substances are
so great that only slight concentration differences
suffice to cause more than adequate transport between

centration of oxygen in the interstitial fluid immedi-
ately outside the capillary is no more than a few per
cent less than its concentration in the plasma of the

to move from the blood into the interstitial spaces to
provide all the oxygen required for tissue metabolism,
often as much as several liters of oxygen per minute

The Interstitium and
Interstitial Fluid

About one sixth of the total volume of the body con-

called the interstitium.
interstitial fluid.

(1) collagen fiber bundles and (2) proteoglycan fila-

and therefore provide most of the tensional strength

extremely thin coiled or twisted molecules composed
of about 98 per cent hyaluronic acid and 2 per cent

never be seen with a light microscope and are difficult

Relative Permeability of Skeletal Muscle Capillary Pores to

Table 16–1

Albumin

69,000

0.001

Hemoglobin

68,000

0.01

Myoglobin

17,600

0.03

Inulin

5,000

0.2

Sucrose

342

0.4

Glucose

180

0.6

Urea

0.8

NaCl

58.5

0.96

Water

1.00

Substance

Molecular Weight

Permeability

Different-Sized Molecules

Physiol Rev 33:387, 1953.

Data from Pappenheimer JR: Passage of molecules through capillary walls.

Free fluid
vesicles

Rivulets
of free
fluid

Proteoglycan

filaments

Collagen fiber

bundles

Capillary

occasionally also occur.

vesicles and small amounts of free fluid in the form of rivulets

where in the spaces between the collagen fiber bundles. Free fluid

Structure of the interstitium. Proteoglycan filaments are every-

Figure 16–4

organs. The rate of fluid filtration in a tissue is also

normal conditions, resulting in a net filtration of fluid

As discussed later, the NFP is slightly positive under

tial spaces into the capillaries. The net filtration pres-

from the intersti-

capillaries. If the sum of the Starling forces is negative,

is positive, there will be a net

If the sum of these forces, the

through the capillary membrane.

outward

4. The

through the capillary membrane.

inward

p), which tends to cause osmosis of fluid

3. The capillary

Pif is negative.

inward

(Pif), which tends

2. The

through the capillary membrane.

outward

(Pc), which tends to force

1. The

who first demonstrated their importance, are:

called “Starling forces” in honor of the physiologist

stitial fluid or in the opposite direction. These forces,

Figure

Fluid Movement Through the Capillary Membrane.

Four Primary Hydrostatic and Colloid Osmotic Forces Determine

interstitial spaces. In the remainder of this chapter, we

, which

spaces.

into the blood. This osmotic pressure exerted by

colloid osmotic pressure

capillary pores into the interstitial spaces. Conversely,

The hydrostatic pressure in the capillaries tends to

Capillary Filtration Coefficient

Osmotic Pressures, and

by Hydrostatic and Colloid

Capillaries Is Determined

Fluid Filtration Across

fluid independent of the proteoglycan filaments.

edema, these small pockets

is slight, usually much less than 1 per cent. Conversely,

The amount of “free” fluid present in

faces of cells.

through the interstitium in the small rivulets, usually

into the circulating blood, it often can be seen to flow

and therefore can flow freely. When a dye is injected

are also present, which

rivulets of “free” fluid

the tissue gel, occasionally small

excreta, oxygen, carbon dioxide, and so forth.

electrolytes, small molecular weight nutrients, cellular

cells, this diffusion allows rapid transport through the

cent as rapidly as it does through free fluid. For the

large numbers of molecules moving together.

to another by kinetic, thermal motion rather than by

that is, it moves molecule by molecule from one place

it mainly diffuses

tissue gel. Instead,

difficult for fluid to flow

ments, it is

proteoglycan filaments. This combination of proteo-

pores of the capillaries with ease. The interstitial fluid

derived by filtration and diffusion from the capillaries.

The fluid in the interstitium is

aments aptly described as a “brush pile.”

Nevertheless, they form a mat of very fine reticular fil-

to demonstrate even with the electron microscope.

The Microcirculation and the Lymphatic System

Chapter 16

185

“Gel” in the Interstitium.

It contains almost the same constituents as plasma
except for much lower concentrations of proteins
because proteins do not pass outward through the

is entrapped mainly in the minute spaces among the

glycan filaments and fluid entrapped within them has
the characteristics of a gel and therefore is called tissue
gel.

Because of the large number of proteoglycan fila-

easily through the

through the gel;

Diffusion through the gel occurs about 95 to 99 per

short distances between the capillaries and the tissue

interstitium not only of water molecules but also of

“Free” Fluid in the Interstitium.

Although almost all the

fluid in the interstitium normally is entrapped within

and small free fluid vesicles
means fluid that is free of the proteoglycan molecules

coursing along the surfaces of collagen fibers or sur-

normal tissues

when the tissues develop
and rivulets of free fluid expand tremendously until one
half or more of the edema fluid becomes freely flowing

force fluid and its dissolved substances through the

osmotic pressure caused by the plasma proteins
(called

) tends to cause fluid

movement by osmosis from the interstitial spaces

the plasma proteins normally prevents significant loss

of fluid volume from the blood into the interstitial

Also important is the lymphatic system

returns to the circulation the small amounts of excess
protein and fluid that leak from the blood into the

discuss the mechanisms that control capillary filtration
and lymph flow function together to regulate the
respective volumes of the plasma and the interstitial
fluid.

16–5 shows the four primary forces that determine
whether fluid will move out of the blood into the inter-

capillary pressure

fluid

interstitial fluid pressure

to force fluid

through the capillary

membrane when Pif is positive but outward when

plasma colloid osmotic pressure

(

interstitial fluid colloid osmotic pressure (

Pif),

which tends to cause osmosis of fluid

net filtration pressure,

fluid filtration across the

there will be a net fluid absorption

sure (NFP) is calculated as:

across the capillaries into the interstitial space in most

determined by the number and size of the pores in
each capillary as well as the number of capillaries in

Pif

Capillary
pressure

(Pc)

Plasma colloid

osmotic pressure

(

Interstitial

fluid pressure

(Pif)

Interstitial fluid

colloid osmotic pressure

(

if)

inward through the membrane pores.

capillary membrane, tending to move fluid either outward or

Fluid pressure and colloid osmotic pressure forces operate at the

Figure 16–5

maneuvers; otherwise, either

at this same level of 17 mm Hg throughout these

Therefore, the capillary pressure must have remained

venous lines meet each other at a value of 17 mm Hg.

nullify all weight changes are shown. The arterial and

gure, the

and (2) increasing the venous pressure.

words, the capillary pressure is kept constant while

effect of decreasing the arterial pressure. In other

To prevent this weight decrease, the venous pressure

gut wall and makes the weight of the gut decrease. This

arterial pressure is decreased, the resulting decrease in

through the blood vessels of the gut wall. When the

one arm of a gravimetric balance. Blood is perfused

pressure. This

Figure 16

Capillary Pressure.

Hg in the middle.

10 to 15 mm Hg in the venous ends, and about 25 mm

30 to 40 mm Hg in the arterial ends of the capillaries,

humans. These measurements have given pressures of

micromanometer system. Using this method, capillary

illary, and the pressure is measured by an appropriate

measure pressure in a capillary by cannulation, a

Micropipette Method for Measuring Capillary Pressure.

averaging about 17 mm Hg.

, which has given a capillary pressure

mm Hg, and (2)

, which has

mate the capillary hydrostatic pressure: (1)

Two experimental methods have been used to esti-

The rate of capillary

ltration pressure.

NFP and is usually expressed as ml/min per mm Hg

). The K

owing. These factors are usually

186

Unit IV

The Circulation

which blood is fl
expressed together as the capillary filtration coefficient
(K

is therefore a measure of the capacity of

the capillary membranes to filter water for a given

net fi

fluid filtration is therefore

determined as:

In the following sections we discuss in detail each

of the forces that determine the rate of capillary fluid
filtration.

Capillary Hydrostatic Pressure

direct

micropipette cannulation of the capillaries
given an average mean capillary pressure of about 25

indirect functional measurement of the

capillary pressure

microscopic glass pipette is thrust directly into the cap-

pressures have been measured in capillaries of
exposed tissues of animals and in large capillary loops
of the eponychium at the base of the fingernail in

Isogravimetric Method for Indirectly Measuring “Functional”

–6 demonstrates an iso-

gravimetric method for indirectly estimating capillary

figure shows a section of gut held up by

capillary pressure allows the osmotic pressure of the
plasma proteins to cause absorption of fluid out of the

immediately causes displacement of the balance arm.

is increased an amount sufficient to overcome the

simultaneously (1) decreasing the arterial pressure

In the graph in the lower part of the fi

changes in arterial and venous pressures that exactly

filtration or absorption of

Filtration

NFP

give higher pressure values. The most important

averages about 17 mm Hg.

the isogravimetric method. Therefore, one is justi

is the normal state, the average functional capillary

out of the capillaries. Because such a balance of forces

same capillary pressure. However, the isogravimetric

Why Is the Functional Capillary Pressure Lower than Capillary

pressure is measured to be about 17 mm Hg.

Thus, in a roundabout way, the

fluid through the capillary walls would have occurred.

“functional” capillary

Pressure Measured by the Micropipette Method?

It is clear

that the aforementioned two methods do not give the

method determines the capillary pressure that exactly
balances all the forces tending to move fluid into or

pressure must be close to the pressure measured by

fied

in believing that the true functional capillary pressure

It is easy to explain why the cannulation methods

reason is that these measurements usually are made
in capillaries whose arterial ends are open and when

100

Arterial pressure

Gut

100

Pressure 40

Capillary pressure

= 17 mm Hg

Arterial

Venous

Arterial pressure – venous pressure

Venous pressure

Isogravimetric method for measuring capillary pressure.

Figure 16–6

pressure. The importance of these observations is

cause no more than about 2 mm Hg of positive

interstitial space, when injected into these areas,

scrotum. Amounts of

the lower eyelid, in the axillary space, and in the

into loose subcutaneous tissues, such as beneath

2. Less than 1 mm Hg of positive pressure is

the skin back into the concavity.

pull it away from the concavity. Nevertheless,

attempts to shorten, with the result that it tends to

collect underneath the graft. Also, the skin

removal of the eye, before the skin becomes

of the body, such as in an eye socket after

1. When a skin graft is placed on a concave surface

uid pressure was always positive. Some of the per-

The concept that the interstitial

Is the True Interstitial Fluid Pressure in Loose

tissue.

which is considered to be zero pressure, one might for-

pressure exerted on the skin is atmospheric pressure,

6 mm Hg. Thus, if one remembers that the

13 mm Hg, whereas the

Hg. In the kidneys, the capsular pressure surrounding

6 mm

10 mm Hg, whereas the

their encasements. For instance, the cerebrospinal

pressures are usually positive. However, these intersti-

method used for measurement, the interstitial

around the eye. In most of these, regardless of the

brous sheaths around the muscles, and the sclera

brous capsule around the kidney, the

brain, the strong

encasements, such as the cranial vault around the

Interstitial Fluid Pressures in Tightly

3 mm Hg.

negative, usually measuring

usual manometric means. Pressures measured by this

uid pressure into the Te

protruding from its end. The cotton

tissue a small Te

Measurement of Interstitial Free Fluid Pressure by Means of a

measured by the micropipette in Figure 16-7.

2 mm Hg

6 mm Hg, but with smaller capsules,

slightly less than atmospheric pressure.

tissues, such as skin, that are

2 mm Hg, giving average

ment for making such measurements, more recent pres-

slightly positive. With experience and improved equip-

2 mm Hg but were usually

The

interstitium. Therefore, the pressure that is measured is

of the micropipette is about 1 micrometer in diameter,

uid pressure. The tip

The same type of micropipette used for

cotton wick inserted into the tissue.

capsules, and (3) measurement of the pressure from a

nulation of the tissues with a micropipette, (2) meas-

. The

ters of mercury less than atmospheric pressure, that is,

uid pressure, and each of these gives slightly differ-

As is true for the measurement of capillary pressure,

the functional capillary pressure to a lower value.

rial capillaries. Both of these effects further decrease

the venules than to the arterioles. Second, the venous

nulation. First, there are far more capillaries nearer to

There are two other reasons why the functional cap-

pressure in the arterial ends.

over a period of time, one would expect the

laries, about 10 mm Hg. Therefore, when averaged

of the vasomotion cycle. When closed, the pressure in

owing into the capillary. However, it

The Microcirculation and the Lymphatic System

Chapter 16

187

blood is actively fl
should be recalled from the earlier discussion of cap-
illary vasomotion that the metarterioles and precapil-
lary sphincters normally are closed during a large part

the capillaries beyond the closures should be almost
equal to the pressure at the venous ends of the capil-

functional

mean capillary pressure to be much nearer to the pres-
sure in the venous ends of the capillaries than to the

illary pressure is less than the values measured by can-

capillaries are several times as permeable as the arte-

Interstitial Fluid Hydrostatic Pressure

there are several methods for measuring interstitial
fl
ent values but usually values that are a few millime-

values called negative interstitial fluid pressure
methods most widely used have been (1) direct can-

urement of the pressure from implanted perforated

Measurement of Interstitial Fluid Pressure Using the
Micropipette.

measuring capillary pressure can also be used in some
tissues for measuring interstitial fl

but even this is 20 or more times larger than the sizes
of the spaces between the proteoglycan filaments of the

probably the pressure in a free fluid pocket.

first pressures measured using the micropipette

method ranged from

-1 to +

sures have averaged about

pressure values in loose

Measurement of Interstitial Free Fluid Pressure in Implanted Per-
forated Hollow Capsules.

Interstitial free fluid pressure

measured by this method when using 2-centimeter
diameter capsules in normal loose subcutaneous tissue
averages about

the values are not greatly different from the

Cotton Wick.

Still another method is to insert into a

flon tube with about eight cotton fibers

fibers form a “wick”

that makes excellent contact with the tissue fluids and
transmits interstitial fl

flon tube:

the pressure can then be measured from the tube by

technique in loose subcutaneous tissue also have been

-1 to -

Encased Tissues

Some tissues of the body are surrounded by tight

fluid

tial fluid pressures almost invariably are still less than
the pressures exerted on the outsides of the tissues by

fluid

pressure surrounding the brain of an animal lying on
its side averages about

brain

interstitial fluid pressure averages about

+4 to +

the kidney averages about

reported renal interstitial fluid pressures have averaged
about

mulate a general rule that the normal interstitial fluid
pressure is usually several millimeters of mercury neg-
ative with respect to the pressure that surrounds each

Subcutaneous Tissue Subatmospheric?

fluid pressure is sub-

atmospheric in many if not most tissues of the body
began with clinical observations that could not be
explained by the previously held concept that intersti-
tial fl
tinent observations are the following:

attached to the sublying socket, fluid tends to

some negative force underneath the skin causes
absorption of the fluid and usually literally pulls

required to inject tremendous volumes of fluid

fluid calculated to be more

than 100 times the amount of fluid normally in the

that they show that such tissues do not have

mass, the following chart gives both the relative mass

rather than by the mass of these molecules. Therefore,

as 1 gram of albumin, and 1 gram of

brinogen, 400,000. Thus,

69,000; globulins, 140,000; and

tains albumin, with an average molecular weight of

The plasma proteins are a mixture that con-

caused by sodium, potassium, and the other cations

that is, extra osmotic pressure

molecular effects of the dissolved protein and 9 mm by

averages about 28 mm Hg; 19 mm of this is caused by

The

Normal Values for Plasma Colloid Osmotic Pressure.

The

oncotic pressure.

that which occurs at the cell membrane, it is called

membrane. To distinguish this osmotic pressure from

through the capillary pores, it is the proteins of the

able membrane exert osmotic pressure. Because the

basic discussion of osmotic pressure in Chapter 4, it

spaces.

This overall process creates the slight negative pres-

uid enters the terminal lymphatic capillaries,

and other matter from the tissue spaces. Normally,

uid, excess protein molecules, debris,

The lymphatic system is a

uid pressure.

The lymphatic system is discussed later in the chapter,

Fluid Pressure

Pumping by the Lymphatic System Is the

3 mm Hg.

tissue is slightly less subatmospheric, averaging about

uid pressure, there currently

Pressure in Loose Subcutaneous Tissue.

Summary—An Average Value for Negative Interstitial Fluid

pressure.

uid from the tissue spaces. It

surrounding tissue space, or (3) when a highly

or decreased, (2) when

dynamic changes in this pressure. The changes are

4. The implanted capsule for measuring the

6 mm Hg

Joint synovial spaces:

8 mm Hg

have been measured have been negative. Some of

uids, the pressures that

3. In most natural cavities of the body where there

uid pressure system, must be available

uid. Therefore, some other mechanism, such as a

188

Unit IV

The Circulation

strong fibers that can prevent the accumulation of
fl
negative fl
to prevent such fluid accumulation.

is free fluid in dynamic equilibrium with the
surrounding interstitial fl

these are the following:

Intrapleural space:

4 to

Epidural space:

4 to

interstitial fluid pressure can be used to record

approximately those that one would calculate to
occur (1) when the arterial pressure is increased

fluid is injected into the

concentrated colloid osmotic agent is injected into
the blood to absorb fl
is not likely that these dynamic changes could be
recorded this accurately unless the capsule
pressure closely approximated the true interstitial

Although the

aforementioned different methods give slightly differ-
ent values for interstitial fl
is a general belief among most physiologists that the
true interstitial fluid pressure in loose subcutaneous

Basic Cause of the Negative Interstitial

but we need to understand here the basic role that this
system plays in determining interstitial fl

“scavenger” system that

removes excess fl

when fl
the lymph vessel walls automatically contract for a few
seconds and pump the fluid into the blood circulation.

sure that has been measured for fluid in the interstitial

Plasma Colloid Osmotic Pressure

Proteins in the Plasma Cause Colloid Osmotic Pressure.

In the

was pointed out that only those molecules or ions that
fail to pass through the pores of a semiperme-

proteins are the only dissolved constituents in the
plasma and interstitial fluids that do not readily pass

plasma and interstitial fluids that are responsible for
the osmotic pressures on the two sides of the capillary

either colloid osmotic pressure or
term “colloid” osmotic pressure is derived from the
fact that a protein solution resembles a colloidal solu-
tion despite the fact that it is actually a true molecu-
lar solution.

colloid osmotic pressure of normal human plasma

the Donnan effect—

held in the plasma by the proteins.

Effect of the Different Plasma Proteins on Colloid Osmotic
Pressure.

1 gram of globulin contains only half as many molecules

fibrinogen contains

only one sixth as many molecules as 1 gram of albumin.
It should be recalled from the discussion of osmotic
pressure in Chapter 4 that osmotic pressure is deter-
mined by the number of molecules dissolved in a fluid

when corrected for number of molecules rather than

concentrations (g/dl) of the different types of proteins
in normal plasma and their respective contributions to
the total plasma colloid osmotic pressure (

Pp).

Globulins

2.5

6.0

Albumin

4.5

21.8

p (mm Hg)

g/dl

Fibrinogen

0.3

0.2

the total quantity of protein in the plasma itself, but

The total quantity of protein in the entire 12 liters

interstitial spaces.

not true of all the pores. Therefore, small amounts of

than the molecular sizes of the plasma proteins, this is

uid dynamics, it is mainly

brinogen. Therefore, from the point of view

tion, 20 per cent from the globulins, and almost none

Thus, about 80 per cent of the total colloid osmotic

Total

7.3

28.0

pressure of the plasma results from the albumin frac-

from the fi
of capillary and tissue fl
albumin that is important.

Interstitial Fluid Colloid
Osmotic Pressure

Although the size of the usual capillary pore is smaller

plasma proteins do leak through the pores into the

of interstitial fluid of the body is slightly greater than

of the capillary. This calculates to be 17.3 mm Hg.

rial and venous capillaries are averaged to calculate

ling equilibrium. For this chart, the pressures in the arte-

The following chart shows the principles of the Star-

that is eventually returned by way of the lymphatics.

circulation by absorption. The slight disequilibrium

exists at the capillary membrane. That is, the amount

under normal conditions, a state of near-equilibrium

E. H. Starling pointed out over a century ago that

The remaining one tenth

the capillaries to be reabsorbed at the venous ends.

The reabsorption pressure causes about nine tenths

capillaries, so that less reabsorption pressure is

ends, but remember that the venous capillaries are

capillaries. This reabsorption pressure is considerably

reabsorption, 21 mm Hg. The difference, 7 mm Hg, is

capillary, 28 mm Hg, is greater than that opposing

Thus, the force that causes

The low blood pressure at the venous end of the cap-

Analysis of Reabsorption at the Venous End of the Capillary.

through the capillaries.

average, about 1/200 of the plasma in the

ltration pressure causes, on the

This 13 mm Hg

lary pores.

Hg, tending to move

of 13 mm

Thus, the summation of forces at the arterial end of

The approximate average forces operative

the Capillary.

are as follows.

illaries to the venous ends. The dynamics of this

ies. Thus, a small amount of

out of the capillaries at their arterial ends, but at their

venous ends. Because of this difference,

of the capillaries is 15 to 25 mm Hg greater than at the

The average capillary pressure at the arterial ends

discussed, it is possible to put all these together to

Exchange of Fluid Volume Through

this concentration of proteins is about 8 mm Hg.

or about 3 g/dl. Quantitatively, one

plasma, the average protein

The Microcirculation and the Lymphatic System

Chapter 16

189

because this volume is four times the volume of

concentration of the inter-

stitial fluid is usually only 40 per cent of that in plasma,

finds that the

average interstitial fluid colloid osmotic pressure for

the Capillary Membrane

Now that the different factors affecting fluid move-
ment through the capillary membrane have been

see how the capillary system maintains normal fluid
volume distribution between the plasma and the inter-
stitial fluid.

fluid “filters”

venous ends fluid is reabsorbed back into the capillar-

fluid actually “flows”

through the tissues from the arterial ends of the cap-

flow

Analysis of the Forces Causing Filtration at the Arterial End of

at the arterial end of the capillary that cause movement
through the capillary membrane are shown as follows:

the capillary shows a net filtration pressure

fluid outward through the capil-

flowing blood

to filter out of the arterial ends of the capillaries into
the interstitial spaces each time the blood passes

illary changes the balance of forces in favor of absorp-
tion as follows:

fluid to move into the

the net reabsorption pressure at the venous ends of the

less than the filtration pressure at the capillary arterial

more numerous and more permeable than the arterial

required to cause inward movement of fluid.

of the fluid that has filtered out of the arterial ends of

flows into the lymph vessels

and returns to the circulating blood.

Starling Equilibrium for
Capillary Exchange

of fluid filtering outward from the arterial ends of cap-
illaries equals almost exactly the fluid returned to the

that does occur accounts for the small amount of fluid

mean functional capillary pressure for the entire length

uid pressure

Capillary pressure (arterial end of capillary)

mm Hg

Forces tending to move fluid outward:

Negative interstitial free fl

total outward force

uid colloid osmotic pressure

Interstitial fl

Forces tending to move fluid inward:

Outward

total inward force

Plasma colloid osmotic pressure

28
28

Summation of forces:

Inward

)

at arterial end

net outward force (

Forces tending to move fluid inward:

mm Hg

uid pressure

Capillary pressure (venous end of capillary)

Forces tending to move fluid outward:

total inward force

Plasma colloid osmotic pressure

Negative interstitial free fl

Inward

total outward force

uid colloid osmotic pressure

Interstitial fl

Summation of forces:

Outward

net inward force

uid pressure

3.0

Mean capillary pressure

17.3

mm Hg

Mean forces tending to move fluid outward:

Negative interstitial free fl

Mean force tending to move fluid inward:

total outward force

uid colloid osmotic pressure

8.0

Interstitial fl

28.3

Outward

28.3

total inward force

Plasma colloid osmotic pressure

28.0

Summation of mean forces:

Inward

28.0

net outward force

0.3

Terminal Lymphatic Capillaries and Their Permeability.

(much smaller than the thoracic duct), which

right arm, and parts of the right thorax enters the

Lymph from the right side of the neck and head, the

before it empties into the veins.

Lymph from the left side of the head, the left arm, and

clavian vein, as shown in Figure 16

case of the brain, into the cerebrospinal

tually empties either into lymphatic vessels or, in the

ow; this

of muscles, and the bones. But, even these tissues have

of the skin, the central nervous system, the endomysium

spaces. The exceptions include the super

Lymph Channels of the Body

which we would die within about 24 hours.

laries. This return of proteins to the blood from the

from the tissue spaces, neither of which can be

spaces into the blood. Most important, the lymphatics

The lymphatic system represents an accessory route

Lymphatic System

These effects of imbalance at the capillary membrane

uid volume.

ltration, and the blood volume will

Conversely, if the capillary pressure falls very low,

to accumulate in the interstitial spaces, and edema will

lymphatics to carry away. As a result,

system, an amount that is 2 to 5 times too much for the

stitial spaces as normally occurs. To prevent accumu-

sure from 0.3 mm Hg to 20.3 mm Hg, which results in

tissue spaces rises. Thus, a 20 mm Hg rise in mean cap-

If the mean capillary pressure rises above 17 mm Hg,

at the Capillary Membrane

Effect of Abnormal Imbalance of Forces

6 g/dl.

taneous tissue, 2 g/dl; in intestine, 4 g/dl; and in liver,

uid of muscles is about 1.5 g/dl; in subcu-

greatly as well. The concentration of protein in the

or wide open. By the same token, the permeation

in the intestine, and extreme in the liver and glomeru-

muscle, moderately large in subcutaneous tissue, large

different tissues. It is very small in both brain and

abilities of the capillary systems in different tissues,

tissue. But, because of extreme differences in perme-

average tissue is about 0.01 ml/min/mm Hg/100 g of

of tissue. On this basis, the

The

mercury for the entire body. This is called the whole

of mercury imbalance, one

body of 2 ml/min. Expressing this for each millimeter

of 0.3 mm Hg causes net

In the above example, an average

about 2 milliliters per minute.

returned to the circulation through the lymphatics. The

, and it is the

spaces than reabsorption.This slight excess of

This slight imbalance of forces, 0.3 mm Hg, causes

28.3 mm Hg, and the total inward force, 28.0 mm Hg.

near-equilibrium between the total outward forces,

Thus, for the total capillary circulation, we

190

Unit IV

The Circulation

find a

slightly more filtration of fluid into the interstitial

filtration

is called net filtration

fluid that must be

normal rate of net filtration in the entire body is only

Filtration Coefficient.

net imbalance of forces at the capillary membranes

fluid filtration in the entire

finds a net filtration rate

of 6.67 milliliters of fluid per minute per millimeter of

body capillary filtration coefficient.

filtration coefficient can also be expressed for

separate parts of the body in terms of rate of filtration
per minute per millimeter of mercury per 100 grams

filtration coefficient of the

this coefficient varies more than 100-fold among the

lus of the kidney where the pores are either numerous

of proteins through the capillary membranes varies

interstitial fl

the net force tending to cause filtration of fluid into the

illary pressure causes an increase in net filtration pres-

68 times as much net filtration of fluid into the inter-

lation of excess fluid in these spaces would require 68
times the normal flow of fluid into the lymphatic

fluid will begin

result.

net reabsorption of fluid into the capillaries will occur
instead of net fi
increase at the expense of the interstitial fl

in relation to the development of different kinds of
edema are discussed in Chapter 25.

through which fluid can flow from the interstitial

can carry proteins and large particulate matter away

removed by absorption directly into the blood capil-

interstitial spaces is an essential function without

Almost all tissues of the body have special lymph chan-
nels that drain excess fluid directly from the interstitial

ficial portions

minute interstitial channels called prelymphatics
through which interstitial fluid can fl

fluid even-

fluid and then

directly back into the blood.

Essentially all the lymph vessels from the lower part

of the body eventually empty into the thoracic duct,
which in turn empties into the blood venous system at
the juncture of the left internal jugular vein and left sub-

–8.

parts of the chest region also enters the thoracic duct

right

lymph duct
empties into the blood venous system at the juncture of
the right subclavian vein and internal jugular vein.

Most

of the fluid filtering from the arterial ends of blood

Fluid filled cavity

measure
pressure

Skin

Implanted

capsule

Blood

vessels

pressure.

Perforated capsule method for measuring interstitial fluid

FIGURE 16–7

the lymphatics. Therefore, lymph as it

Lymph is derived from interstitial

Formation of Lymph

Thus, the lymphatics have valves at the very tips of the

ap valve.

ow directly into the lymphatic capillary. But

along with its suspended particles, can push the valve

interior of the lymphatic capillary. Interstitial

inward, thus forming a minute valve that opens to the

junctions of adjacent endothelial cells, the edge of one

to the surrounding connective tissue. At the

anchoring fila-

9. This

Figure 16

structure of the lymphatic capillaries, demonstrated in

almost unimpeded. The reason for this is a special

cannot be absorbed from the tissues in any other way,

stances of high molecular weight, such as proteins,

The

this lymph is normally only 2 to 3 liters each day.

through the venous capillaries. The total quantity of all

but on the average, about 1/10 of the

The Microcirculation and the Lymphatic System

Chapter 16

191

capillaries flows among the cells and finally is reab-
sorbed back into the venous ends of the blood capil-
laries;

fluid

instead enters the lymphatic capillaries and returns to
the blood through the lymphatic system rather than

fluid that returns to the circulation by way of

the lymphatics is extremely important because sub-

although they can enter the lymphatic capillaries

–

figure shows the endothelial cells of

the lymphatic capillary attached by
ments

endothelial cell overlaps the edge of the adjacent cell

in such a way that the overlapping edge is free to flap

fluid,

open and fl
this fluid has difficulty leaving the capillary once it has
entered because any backflow closes the fl

terminal lymphatic capillaries as well as valves along
their larger vessels up to the point where they empty
into the blood circulation.

fluid that flows into

first enters the

terminal lymphatics has almost the same composition
as the interstitial fluid.

Cervical nodes

Sentinel node

Subclavian vein

R. lymphatic duct

Thoracic duct

Axillary nodes

Cisterna chyli

Abdominal nodes

Inguinal nodes

Peripheral lymphatics

Lymphatic system.

FIGURE 16–8

lymph channels; typical valves are shown in Figure

Valves exist in all

Lymphatic Pump Increases Lymph Flow.

plateau in Figure 16

This is illustrated by the upper level

ow rate.

factors balance each other almost exactly, so that

ow. At the higher pressures, these two

outside surfaces of the larger lymphatics, thus imped-

sures. This results from the fact that the increasing

than atmospheric pressure (greater than 0 mm Hg),

However, note in Figure 16

at the same time.

uid pressure, and lymph

volume, interstitial

into the interstitium, thus increasing interstitial

vessels are functioning normally. Such factors include

20-fold. Therefore, any factor that increases interstitial

6 mm Hg. Then, as the pressure rises to 0 mm

ow as measured in dog legs.

Figure

Effect of Interstitial Fluid Pressure on Lymph Flow.

per day.

each hour through other channels, making a total esti-

of a resting human, and approxi-

Rate of Lymph Flow

As the lymph passes through the lymph nodes, these

Finally, even large particles, such as bacteria, can

meal, thoracic duct lymph sometimes contains as much

food, as discussed in Chapter 65. Indeed, after a fatty

tract, especially for absorption of virtually all fats in

The lymphatic system is also one of the major routes

concentration of 3 to 5 g/dl.

lymph from all areas of the body, usually has a protein

tines, the thoracic duct lymph, which is a mixture of

high as 3 to 4 g/dl. Because about two thirds of all

protein concentration as high as 6 g/dl, and lymph

this value. Conversely, lymph formed in the liver has a

most tissues averages about 2 g/dl, and the protein con-

The protein concentration in the interstitial

192

Unit IV

The Circulation

fluid of

centration of lymph flowing from these tissues is near

formed in the intestines has a protein concentration as

lymph normally is derived from the liver and intes-

for absorption of nutrients from the gastrointestinal

as 1 to 2 per cent fat.

push their way between the endothelial cells of the
lymphatic capillaries and in this way enter the lymph.

particles are almost entirely removed and destroyed,
as discussed in Chapter 33.

About 100 milliliters per hour of lymph flows through
the thoracic duct
mately another 20 milliliters flows into the circulation

mated lymph flow of about 120 ml/hr or 2 to 3 liters

16–10 shows the effect of different levels of interstitial
fluid pressure on lymph fl
Note that normal lymph flow is very little at intersti-
tial fluid pressures more negative than the normal

value of

Hg (atmospheric pressure), flow increases more than

fluid pressure also increases lymph flow if the lymph

the following:
∑ Elevated capillary pressure
∑ Decreased plasma colloid osmotic pressure
∑ Increased interstitial fluid colloid osmotic pressure
∑ Increased permeability of the capillaries
All of these cause a balance of fluid exchange at the
blood capillary membrane to favor fluid movement

fluid

flow all

–10 that when the inter-

stitial fluid pressure becomes 1 or 2 millimeters greater

lymph flow fails to rise any further at still higher pres-

tissue pressure not only increases entry of fluid into
the lymphatic capillaries but also compresses the

ing lymph fl

lymph flow reaches what is called the “maximum
lymph fl

”

–10.

Endothelial cells

Anchoring filaments

Valves

Special structure of the lymphatic capillaries that permits passage

FIGURE 16–9

of substances of high molecular weight into the lymph.

Relative lymph flow

–2

–4

–6

(mm Hg)

2 times/

mm Hg

7 times/

mm Hg

(0 mm Hg). (Courtesy Drs. Harry Gibson and Aubrey Taylor.)

, rises slightly above atmospheric pressure

interstitial pressure, P

leg of a dog. Note that lymph flow reaches a maximum when the

Relation between interstitial fluid pressure and lymph flow in the

FIGURE 16–10

First, remember that small amounts of proteins

uid pressure.

uid, and (3) the interstitial

uids, (2) the volume of

tissue spaces. Therefore, the lymphatic system also

Volume, and Interstitial Fluid Pressure

Concentration, Interstitial Fluid

Role of the Lymphatic System in

of lymph flow is determined by the product of intersti-

pump. Therefore, one can state that, roughly,

above discussion, one can see that the two primary

From the

Summary of Factors That Determine Lymph Flow.

lymphatics.

vessels also contract rhythmically. Therefore, it is

some animal tissues (e.g., the bat

laments. In

The lymphatic capillary endothelial cells also

the cell junctions.

Therefore, the pressure pushes the lymph forward into

ping edges of the endothelial cells to close like valves.

Then, when the tissue is compressed, the pressure

through the junctions between the endothelial cells.

laments pull on the wall of the lymphatic capillary,

the tissue and causes the tissue to swell, the anchoring

laments. Therefore, each time excess

As explained earlier in the chapter, the walls of the

the lymph pumping by the larger lymph vessels.

lary is also capable of pumping lymph, in addition to

The terminal lymphatic capil-

Lymphatic Capillary Pump.

almost zero.

versely, during periods of rest, lymph

ow 10- to 30-fold. Con-

cise, often increasing lymph

The lymphatic pump becomes very active during exer-

In order of their importance, such factors are:

compresses the lymph vessel also can cause pumping.

vessel walls, any external factor that intermittently

of the Lymphatics.

100 mm Hg.

large lymph vessel such as the thoracic duct, this lym-

nally emptied into the blood circulation. In a very

and a few seconds later it, too, contracts, the process

lymphatic segment. This

lling of a segment causes it to contract, and the

functions as a separate automatic pump. That is, even

the vessel automatically contracts. Furthermore, each

uid, the smooth muscle in the wall of

in animals and in human beings, show that when a

Motion pictures of exposed lymph vessels, both

phatic capillaries empty.

The Microcirculation and the Lymphatic System

Chapter 16

193

16–11 in collecting lymphatics into which the lym-

collecting lymphatic or larger lymph vessel becomes
stretched with fl

segment of the lymph vessel between successive valves

slight fi
fluid is pumped through the next valve into the next

fills the subsequent segment,

continuing all along the lymph vessel until the fluid is
fi

phatic pump can generate pressures as great as 50 to

Pumping Caused by External Intermittent Compression

In addition to the pumping caused

by intrinsic intermittent contraction of the lymph

∑ Contraction of surrounding skeletal muscles
∑ Movement of the parts of the body
∑ Pulsations of arteries adjacent to the lymphatics
∑ Compression of the tissues by objects outside the

body

flow is sluggish,

lymphatic capillaries are tightly adherent to the sur-
rounding tissue cells by means of their anchoring
fi

fluid enters

fi
and fluid flows into the terminal lymphatic capillary

inside the capillary increases and causes the overlap-

the collecting lymphatic instead of backward through

contain a few contractile actomyosin fi

’s wing) these fila-

ments have been observed to cause rhythmical con-
traction of the lymphatic capillaries in the same way
that many of the small blood and larger lymphatic

probable that at least part of lymph pumping results
from lymph capillary endothelial cell contraction
in addition to contraction of the larger muscular

factors that determine lymph flow are (1) the intersti-
tial fluid pressure and (2) the activity of the lymphatic

the rate

tial fluid pressure times the activity of the lymphatic
pump.

Controlling Interstitial Fluid Protein

It is already clear that the lymphatic system functions
as an “overflow mechanism” to return to the circula-
tion excess proteins and excess fluid volume from the

plays a central role in controlling (1) the concentration
of proteins in the interstitial fl
interstitial fl

Let us explain how these factors interact.

leak continuously out of the blood capillaries into the

Pores

Lymphatic

capillaries

Collecting

lymphatic

Valves

Structure of lymphatic capillaries

FIGURE 16–11

and a collecting lymphatic,
showing also the lymphatic
valves.

American Physiological Society, 1984, p 467.

(eds): Handbook of Physiology. Sec. 2, Vol. IV. Bethesda:

across the microcirculation. In: Renkin EM, Michel CC

Taylor AE, Granger DN: Exchange of macromolecules

Res 39:375, 2002.

Transendothelial transport: the vesicle controversy. J Vasc

Rippe B, Rosengren BI, Carlsson O, Venturoli D:

Immunol 4:35, 2004.

Oliver G: Lymphatic vasculature development. Nat Rev

Immunol 4:360, 2004.

endothelial venules: dogmas and enigmas. Nat Rev

Miyasaka M, Tanaka T: Lymphocyte traf

Rev 79:703, 1999.

Michel CC, Curry FE: Microvascular permeability. Physiol

phia: WB Saunders Co, 1975.

II. Dynamics and Control of the Body Fluids. Philadel-

Guyton AC, Taylor AE, Granger HJ: Circulatory Physiology

Circ Res 19:412, 1966.

uid mobility.

sure: III. Its effect on resistance to tissue

Guyton AC, Scheel K, Murphree D: Interstitial

capillary wall. Circ Res 19:1022, 1966.

pressure: IV. Its effect on

Guyton AC, Prather J, Scheel K, McGehee J: Interstitial

sure. Physiol Rev 51:527, 1971.

Guyton AC, Granger HJ, Taylor AE: Interstitial

curves of interstitial space. Circ Res 16:452, 1965.

uid pressure: II. Pressure-volume

Guyton AC: Interstitial

12:399, 1963.

on pressures in implanted perforated capsules. Circ Res

Guyton AC: Concept of negative interstitial pressure based

function: current perspectives. Ann N Y Acad Sci 979:178,

Gashev AA: Physiologic aspects of lymphatic contractile

Thromb Vasc Biol 23:1161, 2003.

caveolae, and endothelial cell function. Arterioscler

Frank PG, Woodman SE, Park DS, Lisanti MP: Caveolin,

Nat Rev Mol Cell Biol 5:261, 2004.

Dejana E: Endothelial cell-cell junctions: happy together.

Kidney Int 63:809, 2003.

Amico G, Bazzi C: Pathophysiology of proteinuria.

uid volume. Physiol Rev 73:1,

Aukland K, Reed RK: Interstitial-lymphatic mechanisms in

occurs, which is discussed

pressure,

partial vacuum. When the tissues lose their negative

uid pressure, which is actually a

at these places, the tissues are held together by the

over the back of the hand or over the face. Yet even

tissues slide over one another, such as the skin sliding

even absent. This occurs particularly at points where

the body, connective tissue

bers. However, at many places in

Traditionally, it has been assumed that the different

Body Tissues Together

Pressure as a Means for Holding the

uid from the blood capillaries.

state; they will remain balanced at these steady state

interstitium from the blood capillaries. Therefore, the

uid pressure, the return of protein and

Thus, once the interstitial

mulated in the spaces.

previously. This in turn carries away the excess inter-

ow, as explained

Third, the increasing interstitial

uid pressure.

lary wall by the proteins and into the interstitium, thus

into the interstitium. Therefore, in effect,

Second, the increasing colloid osmotic pressure in

uids.

uid, and this in

ends of the blood capillaries. Therefore, these proteins

interstitium. Only minute amounts, if any, of the leaked

194

Unit IV

The Circulation

proteins return to the circulation by way of the venous

tend to accumulate in the interstitial fl
turn increases the colloid osmotic pressure of the
interstitial fl

the interstitial fluid shifts the balance of forces at the
blood capillary membranes in favor of fluid filtration

fluid is

translocated osmotically outward through the capil-

increasing both interstitial fluid volume and interstitial
fl

fluid pressure

greatly increases the rate of lymph fl

stitial fluid volume and excess protein that has accu-

fluid protein concentra-

tion reaches a certain level and causes a comparable
increase in interstitial fluid volume and interstitial
fl

fluid by way

of the lymphatic system becomes great enough to
balance exactly the rate of leakage of these into the

quantitative values of all these factors reach a steady

levels until something changes the rate of leakage of
proteins and fl

Significance of Negative Interstitial Fluid

tissues of the body are held together entirely by
connective tissue fi

fibers are very weak or

negative interstitial fl

fluid accumulates in the spaces and the

condition known as edema
in Chapter 25.

References

the control of extracellular fl
1993.

D’

2002.

fluid pres-

fluid

fluid movement through the

fluid pres-

ficking across high