S. Faubel and J.

Topf 3 Starling’s Law

3 Starling’s Law

49
The Fluid, Electrolyte and Acid-Base Companion

Introduction
Three factors affect the movement of water be-

tween body water compartments.
Weight
of
water 1
Hydrostatic pressure

so lu 2
Osmotic pressure
te

3Membrane characteristics
The previous chapter took a brief look at the factors which influence the
distribution of water between compartments. These factors are hydrostatic
pressure, osmotic pressure and membrane characteristics.
Hydrostatic pressure is a force generated by water. Hydrostatic pres-
sure pushes water out of a compartment.
Osmotic pressure is a force exerted by solutes. Osmotic pressure draws
water into a compartment. This force is dependent only on the concentra-
tion of particles (osmolality) in solution.
Membrane characteristics affect the ability of water and solute to move
between compartments.
This chapter focuses on how these factors are incorporated into Starling’s
law. Starling’s law governs fluid shifts between compartments and can be
used to understand all fluid accumulations, including peripheral edema,
pleural effusions and ascites.

There are two forces governing the movement of water between Aaa
compartments: __________ pressure and osmotic pressure. hydrostatic

Osmotic ___________ is the ability of a solute to cause the move- pressure

ment of _______. water
50
S. Faubel and J. Topf 3 Starling’s Law

Starling’s law
Net hydrostatic pressure and net osmotic pressure

determine the movement of water between compartments.
capillary interstitium capillary interstitium

(capillaryhp– interstitial hp ) (capillaryop– interstitial op )

net hydrostatic pressure net osmotic pressure

To determine where water will flow between the plasma and interstitial
compartments, it is necessary to look at the net hydrostatic pressure and
net osmotic pressure of each compartment.
Net hydrostatic pressure is the difference between the hydrostatic pres-
sure in the capillary and the hydrostatic pressure in the interstitium. Wa-
ter flows out of the compartment with the greater hydrostatic pressure. In
the diagram above, the capillary hydrostatic pressure is greater than the
interstitial hydrostatic pressure; the net hydrostatic pressure causes move-
ment of water out of the capillary.
Net osmotic pressure is the difference between the osmotic pressures
in the capillary and interstitium. Water flows into the compartment with
the higher osmotic pressure. In the diagram above, the capillary osmotic
pressure is higher; the net osmotic pressure causes the movement of water
into the capillary.

___________ pressure pushes water out of a compartment. Hydrostatic

___________ pressure draws water into a compartment. Osmotic

______ hydrostatic pressure is the capillary hydrostatic pressure Net

minus the interstitial hydrostatic pressure.

Net osmotic pressure is the ________ osmotic pressure minus the capillary
interstitial osmotic pressure.

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The Fluid, Electrolyte and Acid-Base Companion

Starling’s law
The membrane factors Lp, S and s can effect the

movement of water between compartments.

MEMBRANE CHARACTERISTICS

Lp and S
porosity and surface area
modulate hydrostatic pressure

s
permeability to a solute mod-
ulates osmotic pressure

There are three independent membrane characteristics which affect the

movement of water between compartments. Two of them modulate hydro-
static pressure and one modulates osmotic pressure.
Hydrostatic pressure is affected by membrane surface area and the abil-
ity of water to pass through the membrane. The surface area is represented
by an uppercase S and the porosity is represented by Lp. The membrane
factors affecting hydrostatic pressure are rarely clinically significant.
Osmotic pressure is modified by the permeability of the membrane to a
solute. If the membrane is perfectly permeable to a solute, then the solute
diffuses across the membrane (instead of osmotically drawing in water).
Permeability of a membrane to a solute is represented by a lowercase s and
ranges from zero, completely permeable, to one, completely impermeable.
Membrane permeability is clinically relevant in disorders which disrupt
membrane integrity (e.g., sepsis).

The membrane factors which modulate hydrostatic and osmotic aaa

forces are: ___, S and s. Lp

Two membrane characteristics modulate hydrostatic pressure: Lp

and ____. S

The membrane factor s represents the ___________ of the mem- permeability

brane to solutes, a clinically important factor.

52
S. Faubel and J. Topf 3 Starling’s Law

Starling’s law
Starling’s law is the mathematical representation

of the movement of water between compartments.
NET FILTRATION PRESSURE

Lp × S (capillaryhp– interstitial hp ) s (capillaryop– interstitial op)

net hydrostatic pressure net osmotic pressure

Positive net filtration pressure Negative net filtration pressure

If net filtration pressure is positive, water If net filtration pressure is negative, water
moves from the capillary into the interstitium. moves from the interstitium into the capillary.

Starling’s law is the mathematical representation of the principles of hy-

drostatic pressure, osmotic pressure and membrane characteristics applied
to the movement of water between the capillaries and the interstitial space.
The formula is arranged so that if net filtration pressure is positive (net
hydrostatic pressure greater than net osmotic pressure), water moves from
the capillaries into the interstitium. If net filtration pressure is negative
(net osmotic pressure greater than net hydrostatic pressure), then water
moves from the interstitium to the capillaries.
The following pages review the clinical consequences of alterations in the
variables of Starling’s Law which cause the movement of water out of the
capillaries.

The movement of ______ between capillaries and the interstitium water

is ____________ represented by Starling’s law. mathematically

The equation for Starling’s law contains _______ forces: hydro- two
static pressure and _______ pressure. osmotic

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The Fluid, Electrolyte and Acid-Base Companion

Net osmotic pressure and net hydrostatic pressure change

from one end of the capillary bed to the other.

lymphatic drainage
ARTERIAL END

VENOUS END
At the proximal end of the capillary, the At the distal end of the capillary, the net
net filtration pressure is positive and wa- filtration pressure is negative and water
ter moves out of the capillary. moves into the capillary.

The application of Starling’s law to the flow of fluid in and out of the
capillary is a dynamic process. At the arterial end of the capillary, the
net filtration pressure is positive, which causes the movement of water
from the capillary into the interstitium. This movement of fluid out of
the capillary concentrates plasma protein and dilutes interstitial pro-
tein. As fluid moves through the capillary, hydrostatic pressure falls
due to friction against the capillary walls. The sum of these changes
causes the venous end of the capillary to have a negative net filtration
pressure and resorb fluid from the interstitium.
This push-and-pull pattern in the capillary bed is useful because it
allows the capillary to deliver oxygen and nutrients (at the arterial end)
and pick up carbon dioxide and other waste (at the venous end).
The average net filtration pressure across the entire capillary is posi-
tive: the net outward movement of water is greater than the net inward
movement of water. The excess water which is filtered but not resorbed
does not accumulate in the interstitial space. The lymphatic system
absorbs this excess fluid and returns it to the circulation via the tho-
racic duct.

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S. Faubel and J. Topf 3 Starling’s Law

Water movement out of the capillary
Increased net filtration

can be due to increased net hydrostatic pressure.

ARTERIAL END OF CAPILLARY VENOUS END OF CAPILLARY

pre-capillary sphincter

increased increased
arterial venous
pressure normal pressure elevated pressure pressure

no change in net
increased net filtration pressure
filtration pressure

Increased capillary hydrostatic pressure increases net filtration pressure

resulting in the movement of fluid from capillaries into the interstitium.
It is an increase in venous hydrostatic pressure which results in a change
in net filtration pressure. The arterial ends of capillaries contain pressure-
sensitive precapillary sphincters which compensate for changes in blood
pressure. Therefore, the increased arterial blood pressure of hypertension
does not affect hydrostatic pressure and does not cause edema.
Clinically, increased hydrostatic pressure is seen in congestive heart fail-
ure and cirrhosis. The consequences of increased hydrostatic pressure in-
clude peripheral edema, pulmonary edema and ascites.

Increased venous hydrostatic pressure is the cause of the vast majority of cases of periph-
eral edema. Peripheral edema is discussed further in ChapterVolume
4, Regulation .

The clinical consequences of increased hydrostatic pressure include aaa

peripheral ________, pulmonary _______ and ascites. edema; edema

Increased _________ blood pressure does not cause an increase in arterial

capillary hydrostatic pressure.

Increased venous hydrostatic pressure _________ net filtration pressure. increases

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The Fluid, Electrolyte and Acid-Base Companion

Clinical correlation: Increased venous hydrostatic pressure

from congestive heart failure causes pulmonary edema.

heart failure pulmonary edema

Congestive heart failure (CHF) is characterized by the inability of

the heart to maintain adequate tissue perfusion. With severe CHF, the
forward flow of blood from the heart is so poor that blood accumulates
in the pulmonary venous circulation which increases the hydrostatic
pressure in the pulmonary capillaries. Elevated hydrostatic pressure
in the pulmonary capillaries increases the movement of fluid from the
capillaries into the alveoli. The accumulation of fluid in the alveoli is
pulmonary edema.
Clinically, pulmonary edema is characterized by shortness of breath
and crackles in the lung bases by auscultation. Other signs of heart
failure include increased jugular venous distension, peripheral edema
and an S3 gallop.
Acute pulmonary edema can be treated with furosemide and mor-
phine, both of which decrease venous hydrostatic pressure (pre-load).
Furosemide decreases hydrostatic pressure by increasing urine output
which decreases the amount of fluid in circulation; it also is thought to
dilate the pulmonary veins and directly reduce hydrostatic pressure.
Morphine dilates venous vessels and has the additional effect of calm-
ing an anxious patient.

56
S. Faubel and J. Topf 3 Starling’s Law

Water movement out of the capillary
Increased net filtration

pressure can be due to decreased net osmotic pressure.

DECREASED PRODUCTION OF PLASMA PROTEIN INCREASED LOSS OF PLASMA PROTEIN

cirrhosis severe nephrotic protein-losing

malnutrition syndrome enteropathies

Since proteins are the primary factor influencing osmotic pressure between
the plasma and interstitium, changes in plasma protein concentration can af-
fect net filtration pressure. A decrease in the plasma protein concentration rela-
tive to the interstitial compartment increases net filtration pressure and causes
the movement of water out of the capillaries and into the interstitium.
Changes in net osmotic pressure do not become clinically significant until
the plasma albumin concentration is less than 2 g/dL (normal 3.5 to 5.5 g/dL).
Decreased plasma protein concentration can be due to decreased production
(e.g., chronic liver disease, severe malnutrition) or increased loss (e.g., neph-
rotic syndrome, protein losing enteropathies).

Albumin represents the majority of plasma proteins.

As reviewed in Chapter 2,Water, Where
Are You, the capillary membrane is permeable to electrolytes and nonelectrolytes, but not to
protein. For a solute to exert osmotic pressure (draw water in), the membrane has to be
impermeable to it.This explains why plasma protein is the primary solute which influences
osmotic pressure.

Decreased plasma protein can _________ net filtration pressure. increase

Increased net filtration pressure from low plasma albumin does not oc- albumin
cur until the plasma albumin falls below _______ g/dL. 2

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The Fluid, Electrolyte and Acid-Base Companion

Water movement out of the capillary
Increased net filtration

can be due to increased membrane permeability.

water water
protein protein

The final factor of Starling’s law which affects the movement of fluid out
of capillaries is membrane permeability.
Factors which increase membrane permeability are those which damage
the membrane. Capillary membrane damage may be caused by infection,
inflammation, sepsis, trauma, malignancy and adult respiratory distress
syndrome (ARDS). Direct membrane damage causes the extravasation of
both water and proteins.
With membrane damage, s rises and more water can exit without a rise
in hydrostatic pressure.

Capillary ___________ increases membrane permeability. damage

Capillary damage increases the loss of water and _________ from proteins
the capillary.

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S. Faubel and J. Topf 3 Starling’s Law

Clinical correlation: Fluid collections are always due to a

change in one of the components of Starling's law.

ascites peripheral edema pleural effusion pulmonary edema

All fluid accumulations in the body are due to a change in one of the
components of Starling's law: hydrostatic pressure, osmotic pressure or
capillary permeability. This rule is the basis for the laboratory analysis
of a fluid accumulation. Determining the amount of protein and other
factors contained in the fluid can help determine if the fluid collection
is due to a change in hydrostatic pressure, osmotic pressure or capillary
permeability.
In general, a fluid collection with a low protein content is due to a
change in hydrostatic pressure and is called a transudate. Transuda-
tive effusions are associated with disorders characterized by increased
venous hydrostatic pressure such as congestive heart failure and cir-
rhosis. A change in osmotic pressure also results in a transudative fluid
collection.
A fluid collection with a high protein content is due to capillary dam-
age and is called an exudate. Exudative effusions are caused by disor-
ders which directly damage capillary membranes, such as inflamma-
tion, infection and malignancy.
Although the fluid from peripheral edema cannot be analyzed, think-
ing about the differential diagnosis in terms of which aspect of Starling’s
law has been altered is useful. A “transudative peripheral edema” is
associated with CHF and cirrhosis while an “exudative peripheral
edema” is associated with infection (local or systemic), trauma and ma-
lignancy.

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The Fluid, Electrolyte and Acid-Base Companion

Clinical correlation: Pleural effusions are categorized as ei-

ther transudates or exudates.

Transudate Exudate
congestive heart failure pneumonia
cirrhosis with ascites other infections
nephrotic syndrome malignancy
peritoneal dialysis collagen vascular
superior vena cava diseases (rheumatoid
obstruction arthritis, lupus)
myxedema sarcoidosis
pulmonary embolism drugs
Meigs’ syndrome uremia
pleural effusion

A pleural effusion is an accumulation of fluid between the parietal

and visceral pleura of the lungs*. The parietal pleura lines the thoracic
cavity and is connected to the visceral pleura which lines the surface of
the lungs. The space between the visceral and parietal pleura normally
contains only a small amount of fluid.
Pleural effusions can accumulate due to a wide variety of insults which
interfere with the absorptive capacity of the capillaries and lymphatics
of the visceral pleura. Although the differential diagnosis of a pleural
effusion is extensive, the first step in identifying the cause of a pleural
effusion is determining if it is a transudate or an exudate. For a pleural
effusion to be an exudate, one of the following characteristics must be
present (if none are present, the fluid is a transudate):
• pleural fluid protein/plasma protein greater than 0.5
• pleural fluid LDH/plasma LDH greater than 0.6
• pleural fluid LDH > two-thirds upper limit of normal plasma LDH
Conditions resulting in an exudative pleural effusion include those
which damage the capillary wall and increase membrane permeability.
With capillary damage, substances such as protein and LDH, which are
normally confined to the vascular space, are able to enter the pleural
space. The most common causes of an exudative pleural effusion are
infection and malignancy.
Conditions resulting in a transudative pleural effusion are caused by
conditions which alter hydrostatic and/or osmotic pressure. The most
common causes of transudative pleural effusions are due to increased
hydrostatic pressure from congestive heart failure and cirrhosis.
*Don't confuse pleural effusion with pulmonary edema; pulmonary edema is the accumu-
lation of fluid in the alveoli of the lungs.

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S. Faubel and J. Topf 3 Starling’s Law

Clinical correlation: Ascites is categorized by the albumin

gradient.
albumin plasma ascitic
gradient albumin (mg/dL) albumin (mg/dL)

High gradient ( > 1.1 g/dL) Low gradient ( < 1.1 g/dL)
cirrhosis malignancy
hepatitis tuberculosis
congestive heart failure pancreatic disease
portal vein thrombosis nephrotic syndrome
myxedema

Ascites is the accumulation of fluid within the peritoneal cavity. The

most common etiology of ascites is extensive liver disease. Extensive
liver disease increases the hydrostatic pressure of the portal system
which results in an ascitic fluid with a low protein concentration.
Instead of referring to ascitic fluid as either a transudate or exudate,
the terms high albumin gradient and low albumin gradient are used.
The albumin gradient is the difference between the plasma and ascitic
albumin concentrations. A high albumin gradient is greater than 1.1 g/
dL and a low albumin gradient is less than 1.1 g/dL.
Ascitic fluid with a high albumin gradient is equivalent to a transu-
date; it is due to increased hydrostatic pressure from portal hyperten-
sion. A high albumin gradient means that the difference between the
plasma albumin and the ascitic albumin is large and that little albu-
min was able to pass from the capillaries into the ascitic fluid.
Ascitic fluid with a low albumin gradient is equivalent to an exu-
date; it is due to factors other than portal hypertension, such as alter-
ations in membrane permeability from malignancy or infection. The
low albumin gradient indicates that there is little difference between
the plasma and ascitic albumin concentration and that a large amount
of plasma albumin was able to cross through damaged capillaries and
enter the ascitic fluid.

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The Fluid, Electrolyte and Acid-Base Companion

Summary
Starling’s law.
The movement of water out of capillaries is governed by three factors:

hydrostatic pressure osmotic pressure membrane

characteristics

These factors are mathematically represented by Starling’s law.

NET FILTRATION PRESSURE

Lp × S (capillaryhp– interstitial hp ) s (capillaryop– interstitial op )

net hydrostatic pressure net osmotic pressure

Factors which increase net filtration pressure increase the movement of

fluid out of the capillary. Increased net filtration pressure can be caused by
increased hydrostatic pressure, decreased osmotic pressure and increased
capillary permeability.
The clinical applications of Starling’s law are vast. All fluid accumula-
tions are due to an alteration in one of the factors of Starling’s law.

ascites peripheral edema pleural effusion pulmonary edema

Fluid collections with a low protein content are transudates and are due
to an increase in hydrostatic pressure while fluid collections with a high
protein content are exudates and are due to an increase in membrane per-
meability. Because it so effectively narrows the differential diagnosis, analysis
of pleural and ascitic fluid is commonly performed to establish whether the
fluid is a transudate or exudate.
PLEURAL FLUID ANALYSIS * ALBUMIN GRADIENT = PLASMA ALBUMIN – ASCITES ALBUMIN
• pleural fluid protein more HIGH GRADIENT ( > 1.1 g/dL) LOW GRADIENT ( < 1.1 g/dL)
than 50% of serum protein • cirrhosis • malignancy
• pleural fluid LDH more than • hepatitis • tuberculosis
60% of serum LDH • congestive heart failure • pancreatic disease
• pleural fluid LDH more than • portal vein thrombosis • nephrotic syndrome
66% of the upper limit of • myxedema
normal for serum LDH

* one of the three is required for

the fluid to be an exudate

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