CHAPTER 6

Pulmonary Blood Flow

CHAPTER OUTLINE . M h . m of Hypoxic Pulmonary Vasoconstriction

1. ec anIs . .
I. Pulmonary Vasculature f Hypoxic Pulmonary Vasoconstnct1on
.
2 L O . D.
II. Bronchial Vasculature 3 . Inhaled vasodilators in Acute Respiratory ,stress
Ill. Pulmonary and Systemic Pressures Syndrome
A. Clinical Measurement of Pulmonary Blood Pressures VI. Distribution of Pulmonary Blood Flow
and Flows A. Gravitational and Pressure Effects: Zones of Blood
1. Measurement of Pulmonary Blood Pressures
Flow
2. Measurement of Pulmonary Blood Flow or Cardiac
1. Zone I Blood Flow
Output 2. Zone II Blood Flow
IV. Pulmonary Vascular Resistance 3 . Zone Ill Blood Flow
A. Calculation of Pulmonary Vascular Resistance 4. Factors Affecting Zones of Blood Flow
B. Distribution of Pulmonary Vascular Resistance
B. Normal Matching of Ventilation and Blood Flow
V. Factors Affecting Pulmonary Vascular Resistance
1. Dead Space and Shunt Effects in the Normal Lung
A. Passive Factors VII. Liquid Movement Across the Alveolar Capillary
1. Lung Volume: Effects on Alveolar and Extraalveolar
Membrane
Vessels
2. Vascular Pressure: Recruitment and Distention A. Capillary Fluid Dynamics
B. Pulmonary Edema
3. Blood Volume
1. Increased Hydrostatic Pressure
B. Active Factors
1. Neurogenic Stimuli 2. Increased Capillary Permeability
2. Humoral Agents and Nitric Oxide 3. Decreased Plasma Oncotic Pressure
3. Chemical Factors 4. Lymphatic Insufficiency
C. Physiological Function of Hypoxic Pulmonary VIII. Points to Remember
Vasoconstriction

OBJECTIVES
After reading this chapter, you will be able to: • Explain how hypoxic
both benef· · d h pu 1monary vasoconstriction can be
• Describe how the pulmonary and systemic circulations dif- Icia 1 an armful
fer anatomically and functionally • Explain why the h .
response is diminishei~~xic ~ulmonary va~oconstriction
• Explain how blood flow, pressure, and vascular resistance in
• Explain why inhaled ~ertain pulmonary diseases
the pulmonary circulation can be assessed through pulmo- . vasod,lators can bring about beneficial
nary artery catheterization h
P ysI0 1ogical changes that .
• Distinguish among causes of high pulmonary artery pres- temic administration ro t are not possible through sys-
• E 1. u es
sure through data obtained from the pulmonary artery xp a,n why gravity create h . .
catheter blood flow zones in the s t ree distinct physiological
I nd
• Explain how right and left ventricular pumping function can cally from one another ung, a how they differ physiologi-
be assessed through pulmonary artery catheterization • Describe how mechanical and . .
• Calculate pulmonary vascular resistance convert a blood flow zo . physiological changes can
zone ne in the lun g t o a different
. type of
• Differentiate between passive and active factors that affect
pulmonary vascular resistance • Explain why the match b
i . etween blood fl
• Explain how the pulmonary vasculature can accommodate n an upright individual is differ . ow and ventilation
great increases in blood flow during exercise without signifi- the lung apex ent in the lung base than in
cantly increasing blood pressure • Describe the kinds of circulatory
. b
• Explain why hypoxemia affects the right ventricle differently monary edema a normalities cause pul-
than the left ventricle

110

b=tiii;JMl#M
acidemia
alkalemia
central venous pressure (CVP)
cyclic guanosine monophosphate (cGMP)
endothelium-derived relaxing factor (EDRF)
endotoxins
extraalveolar vessels
hydrostatic
hypervolemia
hypoxia
hypoxic pulmonary vasoconstriction (HPV)
oncotic pressure
osmotic
I PULMONARY VASCULATURE
he vascular system of the body consists of separate pul-
T monary and systemic circulations operating in series
(Figure 6-1). Each circulation receives its blood from
the other; each has its own reservoir, pump, and set of vessels.
The right ventricle receives mixed venous blood through the
tricuspid valve from its reservoir, the right atrium, and pumps
it through the pulmonic valve, which marks the beginning
of the pulmonary circulation. 1 This relatively deoxygenated
blood flows through pulmonary arteries and arterioles to an
immense alveolar capillary bed where it is reoxygenated. The
capillary bed consists of extremely short, interconnected seg-
ments spreading 75 to 100 mL of blood over a 70-m 2 area, or
about half the size of a tennis court. 1 Comroe 2 described the
capillary bed as two sheets of endothelium held apart in places
by posts, similar to an underground parking garage. Rather
than flowing through numerous individual tubes _(as in sys-
temic capillaries), pulmonary blood flows more like a she~t
over the alveoli, maximizing its exposure to alveolar gases. This
structural arrangement shortens the distance for oxygen and
carbon dioxide diffusion between air and blood to one tenth of
the diffusion distance that exists between systemic capillaries
and tissue cells. 1
After leaving the alveoli, the capillaries converge to form
venules and veins. The newly oxygenated blood flows through
four major pulmonary veins (two from each lung) into the l~ft
atrium, the reservoir for the left ventricle. The pulmonary vem
orifices in the left atrial wall mark the end of the pulmonary
circulation. I Blood continues to flow out of the left atrium
through the mitral valve into the left ventricle, which pum~s
the blood through the aortic valve int? t?e ao~a. The aortic
valve marks the beginning of the systemic circulat10n. The aorta
distributes the oxygenated blood thr?ugh its many branches to
systemic arteries, arterioles, and capillary beds thr~ughout the
body, supplymg · oxygen to tissue cells and. removmg the car- .
hon dioxide they produce. Beyond the capillary beds, systemic
venules and veins converge to return the oxygen-poor blood to
. th vena cavae which mark the end of the
the n'ght atnum
.
VIa e ' about 1% to 2% greater than right ventricular output. 3
systemic circulation.
CHAPTER 6 Pulmonary Blood Flow 111
C? p
persistent pulmonary hypertension of the newborn (PPHN)
preload
proteinuria
pulmonary artery pressure (PAP)
pulmonary capillary wedge pressure (PCWP)
pulmonary edema
pulmonary vascular resistance (PVR)
right atrial pressure (RAP)
septicemia
shunt
systemic vascular resistance (SVR)
Valsalva maneuver
ventilation-perfusion ratio (V/0)
The total cardiac output (Q1 ) is simultaneously pumped
through both circulations each minute. Right and left ven-
tricular outputs must be essentially equal over time; otherwise,
blood would accumulate in one of the circulations. Small differ-
ences in outputs may occur briefly for a few heartbeats, but over
time, individual ventricular outputs are equal in healthy hearts.
Figure 6-1 illustrates pulmonary and systemic circulations with
their associated pressures.
The pulmonary arteries and arterioles have much thinner
walls and less smooth muscle than systemic arteries and arteri-
oles. Therefore, pulmonary arterioles cannot constrict as effec-
tively as systemic arterioles. Pulmonary veins and venules also
have sparse smooth muscle, differing little in structure from
pulmonary arteries and arterioles. Pulmonary arteries generally
follow a course parallel with bronchi, whereas pulmonary veins
leave the lung through different routes. Without this anatomi-
cal difference, distinguishing pulmonary arteries from veins on
a chest x-ray image would be difficult because of their structural
similarities. 2
Pulmonary capillaries also differ significantly from systemic
capillaries; as noted previously, pulmonary capillary blood
flows in thin sheets, as opposed to the distinctly tubular flow
in systemic capillaries. The thin walls of pulmonary vessels and
vast area of the capillary bed make the pulmonary vasculature
highly distensible compared with the systemic vasculature.
I BRONCHIAL VASCULATURE · }(.
The supporting tissues of the tracheobronchial tree, including
airways down through the terminal bronchioles, are supplied
with oxygenated blood through the systemic bronchial arter-
ies. (See the section on blood supply to the lungs in Chapter I.)
Bronchial systemic venous blood dra~ns directly into the pul-
monary veins, mixing oxygen-poor blood with freshly oxygen- I
ated pulmonary venous blood on its way to the left ventricle. 3 I
r
Bronchial blood flow is only 1% to 2% of the cardiac output,
which means that the anatomical shunt from this source is usu-
11
ally less than 2%; this also means that left ventricular output is
I
I\ 112 SECTION I The Respiratory System

Circulation to
tissues of head
and upper body

Lung

'I
•
I ·l
,, ,WN:1
9mm Hg

Circulation to
tissues of
10 mm Hg lower body

20 mm Hg Systemic circulation

figure 6-1 Comparison of pulmonary and systemic blood flows and pressures. (Adapted from Thibodeau GA, Patton KT: Anatomy & physiology,
ed 5, St Louis, 2003, Mosby.)

--- - - -
CONCEPT QUESTION 6-1 the rest is distributed equally between pulmonary arterial and
venous vessels. 3 The capillary blood volume of 70 mL is about
Explain the way anatomical shunt through the bronchial circu- equal to the volume ejected by the right ventricle with each
lation causes an oxygen pressure (PO2) difference between contraction (the right ventricular stroke volume). Pulmonary
alveolar gas and arterial blood. capillary blood is thus almost completely replaced with each
heartbeat, which means a red blood cell travels through the
capillaries in about 0.75 second. Pulmonary blood flow almost
PULMONARY AND SYSTEMIC stops between each ventricular beat, which explains its pulsatile
nature. 1,3
PRESSURES
The highly expandable pulmonary vascular bed serves as a
Figure 6-1 shows that the pulmonary ci~culation is a_lo~- backup reservoir that shields the left atrium from sudden changes
pressure, low-resistance system compared with the system'. c c1~- !n right ventricular output. If venous return to the right ventricle
culation. The lower resistance in the pulmonary circulatwn 1s mcre~ses sudden!'., as wo~ld occur during sudden strenuous
man11es·c t ed by the fact that its pressures are lower .even . tho ugh
. exercise, left ventricular filling pressure increases gradually over
· receives
1t · the same cardiac outp ut as the systemic circulatwn . two or three cardiac cycles rather than increasing abruptly.
·
rece1ves. The resistance to blood flow in th e pulmonary . • ulcucula-
· 1
· · b ou tone tenth as great as it is in the
t10n1sa . systemIC
. . circ. ation.
Bl00 d fl 0 w through the pulmonary circulatw n 1s highly pul- Clinical Measurement of Pulmonary Blood
Pressures and Flows
.
sa tile ra th er th an continuous as in systemic .capillaries.
. The total
· the pulmonary circu lat10n 1 s about 450 mL,
volume o fbl oo d m b Measurement of Pulmonary Blood Pressures
. . nl
wh1Ch 1s o y 9 o o '¾ f the total circulati ng blood volume.
. A out ~yste'.11ic blood pressure is easily measured by simple non-
70 mL of this blood is in the capillaries at any given moment; mvas1ve means. However, measurement of pressures in the
 CHAPTER 6 Pulmonary Blood Flow 113

Ballooa ;mlj'o" wlw

in~~~~~n---- Thermistor clonnector

port
Proximal

Extra
injection - - -
port

Distal lumen-------"

I
Balloon

Figure 6-2 Typical quadruple channel pulmonary artery catheter. After insertion, the distal lumen rests in the pulmonary artery, and the proximal
lumen rests in the right atrium. Both communicate with their respective injection ports. (From Wilkins RL, Stoller JK, Kacmarek RM: Egan's
fundamentals of respiratory care, ed 9, St Louis, 2009, Mosby.)

pulmonary circulation requires an invasive procedure called
pulmonary artery catheterization. The special catheter used
for this purpose was the subject of a study published in 1970
by Swan, Ganz, and others. Since then, the catheter has been
marketed under the brand name Swan-Ganz, and the term
Swan-Ganz catheter has become synonymous with pulmonary
artery catheter. This catheter is a very thin, multilumen flexible
tube with a balloon located at its distal end. The balloon can
be inflated through a separate channel inside the catheter. The
catheter contains at least two additional internal channels: the
distal channel, leading to an opening at the tip of the catheter,
and the proximal channel, leading to an opening located several
centimeters back from the tip. Pressures can be measured or
blood can be withdrawn through these channels via the proxi-
mal and distal ports of the catheter (Figure 6-2).
A physician inserts the catheter under surgically sterile con-
ditions, sometimes at the bedside of a critically ill patient in a
hospital intensive care unit. Proximal and distal channels are
first filled with sterile fluid to remove all air; the catheter is then
inserted into a large systemic vein, usually the right internal
jugular or subclavian vein, and advanced until the tip enters the
right atrium. At this point the balloon is inflated, allowing the
bloodstream to direct the catheter tip across the tricuspid valve
into the right ventricle-hence, the term flow-directed, ball_oon-
tipped catheter. The physician advances the catheter until the
bloodstream carries it through the pulmonic valve and into the
pulmonary artery (Figure 6-3). During insertion, press_ures at
the catheter tip are continuously recorded by an elec~romc pre~-
sure transducer connected to the distal port. The stationary flmd
column inside the distal channel reflects these pressures pre-
cisely because it is in direct contact with the blood a~ the cathe-
ter's tip. The pressure waveforms are continuously d'.splayed on
the bedside monitor as the catheter is advance~; this helps the
physician identify the position of the catheter tip because each
cardiovascular structure produces unique pressure waveforms
(Figure 6-4, A and B).
When the catheter is advanced far enough to wedge in a small
branch of the pulmonary artery, the inflated balloon completely
blocks blood flow to the downstream vessels supplied by that
artery (see Figure 6-3, dotted circle). The pressure measured from
the catheter tip in this wedged position is called the pulmonary
capillarywedgepressure (PCWP). (When the balloon is deflated,
flow resumes, and the catheter tip simply measures the pulmo-
nary artery pressure [PAP].) The vessels extending beyond the
artery blocked by the inflated balloon are in direct communica-
tion with the pulmonary capillaries and the pulmonary veins.
Pulmonary venous pressure is nearly equal to left atrial pressure
(LAP), which is essentially equal to left ventricular end-diastolic
pressure (LVEDP), the pressure inside the filled ventricle just
before it contracts (see Figure 6-3). This so-called filling pressure
is also known as preload of the left ventricle. The PCWP is only
slightly greater than the filling pressure of the left ventricle. 3 The
PCWP accurately reflects changes in LAP (or ventricular filling
pressure) because the stationary fluid column inside the catheter
is functionally extended from the catheter tip to the left atrium.
For this reason, the PCWP is commonly used to assess the pump-
ing function of the left ventricle. For example, if the left ventricle
fails to contract with normal force, blood flowing into it dams up
in the left atrium, pulmonary veins, and capillaries; consequently,
the PCWP increases. In certain rare circumstances, the PCWP
might not accurately reflect left atrial pressure: ( 1) if the pulmo-
nary veins constrict and downstream resistance beyond the cath-
eter tip increases or (2) if the catheter tip is in an area in the lung
where alveolar pressure exceeds pulmonary venous pressure, as
might occur in positive pressure mechanical ventilation. In the lat-
ter instance, high alveolar pressure compresses capillaries distal to
the catheter tip, blocking its communication with the left atrium.
CONCEPT QUESTION 6-2 - - - r ..,-; -#,
'-', .
Why would a narrowed (stenotic) mitral valve affect the
PCWP? (See Figure 6-3.)
 114 SECTION I The Respiratory System

Pulmonary
artery

Left
__,__-I-~-- atrium
Right
atrium
4<~...\---f----lf-- Mitral
valve
Tricuspid Right Left _---4,......i,.___ open
valve --'l----::=::- __,_ _ ventricle ventricle
open

Systemic
circulation
Figure 6-3 Pulmonary artery catheter in place. The dotted circle represents the wedge position. The heart is in diastole in this schematic. (From
Martin L: Pulmonary physiology in clinical practice, St Louis, 1987, Mosby.)

RA RV PA PAWP

40
RA RV PA PAWP mm Hg

B 0
. Correlation between pulmonary artery catheter positions (A) and pressure waveforms (B) RA Right at • RV, right v t · I . PA.
F1gure 6-4 . . · , num;
artery· PA WP, pulmonary artery wedge pressure. (From Wilkins RL, Stoller JK, Kacmarek RM: Egan'sfiund e_n nc e, · '
puImona ry , amen ta 1s of respiratory care,
ed 9, St Louis, 2009, Mosby.)
 CHAPTER 6 Pulmonary Blood Flow 115

sample for purposes of measuring the average venous oxygen

CLINICAL 6l content of the body. A thoroughly mixed venous blood sample
FOCUS - reflecting the true average venous oxygen content of the body
must be obtained from the pulmonary artery, through the dis-
Causes of Pulmonary Artery Catheter Pressure
tal channel of the catheter (see Figure 6-2). By comparing the
Waveform Shapes ,
oxygen content of mixed venous blood with the oxygen content
Proper positioning of the pulmonary artery catheter is con- of systemic arterial blood, the oxygen consumption of the body
firmed by waveform patterns produced as the catheter is can be assessed. (This is discussed in Chapters 8 and 12.)
advanced into the pulmonary artery (see Figure 6-4). The By measuring and comparing pressures obtained from
first waveform appears on the monitor when the tip of the the pulmonary artery catheter (RAP, PAP, and PCWP), the
catheter reaches the great vessels. This is known as the cen-
tral venous pressure (CVP) and reflects pressure in the vena
cava and right atrium . A normal value for CVP is about 2 mm
Hg; this produces the low-amplitude waveform in Figure 6-4, CLINICAL 62
8. In the right atrium, the balloon is inflated for two reasons:
FOCUS -
(1) to decrease the risk of cardiac arrhythmias induced by the Differentiating Causes of High Pulmonary
catheter tip hitting the ventricular walls and (2) to allow blood Artery Pressure
flow to catch the balloon and carry the catheter forward .
You have two patients with the following cardiac pressure
The catheter passes through the tricuspid valve into tne
right ventricle. The pressure waveform increases in height values.
as the ventricle contracts (systole) and decreases sharply
to near 0 as the ventricle relaxes (diastole) (see Figure 6-4
Patient A
; Pulmonary artery (PA) systolic 38 mm Hg
8) . During diastole, the pressure waveform slowly rises
PA diastolic 25 mm Hg
blood flows into the right ventricle through the tricuspid
Pulmonary capillary wedge pressure (PCWP) 21 mm Hg
valve. Normal right ventricular pressure is about 25/0 mm Hg ,
(systolic/diastolic).
Patient B
The striking difference between pulmonary artery pres-
PA systolic 40 mm Hg
sure (PAP) tracings and tracings created by the right ventricle
PA diastolic 25 mm Hg
is the diastolic pressure in the pulmonary artery. Closure of
' PCWP 10 mm Hg
the pulmonic valve prevents PAP from decreasing as much
· Although both patients have elevated pulmonary artery
as it does in the right ventricle (see Figure 6-4). The ejection
pressures (PAPs), the reasons for this are quite different.
of blood from the right ventricle creates a steep rise in the
, The PCWP helps differentiate origins of high PAPs.
systolic portion of the curve. After systole, PAP decreases
sharply until the pulmonic valve closes. Closure of this
Discussion
valve abruptly stops blood backflow, creating a shock wave
In the following discussion, PCWP is used as a substitute for
responsible for the dicrotic notch on the downslope of the
the_ left atrial pressure (LAP). PCWP (i.e., LAP) is elevated in
wavefor.m. Normal PiiPs are about 25/10 mm Hg.
Patient A and normal in Patient B. Pulmonary artery end-dia-

As the catheter floats into a small branch of the pulmo-
nary artery, the inflated balloon blocks blood flow. The pres-
sure tracing is similar to right atrial waveforms but is pf even ,
lower amplitude; this is known as pulmonary capillary wedge
pressure (PCWP). Normal PCWP is 4 to 12 mm Hg and is
about the same as pressure in the left atrium . If pulmonary
vascular resistance (PVR) is normal, the pulmona(Y artery
diastolic pressure is about equal to the PCWP.
The pulmonary artery catheter also can be used to assess
right ventricular preload and pumping function because the
proximal channel (see Figure 6-2) communicates with the right
atrium. The pressure measured at the catheter's proximal port
reflects right atrial pressure (RAP), sometimes called central
venous pressure (CVP).
Blood drawn from the proximal channel is a mixture of
superior and inferior vena cava venous blood. Because oxygen
contents of these two sources may differ considerably, proximal
channel blood is not a clinically acceptable mixed venous blood
I
stolic pressure (PAEDP) in Patient A is only 4 mm Hg higher
than PCWP, whereas PAE DP in Patient . B is 15 m H
higher than PCWP. In healthy people, the PAEDP . g
I equal to the PCWP (PCWP - LAP
-
is a most
) because pressures across
the. pul~onary capillary bed have enough time to equalize
• during diastole. High pulmonary vascular resistance (PVR)
cre~tes an mcreased PAEDP-PCWP difference because the
,.,,
re~1stance is l~cated between the pulmonary artery and left i
1
'' atrium.
h· In Patient B, . PVR must be h'igh , as s,h.own byt he
1
igh PAEDP-PCWP difference . The normal PCWP in Patient
B suggests normal left ventricular pumping action. In Patient
A, PVR must be normal because the difference between
PAEDP_and PCWP is small. The elevated PCWP (i.e. LAP) is
transmitted back acr oss th e pulmonary cap1llanes
. . '
. creating a
p~oportionately high PAEDP, preserving the PAEDP-PCWP
difference . Causes of increased PAP in Patient'A may be left
ventricular pumpi'n g f a1·1 ure or rnitral
• ,.
_ valve narrowing. Causes
of increased PVR in Patient B may be a pt lmonary embol~s
or vasoconstriction induced by hypox'emia , ' '
116 SECTION I The Respiratory System

clinician can evaluate right and left ventricular function, dif- Clinically, values for calculating PVR are o~tained fro1:1
ferentiate the causes of increased PAP, and assess the risk of pulmonary artery catheter measurem~nts. Cardiac ou~put 1s
pulmonary edema. PAP might be increased because of exces- obtained via the thermodilution techmque, and PCWP IS sub-
sive blood volume (hypervolemia) or because ofleft ventricular stituted for LAP. A microprocessor computes the mean PAP
pumping failure in which blood dams up in the entire pulmo- from the p AP waveform. The clinical equation is as follows:
nary circulation. The PAP might also be increased as a result mean PAP - PCWP
PVR= .
of increased pulmonary vascular resistance (PVR). Increased Ot
pressures in either ventricle at the end of diastole, coupled with For example, at a Q1 of 5 L per minute, a mean PAP of 14 mm
a low cardiac output, signal a loss of ventricular pumping abil- Hg, and a PCWP of8 mm Hg, PVR is calculated as follows:
ity, or a loss of contractility. Increased PCWP, regardless of the 14 mm Hg - 8 mm Hg = 1.2 mm Hg/(L/min)
cause, means that the pulmonary capillaries are engorged with 5 L/min
blood, increasing the likelihood that fluid will be forced into A pressure of 1.2 mm Hg is needed to pr?duce a flow_ of 1 L ~er
interstitial lung spaces and cause pulmonary edema. Under- minute through the pulmonary circulation. In classic physics,
standing these relationships is essential for taking appropriate pressure is measured in dynes per square centimeter (force per
therapeutic actions. unit of area), and blood flow is measured in milliliters per sec-
ond (cubic centimeters per second). Using these measurement
Measurement of Pulmonary Blood Flow or Cardiac Output units, PVR is calculated as follows: 2
The amount of blood the heart pumps each minute can be clini- 2
dynes x sec d
cally measured with a pulmonary artery catheter via a thermo- dynes/cm
~----,---
3
dynes sec
=- -
2
x - -3 = -------=--
5
= ynes •sec• cm -s
dilution technique. In this method, a known volume of room cm /sec cm cm cm
temperature fluid (e.g., saline) is rapidly injected into the right The resistance term dynes • sec• cm- 5 is traditionally used in
atrium through the proximal injection port (see Figure 6-2) . clinical hemodynamic measurements. To convert mm Hg/(L/
This volume of cool fluid rapidly flows into the right ventricle min) to its equivalent units in dynes •sec• cm- 5, one multiplies
where it is pumped into the pulmonary artery. A temperature- mm Hg/(L/min) by 80. Thus, the PVR of 1.2 mm Hg/(L/min)
sensing thermistor near the end of the catheter (see Figure 6-2) calculated previously is equivalent to 96 dynes • sec• cm- 5.
in the pulmonary artery records a sudden decrease in tempera- The pressure difference between beginning and ending
ture as the bolus of cool saline passes by. If cardiac output is points of the systemic circulation is the difference between
increased, blood temperature rapidly returns to its original mean arterial pressure (MAP) and RAP (or CVP) . Systemic
value; if it is decreased, the temperature increases more slowly to vascular resistance (SVR) is calculated as follows ( using values
the original value. A microprocessor receives information from from Figure 6-1) :
the thermistor and computes the area under the temperature-
time curve. The area under the curve is small for rapid blood SVR = MAP <lt RAP
flow and large for slow blood flow. The microprocessor uses
the area under the curve and the volume of the injected flpid
SVR = -r =
93* 2
18.2 mm Hg/(L/min)
. A pressure gradient of lS.2 mm Hg is needed to drive 1 L per
to compute the blood flow rate, or the cardiac output (Qt) .
mmute of blood through the systemic circulation (compared with
Several determinations of cardiac output can be made within
1.2 mm Hg in the pulmonary circulation). This pressure converts
minutes in this fashion.
to about 1456 dynes • sec • cm- 5• PVR is normally less than one
1
tenth of SVR. Thus, right ventricular work is about one tenth of

I PULMONARY VASCULAR
RESISTANCE
left ventricular work, which explains why the left ventricular mus-
cle mass is normally much greater than the right ventricular mass.
PVR is measured in millimeters of mercury per liter per minute
(mm Hg/[L/min]). PVR is the resistance that the vessels pose
CONCEPT QUESTION 6-3 , .Ji«'. ~·
to blood flowing through the pulmonary circulation-it is the Which of the following does an increased PVR influence more:
resistance against which the right ventricle pumps. Any fac- PAP or PCWP? Explain.
tor that increases PVR increases right ventricular work. An
increased PVR does not affect left ventricular work because this
ventricle is situated on the downstream side of the pulmonary Dist_ribution of Pulmonary Vascular
Resistance
vessels.
Figure 6- 1_ shows that the pressure decreases from the pulmo-
Calculation of Pulmonary Vascular Resistance nary arterioles to the pulmonary capill . h
. . . anes to t e pu1monary
vems are similar-that is from 12 m H H
PVR is calculated by dividing the mean pressure differ_ence ' m g to 10 mm g to
. run·g and ending points of the pulmonary ctrcu-
b etween b eg Ill . . ' MAP is estimated by doubling diastoli . . .
· b th lmonary blood flow. This 1s shown as follows: pressure and dividin b 3. (Norm . c pr~ss~re, ~ddmg this value to systolic
lat10n Y e pu mean PAP - LAP
systolic time ) In th"g y h al diaSlo!,c trme Is approximately double the
PVR(mm Hg/[L/min ])= Ot . 1s examp Ie, t e approXIm t MAP .
(120 + 2(80)]/3 = 93_ 3 mm Hg. ae 1s calculated as follows:
 p"
CHAPTER 6 Pulmonary Blood Flow 117

9 mm ~g as shown ~n right lung of the diagram in Figure

6- 1. This means the md1V1dual resistances of these three com-
ponents are nearly equal; at rest, each accounts for about one
thir~ of th~ total PVR. In contrast to the more muscular sys- Alveolar
temic artenoles, pulmonary arterioles do not normally function capillary
to regulate and redistribute blood flow. 4 In contrast to the pul-
monary vasculature, systemic arterioles account for about two A
thirds of the total SVR.

I FACTORS AFFECTING PULMONARY

VASCULAR RESISTANCE
A p
Passive or active factors may change pulmonary vessel diam-
eters and vascular resistance. Passive changes occur in response
to pressure differences across vessel walls. Because pulmonary
vessels are thin and distensible, they are especially susceptible to
pressure-induced diameter changes. Active changes in the ves-
sel diameter and resistance occur when vascular smooth muscle
contracts or relaxes.

Passive Factors
Lung Volume: Effects on Alveolar and Extraalveolar
Vessels
Pulmonary vessels can be classified into two groups: vessels in
direct contact with alveoli, exposed to alveolar pressure (alve-
olar vessels), and vessels not in contact with alveoli, exposed
to intrapleural pressure (extraalveolar vessels). Alveolar ves-
sels are pulmonary capillaries in intimate contact with alveolar
walls. The state of alveolar inflation determines the diameters
of alveolar vessels. As the lung inflates, alveolar vessels are com-
pressed, and their resistances increase (Figure 6-5, A and B). 1·3
Extraalveolar vessels include all pulmonary arteries, arteri-
oles, venules, and veins not in direct contact with alveoli. The
lung's elastic fibers have a tethering effect on these vessels (simi-
lar to their effect on small airways), stretching them to larger
diameters as the Jung inflates. In addition, during lung infla-
tion, subatmospheric intrapleural pressure increasingly dilates
these vessels, decreasing their resistance. 1·3 Extraa~~eolar ves-
sels also include certain capillaries between alveoli m corners
formed by the junctions of adjacent alveoli (see Figure 6-5, A
and B). As the lung inflates, these corner spaces enlarge, stretch-
ing and dilating the "corner vessels" (see Figure 6-5, B).
To visualize this phenomenon, think of a basket of_small half~
inflated balloons. Similar to the balloons, the sphencal alveoli
touch each other, but spaces exist betw~en ~he~. ~xtraalveolar
corner vessels occupy these spaces. Dunng msp1rat1on, the bal-
loons (alveoli) enlarge, increasing the amount of sp_ace between
them. Alveolar recoil forces attempt to increase this space fur-
ther. The pressure in these spaces decreases, dilating the corner
vessels and reducing their resistance.
Because aIveo1ar an d extraalveolar vessel. . resistances are in
1
series with each other, their effects are add1t1ve. Thus, t~ta 1PVR
is th e composite
· o f alveo Jar and extraalveolar vessel resistances,
. regions of the lungs are completely collapsed. 1.4 As intravas-
creating a U-shaped curve (Figure 6-6). Overall, PVR 1s low-
est at fu nct1ona
• 1res1"d uaI capacity (FRC). At volumes. . less than
. il c
FRC , e1astIC retract e 1orce s and subatmosphenc mtrapleural
B t
Figure 6-5 Schematic drawing of alveolar and extraalveolar (corner)
vessels during normal, quiet inspiration (A) and deep inspiration (B).
High lung volumes (B) compress alveolar vessels and dilate extraal-
veolar vessels. A, Alveoli; P, pleural pressure. (Redrawn from Fishman
AP: Assessment ofpulmonary function, New York, 1980, McGraw-Hill.)
pressures are weak, allowing extraalveolar vessels to narrow,
shorten, and kink. The resulting increase in extraalveolar ves-
sel resistance predominates, increasing total PVR. At volumes
gre~ter than FRC, i~creased alveolar vessel resistance caused by
~ap1llar:r compression becomes the predominant factor, again
mcreasmg total PVR (see Figure 6-6).
Vascular Pressure: Recruitment and Distention
An increase in either PAP or LAP decreases PVR. One reason
is that both PAP and LAP cause an increase in distending pres-
sure across vessel walls (transmural pressure), which dilates
1
them. .4 This dilating effect is amplified if PAP and LAP increase
together (Figur~ 6-7). 1·3 For example, consider an increasing
LAP caused b! madequate left ventricular pumping action; the
ele~ate~ LAP 1s reflected back throughout the pulmonary veins,
cap1llanes, and arteries, dilating them and decreasing their vas-
cular resistance.
The second mechanism responsible for the decrease in PVR
when vascular pressures increase is recruitment. 1•4 Under nor-
ma! resting conditions, some pulmonary capillaries in the upper
cular pressure increases, these collapsed capillaries are forced
open (recruited), increasing the total cross-sectional area of the
pulmonary capillary bed. As vascular pressures increase further,
 118 SECTION I The Respiratory System

of mercury. The opposite effect is equally important; decreased

cardiac output and vascular pressures cause derecruitment, or
collapse, of pulmonary capillaries.

t CONCEPTOUEST~
In what circumstance may a decreased cardiac output be
associated with increased pulmonary vascular pressures and
pulmonary capillary distention?
Total
Blood Volume
Pulmonary blood volume is generally constant, but it may
change under certain circumstances. For example, a sustained
Valsalva maneuver (forced expiration against a closed glottis)
Alveolar
can squeeze 250 mL of blood into the systemic circulation. 3 Sys-
temic blood loss can also decrease pulmonary blood volume.
Left ventricular failure causes blood to dam up in pulmonary
Extraalveolar vessels, potentially increasing pulmonary blood volume by
100%. 3 Regardless of the mechanism, increased blood volume
RV FRC TLC distends and recruits capillaries, decreasing the PVR.

Vital capacity -

Figure 6-6 Relative changes in alveolar vessel, extraalveolar vessel, and

Active Factors fll
total pulmonary vascular resistance as the lung volume increases. RV, Neurogenic Stimuli -~
Residual volume; FRC, functiona l residual capacity; TLC, total lung There is little evidence to suggest that neurogemc stimuli play
capacity. (Redrawn from Murray JF: The normal lung, ed 2, Philadel- a role in controlling pulmonary blood flow in healthy adults. 1·4
phia, 1986, Saunders.) Although sympathetic and parasympathetic nerves inner-
vate the pulmonary vasculature (mostly larger arteries), their
functional significance is marginally important and not well
30
understood.' Some investigators have shown that sympathetic
a, stimulation causes a slight increase in PVR, but others have
"
C:
shown only a stiffening of the arteries with no change in calcu-
·u; lated resistance.• Parasympathetic (vagal) stimulation causes
e a slight decrease in vascular resistance, but its physiological
:;;
:, 15 significance is unknown. Overall, the effects of autonomic
"'"'"> stimulation on the pulmonary circulation are controversial
c:- and not well understood; autonomic stimulation produces
"'
C:
0
LAP= 14
only minor changes in the smooth muscle tone of vessels in
E
:, the adult lung. 1
0..

0 Humoral Agents and Nitric Oxide

20 25 30
The most i'.11p~rt~nt substance that regulates pulmonary vas-
Pulmonary arteri al pressure cular tone 1s mtnc oxide (NO), derived from the endothelial
figure 6-7 Effects of pulmonary artery pressure changes on pulmo- cells lining the blood vessels.5 Naturally occurring (endog-
nary vascular resistance. High left atrial pressure (LAP) exaggerate_s _the e_nous) h~moral_ substances in the body produce vasodila-
effect. (From Berne RM, Levy MN: Physiology, internattonal ed1t1on, tIOn by s'.1mulatmg the production of NO, previously called
ed 2, St Louis, I 988, Mosby.) endothelium-derived relaxing factor (EDRF). Endogenous
substan~es include acetylcholine, bradykinin, histamine,
individual capillaries widen or distend, decr_eas!ng PVR even thrombm, s~ro:onm, adenosine di phosphate (ADP), and some
more. If vascular pressure increases from an m1tially low level, prostaglandms. In 1987, Furchgott6 noted that acetylcholine
recruitment is the chief mechanism whereby PVR decrea~es; did_ not cause _smooth muscle relaxation in vessels stripped of
"f vascular pressure increases further from an mi- theu endothehum; he postulated that endothelial cells produce
converseIy, 1 d" · ·
. ]I hi h level when all vessels are already ?pen, 1stent~on 1s a sm~oth ~uscl~ relaxing factor. Palmer et al.7 and Jgnarro
tta Y _g
the mam reason w
hy PVR decreases. 4 Recruitment and d1sten-
. . A
etaL later identified EDRF as NO. The 1998 Nobel Prize in
I · hy p AP changes little dunng exercise. scar- phys1ology or medicine was awarded to Furchgott Jgnarro,
rion help exp am w ecruitment and distention dramatically and Murad for their discovery of the role of NO in the human
• output increases, r
d iac . .
II . PAP to increase only a few m1lhmeters body. 9
decrease PVR, a owmg

Acetylcholine
Bradykinin
ADP
Histamine
Shear stress
Pulmonary arteriole
Figure 6-8 Endothelial production of nitric oxide (NO) in the pulmonary arteriole. Various stimuli may activate endothelial surface receptors,
in itiating a chain of biochemical events that produce NO and subsequent vascular smooth muscle relaxation. ADP, Adenosine diphosphate; cNOS,
constitutive nitric oxide synthase; cGMP, cyclic guanosine monophosphate.
Nitric oxide is a potent vasodilator in the human circula-
tion, and it plays an important role in regulating pulmonary
vascular smooth muscle tone.5 The endogenous substances
previously listed are considered to be endothelial-dependent
vasodilators because they depend on the endothelial release of
NO for their effects. The elaboration of NO accounts for the
vasodilating mechanism of nitrate drugs such as nitroglycerin
(used to improve coronary blood flow) and nitroprusside (used
to treat dangerously high blood pressure). 10
NO is produced in vascular endothelial cells (Figure 6-8) by
oxidation of an amino acid, L-arginine, catalyzed by an enzyme,
nitric oxide synthase (NOS). 11 · 13 As stated in Chapter I, there
are three forms of NOS: neuronal NOS (nNOS), which is con-
stituted in nonadrenergic noncholinergic neurons (a form of
constitutive NOS [cNOS)); inducible NOS (iNOS), which is
induced in airway epithelial cells by inflammation; and endo-
thelial NOS (eNOS), another constitutive form of NOS that
is generated in vascular endothelial cells (referred to as cNOS
in Figure 6-8).s.u Production of eNOS is controlled by e~do-
thelial cell surface receptors that are stimulated by the vanous
humoral substances previously listed. Besides these substances,
mechanical factors such as stretching and shear stress stimu-
late cell surface receptors.11 Whether the stress is humoral or
mechanical, receptor stimulation activate_s eNOS_ but only m
the presence of calcium ions (Ca++). Calcmm:act1vated cNOS
catalyzes the oxidation of L-arginine, producing small bursts
of NO.
NO is highly soluble in cell membranes and diffuses instantly
into vascular smooth muscle cells. In vascular smooth muscle
cells, NO activates another enzyme, guanylate cyclase, which
catalyzes the production of cyclic guanosine monophosphate
(cGMP), as shown in Figure 6-8. cGMP causes vascular sm~oth
muscle relaxation. Physical exercise induces cNOS production,
presumably by increasing vascular_press~re, ~nd may be a fac-
tor, along with recruitment and d1stent10n, m preventing sig-
11
nificant increases in PVR during exercise.
CHAPTER 6 Pulmonary Blood Flow 119
Smooth
muscle
Predict the physiological effect of a drug that inhibits the
action of NOS.
Endothelial cells synthesize NO in small amounts on
demand, exerting a regulatory vasodilating influence on pul-
monary arterioles under normal resting conditions.11,12 A
calcium-independent form of NOS (inducible NOS [iNOS)) can
be induced in endothelial and inflammatory cells by endotoxins
associated with bacterial blood infections (septicemia) and by
various other inflammatory mediators in the body.5 In contrast
to eNOS, which is released in small pulses as needed, iNOS is
always "turned on," releasing large, continuous amounts of NO
not controlled by cell receptor-dependent mechanisms. Exces-
sive induced NO production is linked to the massive vasodilation
and hypotension of septic shock syndrome. 14 ,15 Sepsis-induced
vasodilation does ~ot_ r~~pond well to vasoconstrictor drugs. If
an effective 1NOS-mh1b1tmg drug could be given to patients with
septic shock, it would seem that the vasodilation and associated
hypotension migh_t be reversed, increasing the blood pressure.
This hypothesis was studied in a large multicenter clini-
cal trial in which humans with septic shock were given a drug
known to inhibit NOS activity. The NOS inhibitor reduced
blood nitrate levels, increased pulmonary and systemic vascu-
lar tone, maintained systemic blood pressure in an acceptable
range, and reduced the need for conventional vasoconstrictor
drugs, such as norepinephrine. 14 However, overall patient out-
come was not improved. Although general inhibition of NOS
is not ultimately beneficial in septic shock, selective inhibition
of the inducible form (iNOS) was found to be more beneficial
than norepinephrine in an animal study. 16
Inhaled NO gas in extremely low concentrations has been
used therapeutically to treat severe pulmonary hypertensio n
and to selectively dilate pulmonary vessels in well-ventilated
 120 SECTION I The Respiratory System

regions of the lungs. In the latter instance, inhaled NO of neces-

sity enters the best-ventilated lung areas, selectively lowering 600
vascular resistance in those regions. Because blood flow follows
the path of least resistance, it is diverted from poorly ventilated 500
to well-ventilated areas. NO inhalation has been especially ben-
eficial in treating infants with persistent pulmonary hyperten- 400
sion of the newborn (PPHN) (see Chapter 16). a:
>

\
<l.
300
Chemical Factors pH
The most important chemical factor causing pulmonary vasocon-
200 7.1
striction is low alveolar oxygen pressure (PAO 2)-that is, alveolar
hypoxia. A PA 0 2 of less than 70 mm Hg usually elicits this effect,
known as hypoxic pulmonary vasoconstriction (HPV). 1 HPV 100 7.2
is brought about by alveolar hypoxia, as opposed to arterial or 7.3
mixed venous hypoxemia. The elements of the vasculature that 0 "-- -~ 7.4
constrict are predominantly the small precapillary arterioles; small
pulmonary veins also constrict to some extent but produce only 25 50 75 100
20% or less of the HPV-induced increase in PVR. 17 This constric-
P0 2 mm Hg
tive venous response might explain the acute pulmonary edema
sometimes seen in individuals who travel to high altitudes in the
mountains where atmospheric oxygen pressure is low; hypoxia- Figure 6-9 Effects oflow arterial pH and hypoxemia on pulmonary vas-
cular resistance (PVR) in newborn calves. The greater the acidemia, the
induced venous constriction could increase pulmonary capillary
greater the vascular resistance at any PO 2 value. Note the abrupt increase
pressure, which is a feature of high-altitude pulmonaryedema.17
in PVR at PO, less than 50 mm Hg, especially at pH less than 7.40. (Re-
The constrictive response to hypoxia is unique to the pulmo-
drawn from Rudolph AM, Yaun S: J Clin [nvest45[3]:407, 1966.)
nary circulation; hypoxia evokes vasodilation in the systemic
circulation. High PAO 2 (hyperoxia) has little effect on normal
pulmonary circulation, probably because pulmonary vessels awa~ from poorly ventilated, hypoxic regions to the better
in normal lungs have little muscle tone, and their vasodilating ventilated areas. If HPV or a similar mechanism did not exist,
ability is minima!. 18 However, in hypoxic individuals, improved pulmonary arterial blood would remain poorly oxygenated as
oxygenation markedly dilates pulmonary vessels and dramati- it flows ~nchecked past underventilated alveoli. This blood
cally decreases PVR. wou!d mix with and decrease the PO 2 of blood leaving well-
HPV is enhanced by low arterial blood pH (acidemia); ventilated alveoli, causing systemic arterial hypoxia. Thus,
HPV becomes progressively greater for a given PAO 2 as pH HPV has .a beneficial effec t , even t h ough 1t
· mcreases
· the PVR ·
decreases. At a normal arterial pH of 7.40, the maximal vaso- If th e ~nti~e lung is uniformly hypoxic ( e.g., at high altitudes),
18 HPV
constrictive response occurs at a PAO 2 of 60 to 70 mm Hg ; this . 1s widespread th roug h out t h e l ung, increasing vascu Iar
corresponds with a PaO2 of about 50 to 60 mm Hg when the resistance
h l f b and pressu res. HPV st1.11 may be physiolog1ca . IIY
normal alveolar-to-arterial PO 2 gradient is taken into account. e pdu 1 ecause elevated pressures recruit previously nonper-
A classic animal experiment showed that at arterial pH less f use pu1monary capilla nes,. mcreasmg
. . the surface area for gas
than 7.30, a PaO 2 less than 50 mm Hg causes a sudden, sharp exc h ange.
increase in PVR (Figure 6-9). 19 At a normal PaO 2, arterial pH
must decrease to less than 7.25 to cause a significant increase
in PVR. 18 High PaCO 2 increases PVR indirectly by generating
Ci·M@a#d•)•lfiU·l§i#, 2)
Sc,nt,photography a . . .
carbonic acid, which causes acidem ia. HPV is also enhanced by . ' spec,a1imaging technique allows venti-
1att1on or blood flow distribution to be seen in th~ lungs (venti-
NOS-inhibiting agents, suggesting that reduced endothelial NO la ion or perfusion sea ) Wh
17
release may be an underlying mechanism in HPV. caused by ns · Y does regional alveolar hypoxia
mucous plugging prod . .
HPV is inhibited by various mediators present in the blood to one produced b uce a perfusion scan s,m,1ar
that cause vasodilation, such as the endothelial-derived sub- pulmonary fl Y a pulmonary embolus that blocks blood
stances NO and prostacyclin. 17 HPV is also inhibited by drugs that ow, and how might one d . .
these two conditions? 1stmguish between
block alpha-adrenergic or stimulate beta-adrenergic receptors. In
addition, it is inhibited by increased LAP (a vascular distending
17
effect), high alveolar pressure, and high blood pH (alkalemia). Mechanism of Hypoxic Pulmona . .
The exact mechanism of HPV _ry Vasoconstrr ct1on
1
response is localized . is poorly understood. The
Physiological Function of Hypoxic Pulmonary , occurring onl · .
HPV does not dep d Ym areas of alveolar hypoXla.
. en on nervous h
Vasoconstriction 1t occurs in surgical! or umoral control because
. Y removed h •
The physiological function of HPV is to match bl~od flow ventilated with hyp . . ' mec amcally perfused lungs
OXJc gas mixtu 11 . h. .
with ventilation better (i.e., to divert pulmonary arterial blood occurs even in patient h res , t 1s explams why HPV
sw orecei ve h eart-lung transplants.
 CHAPTER 6 Pulmonary Blood Flow 121

CLINICAL 6-3 by inhibiting potassium ion (K+) channels, which is accompa-

FOCUS nied by the opening of ca++ channels and Ca++ entry into ~e
cen.1, 17 Ca++ are essential in the smooth muscle contraction
Chrome Hypox1a'and Right Ventric'ular failure
f 1 • \
i process. Consistent with this proposed mechanism is the fact
that Ca++ channel blocking drugs inhibit HPV, whereas Ca++
Yo):l are called to assess a patient admitted with chronic
obstructive pulmonary disease (COPD) . A physician' has
1 agonists enhance it. 1
just examined the patient and tells you that physic~! ,find-
ings include obvious pulmonary disease, distended neck i
Loss of Hypoxic Pulmonary Vasoconstriction
The HPV response is often diminished in patients with acute
veins, ankle edema, and hepatomegaly (enlarged liver).
lung injuries, such as burn and smoke inhalation, sepsis, and
~rterial blood gas values indicate chronic hypoxia, and the ,
acute respiratory distress syndrome (ARDS). 13·14·17·21 ·22 This
Lchest radiograph shows hyperinflation of the lungs with right ·. diminished response may account for the severe systemic hypox-
yentncular enlargement (hypertrophy). The admitting diagno-
emia these diseases cause. Acute lung injury causes the release
Lsis is COPD with right ventricular hypertrophy . What is the ,
of inflammatory mediators that induce formation of iNOS and
Lrelationship between this patient's lung disease and cardiac subsequent NO release; this prevents the normal vasoconstric-
!function?
tive response of vessels in hypoxic lung regions. When the HPV
lDiscussion
Chronic hypoxia characterizes COPD. COPD is often associ-
response is lost, poorly oxygenated mixed venous blood flows
unchecked through underventilated and nonventilated lung
regions, creating severe shunting and systemic arterial hypox-
,ated with anatomical destruction of alveoli and associated
emia. This type of intrapulmonary shunting responds poorly
capillaries, decreasing the functional surface area tor gas to oxygen inhalation because the supplemental oxygen cannot
exchange. The resulting hypoxia induces pulmonary vaso- enter nonventilated alveoli.
constriction, increasing pulmonary artery pressure (PAP} ..) Inflammatory mediators are also released in response to
The destruction of the alveolar-capillary membrane area
I contributes further to increased PAP by reducing the cross- ·
bsectional area of the pulmonary vasculature. High PAP p9sEls f
overinflation of the alveoli, which has implications for patients
who are dependent on mechanical ventilatory assistance.
Patients with acute lung injuries often require positive pres-
"an increased opposition to blood tlo~ coming from the right , sure mechanical ventilation. High pressures during mechanical
t ventricle. The muscle mass of the nght ventricle increases 1
r i~ response to the increased workload, but it may ultimately,cl
ventilation can overstretch and injure the alveoli. This type of
stretch injury is known to release inflammatory cytokines that
r fail to pump blood effectively into the high-resistance pulmo- , induce iNOS and subsequent NO release, which counteracts
nary vascular system. A tailing right ventricle causes qlood 1 HPV.23.2s
to back up into the right atrium, vena cava, jugular veins, , A purely mechanical explanation for why acute lung injury
'. liver, and veins in the legs and ankles; this accounts tor\ , might diminish the effect of HPV also has been proposed. 21
t liver enlargement (hepatomegaly) and ankle edema :1pedal , Injury to the alveolar-capillary membrane increases its per-
t edema) . Right heart failure induced by pulm.onary di~~a~13.' meability, allowing fluid to enter the alveolus and deactivate
j 1s. called car pulmonale. Th'1s con d·t·
1 10 n often improves
_ with r. surfactant. The resulting high surface tension causes alveoli to
I continuous oxygen therapy, which relieves hyp~x1c vasocon- shrink and collapse. Animal studies using an in vivo microscope
. striction and decreases pulmonary vascular resi stance. ' revealed that as alveoli shrink, they place a tethering force on
the extraalveolar vessels, causing them to dilate. In this way,
portions of the pulmonary vasculature are mechanically dilated
Animal and human studies strongly suggest that _lac~of~;~ in injured, poorly ventilated lung regions, possibly negating or
minimizing the effects HPV might have. 21
mal NO release by the end~thelium playds athrol~\ 1:~s ~imin-
. d PO m vascular en o e ia
mec hamsm. Decrease 2_ d d NO formation is a Inhaled Vasodilators in Acute Respiratory
. h NO th . estmg that re uce
1s es syn es1s, sugg . b - h db breathing Distress Syndrome
. . HPV 1, 20 HPV 1s a o11s e Y
mechamsm underlymg · . l d thelial NO pro- Despite the reduction of the effectiveness of HPV in acute lung
stI
NO gas mixtures or by drugs ~at ~~ at~:;si:enhances HPV, injury, the overall PVR is nevertheless often elevated in ARDS. 17
duction.1, 20 Conversely, blocking N ynlatin effect on HPV,
For this reason, inhaled NO and other pulmonary vasodilators
which means that NO must have regu g 'thout hypoxia
holdmg . . . . h k 17 Even m persons WI ' have been used clinically to decrease PVR. Besides decreasing
its seventy m c ec · . . onary vasoconstric- PVR, an added benefit of inhaled vasodilators (as a gas or an
d . h'b' . NO thesis mduce pu1m
rugs m 1 1t1ng syn ted pulmonary vas- aerosol mist) is that they selectively dilate pulmonary vessels
tion, confirming that the normally oxygenad_ t d dilation.20
. tate of NO-me ia e only in well-ventilated lung regions, diverting mixed venous
culature is in a contmuous s C ++ try 1·nto the vascular blood to these areas. The effect is to match blood flow with ven-
O f HPV a en
Whatever .t he cause · .' d to cause muscle con- tilation better, reducing intrapulmonary shunt and improving
st be mvo 1ve .
smooth muscle ce ll mu posed whereby hypoxia arterial oxygenation-in effect, enhancing the benefits of HPV.
. 1 . has been pro
traction. A mechamsm . 't has been shown that Selective dilation occurs because inhaled vasodilators can enter
.
d1rectly ul ooth muse1e, 1
affects vase ar sm ll membranes, probably only ventilated portions of the lung.
hYPoxia . depolarizes . smoo th muse1e ce

\
 122 SECTION I The Respiratory System

include prostacyclin (PGI 2), si!denafil (Viagra), n_itroprusside,

th Alternatives to inhaled NO have been sought because of
h. ehcomplex technology associated with NO administration
ig NO costs, potential NO toxicity, and the failure of NO
to decrease ove~all mortality in patients with ARDS. 26 Some
of these alternative vasodilators, which are inhaled as aerosols,
CLINICAL B4
FOCUS - both pulmonary and systemic blood pressures if given intra-
Different Therapy for Different Causes of
Increased Pulmonary Artery Pressure
Increased pulmonary artery pressures (PAPs) occur for dif-
ferent reasons. What are the different reasons, and how
does therapy differ?
Discussion
When _PAP is elevated as a result of high pulmonary vascu-
lar resistance (PVR), therapy is aimed at reducing the PVR.
For example, if hypoxic pulmonary vasoconstriction (HPV)
in chronic hypoxemia causes high PVR and right ventricu-
lar strain, continuous oxygen therapy might be appropriate.
Oxygen therapy relieves the hypoxia, removing the stimulus
for pulmonary vasoconstriction.
An elevated PAP caused by left heart failure (i.e., loss of
left ventricular pumping action) may be treated with inotro-
pic drugs, which increase the heart's contractility and pump-
ing effectiveness. Diuretics decrease the blood volume by
enhancing urine production and reducing venous return to
the heart. Vasodilators decrease the resistance against
which the left ventricle must pump, allowing it to pump
blood more effectively.
Understanding the origins of elevated PAP is important
because treatment approaches are completely different for
different circumstances.
and nitroglycerin.26-28 Similar to NO, pr~stacyclm_1s synthe-
sized in the pulmonary vascular endoth~hal cells; 1t exerts its
effects by activating specialized endothelial receptors. Sildena-
fil exerts its effects by inhibiting phosphodiesterase, an enzyme
that deactivates cyclic adenosine monophosphate (cAMP);
cAMP is the intracellular substance responsible for smooth
muscle relaxation. Nitroprusside and nitroglycerin induce the
enzymatic release of NO. All of these NO alternatives reduce
venously or orally. Intravenous or oral administration of these
agents not only could dangerously lower the systemic blood
pressure but also indiscriminately dilate all pulmonary vessels;
this would hinder HPV and worsen intrapulmonary shunt and
hypoxemia. However, when administered by inhalation, these
vasodilators affect only the pulmonary circulation and only
in well-ventilated lung regions; this tends to preserve HPV in
poorly ventilated areas. 26
DISTRIBUTION OF PULMONARY&
BLOOD FLOW ,8
Gravitational and Pressure Effects:
Zones of Blood Flow
Because pressures in the thin, distensible pulmonary blood
vessels are low, gravity a~d ~res~ure~ surrounding the vessels
grea~ly affect blood flow d1stnbut1on m the lung. The effects of
gravity create three distinct zones of blood flow, as described in
the classic model byWest4 (shown in Figure 6-10). Blood enters
the lung at the hilum through the pulmonary artery. The same
average PAP of about 15 mm Hg is applied to arterial vessels in
all zo~es. Arteries in zone III (lung base) are about 12 cm below
~he htlum. Thus, the weight of a column of blood 12 cm high
is adde~ to the pressure in zone III vessels. A column of blood
12 cm high exerts a pressure of about 9 mm Hg, causing arterial (

8mm Hg
Zone!
24 PA> Pa> Py
-5 mm Hg
E
S-
C)
C:
.2
0
E
0
,::
0
.D 12
a,
>
0
.D
"'
a,
"
C:

1ll
i5

Zone Ill
0 pa>Py>PA

Fi ure _1 Gravitational effects create three zones of blood flow patterns in_the pulmonary circulation 2 . 1
._
g fl 6 0 d zone Ill has continuous flow. (From Berne RM, Levy MN: Principles ofphysio/og,v ed 2 5· one I has no flow, zone II has interm t
tent ow, an ,, , t Lams, 1996, Mosby.)

pressure in zoneHI to be 9 mm Hg higher than arterial pressure
in zone II (see Figure 6-10). Blood flows down into zone Ill
111th the aid of gravity.
In contrast, blood is pumped up into zone J (lung apex)
against gravitational forces. Zone I arteries are about 12 cm
above the main pulmonary artery, causing the arterial pres-
sures to be 9 mm Hg less than the arterial pressure in the main
pulmonary artery. Figure 6-10 shows an upright lung (i.e., the
person is standing). If the person is supine, zones I to III are
redistributed from anterior to posterior lung regions, rather
than from the lung apex to the lung base. 4
Zone I Blood Flow
To illustrate zone I conditions, which are not normally pres-
ent in spontaneously breathing individuals, the lung model in
Figure 6-10 is receiving positive pressure mechanical ventila-
tion such that the average alveolar pressure is about 8 mm Hg
in all alveoli. In the lung apex or zone I, gravitational effects
cause both arterial and venous pressures to be lower than alveo-
lar pressure. Consequently, alveolar pressure compresses the
surrounding capillaries, totally occluding them and stopping
blood flow. Only extraalveolar corner vessels may still have
some blood flow in this zone. In zone I, alveoli are ventilated
but have no blood flow, which constitutes alveolar dead space
ventilation. In spontaneously breathing healthy individuals
with normal cardiac outputs and blood pressures, arterial pres-
sures always exceed alveolar pressures, even in the uppermost
apical lung regions, and zone I does not exist. However, a severe
decrease in blood pressure can lower PAP so much that zone I
conditions are created in the lung.
Zone II Blood Flow
Figure 6- IO shows that arterial pressure in zone II considerably
exceeds alveolar pressure, but alveolar pressure still exceeds
venous pressure; this produces intermittent flow through alve-
olar capillaries. Blood flows into a capillary at its arterial end
beca use its pressure exceeds the surrounding alveolar pressure.
A,, blood flows down the length of the capillary, approaching
th e venous end, capillary pressure progressively decreases until
it falls below alveolar pressure. At this point, alveolar pressure
collapses the capillary, stopping blood flow. (This is similar to
the situation described in Chapter 3 in which forced expira-
ti on causes dynamic airway compression after an equal pres-
sure point is formed.) The pressure of the stationary column of
blood in the capillary quickly equalizes with its source, the arte-
rial pressure, which is greater than alveolar pressure. This act10n
mo mentarily forces the capillary open, allowing blood flow to
resume. As blood flows through the opened capillary, pressure
again decreases down its length, falling below alveolar pressure,
recollapsing the capillary near its venous end. The cycle repeats,
ca using capillaries to flutter rapidly between open and closed
sta tes, producing intermittent flow. . . . mcreases cardiac output and PAP) recruiting any zone I to zone
The pressure gradient for blood flow ID zone II 1s the dif-
fe rence between arterial and alveolar pressure, not artenal and
venous pressure (as it is for most other vessels). As long as
venous pressure is below alveolar pressure, pulmonary ve.ms are
blocked, and venous pressures cannot influence flow. This zone
CHAPT ER 6 Pulmonary Blood Flow 123
CLINICAL 6-5
FOCUS
Most Likely Location of the Pulmonary Artery
Catheter Tip: Zone I, II, or 1117
Blood flow must be continuous between the tip of the Swan-
Ganz catheter and left atrium to reflect left heart pressure
accurately. Uninterrupted blood flow is found only in zone
Ill of the lung, where arterial and venous pressures exceed
alveolar pressures. Because the Swan-Ganz catheter is flow
directed (i.e., carried into place via continuous blood flow),
it is most likely to migrate into zone Ill. Pulmonary capillary
wedge pressure (PCWP) measured when the Swan-Ganz
catheter is located in zone I or 11 does not accurately reflect
left atrial pressure (LAP) because alveolar pressure momen-
tarily or continuously stops blood flow in these zones. PCWP
measured from zone I or II reflects alveolar pressures instead
of LAPs .
II flow characteristic is sometimes called the waterfall effect. In
this analogy, the rate of flow over the waterfall's edge is pro-
portional to the pressure difference between a point upstream
(arterial pressure) and a point at the waterfall's edge (alveolar
pressure). Neither the pressure in the stream below the water-
fall's edge (venous pressure) nor the height of the waterfall
influences the rate of flow over the edge.
Zone Ill Blood Flow
The arterial and venous pressures exceed alveolar pressure in
zone III because of the effects of gravity. Blood flow is contin-
uous and proportional to the difference between arterial and
venous pressures. As long as alveolar pressure is below vascular
pressures, it cannot influence blood flow. Gravity causes zone
III, the lung bases in the upright person, to have the greatest
blood flow.
Factors Affecting Zones of Blood Flow
Blood flow zones are not fixed, anatomical boundaries; rather,
they are dependent on physiological conditions. Certain respi-
ratory maneuvers, s~ch_ as exhaling against a closed glottis,
blo_w1~g through a wmd mstrument, or coughing, can momen-
~anly mcrease a_l~eolar pressures above arterial pressure, creat-
mg_zone I cond1t1ons in gravity-independent (uppermost) lung
regions. Positive-pressure mechanical ventilation may increase
alveolar pressure enough to convert some zone II regions to
z_on: I. This 1s one mechanism whereby positive pressure ven -
11lat1on mcreases alveolar dead space. Likewise, a Joss of blood
volume or massive vasodilation, as in septic shock, may decrease
~AP enough ~o create zone I conditions. Conversely, exercise
II_ onon_e II to zone III. The lung volume also affects regional
d1stnbut1on of blood flow, as implied in the earlier discussion
regarding the effect oflung volume on PVR (see Figure 6-7). At
total lung capacity when alveoli are maximally expanded, apical
regions are more likely to produce zone I conditions.
124 SECTION I The Respiratory System

Normal Matching of Ventilation
and Blood Flow
A_s d_iscussed in Chapter 3, tidal inspiration is preferentially
distributed to basal alveoli. This distribution occurs because
at FRC, the beginning point for a tidal inspiration, apical
3 the lung base has relatively more blood flow_th?n ventilation. As
alveoli are more distended and less compliant than basal alve-
oli. Although apical alveoli contain more volume at FRC, their
decreased compliance allows less volume change per breath and
less ventilation per minute. Similar to blood flow, ventilation is
least in the lung apex and greatest in the lung base. However, the
decrease in blood flow from base to apex is greater than the cor-
responding decrease in ventilation, which means that the lung
apex has relatively more ventilation than blood flow. Likewise,
a result, the ventilation-perfusion ratio (V/Q) increases from
the lung base to the lung apex (Figure 6-11).

q
2
Dead Space and Shunt Effects in the Normal Lung
V/Q Shunt refers to deoxygenated blood flowing through the capil-
laries of unventilated alveoli; dead space refers to the ventilation
of alveoli that have no capillary blood flow. Between these two
extremes are shuntlike and dead space-like effects, correspond-
ing with low and high V/Q ratios. Because the lun 9 apices have
relatively more ventilation than blood flow (high V/Q), a dead
space-like effect is produced. Likewise, because lung bases have
relatively less ventilation with respect to blood flow (low V/Q),
a shuntlike effect is produced. The overall average V/Q ratio in
the normal resting lung is abou t 0.8, which means ventilation
on average is slightly less than blood flow (Figure 6-12). During
exercise, the tremendous increase in ventilation causes the V/Q
ratio to increase. (Ventilation-perfusion relationships and their
effects on blood gases are discussed in Chapter 12.)

-{=_
Figure 6-11 Changes in blood flow, ventilation, and V/Q ratio in the
upright lung. From the lung base to the lung apex, blood flow decreases
more rapidly than ventilation. Consequently, the V/Q ratio increases
from the lung base to the lung apex. (Modified from West JB: Venti-
lation, blood flow and gas exchange, Oxford, 1965, Blackwell Science;
and Martin L: Pulmonary physiology in clinical practice, St Louis, 1987,
Mosby.)
Capillary Fluid Dynamics
Figure 6-13 illustrates hydrostatic and osmotic forces gov-
erning fluid m~vement across pulmonary capillary walls. The
pulmonary capillary acts as a semipermeable membrane, freely
p«meable to watec molecul~ but much 1~, permeable to 1.u-gec~

1.2

c 1.0
.E
;:: 0.8
0
-=
"O
0
0 0.6
Zi
0
C
0 0 .4

Q)
> 0 .2

0
0.1 0.5
5 10
Ventilation/perfusion ratio
. N al human V/Q curves. Overall average V/Q for the lung is slightly greaterthan O 8 h
F1gurdefl6- 12 Ii ohrtlmy exceeds ventilation. (From Berne RM, Levy MN: Physiology, ed 3, St Louis 19~3• aMs s b
own) by the thin vertical line. On average,
bloo ow s g • , os y.

molecules. The capillary endothelial membrane is relatively
impermeable to large high-molecular-weight proteins, although
the membrane's leakiness allows some proteins to enter the inter-
stitial space. Large protein molecules create osmotic pressure in
solution. The influence of proteins on the osmotic pressure of
blood plasma is called oncotic pressure. The greater the protein
concentration in blood plasma, the greater the oncotic pressure.
one can think of oncotic pressure as a force that "pulls" water
molecules from areas oflow oncotic pressure into areas of high
oncotic pressure. This is the opposite of hydrostatic pressure, a
force that "pushes" fluid from high to low pressures.
As shown in Figure 6-13, pulmonary capillary hydrostatic
blood pressure is about 7 mm Hg, and interstitial hydrostatic
fluid pressure is about 8 mm Hg. Interstitial fluid pressure
is "negative" because inward alveolar recoil and lymphatic
removal of fluid from this area create subatmospheric pressure.
The combined effect of interstitial and capillary hydrostatic
pressures is a force of 15 mm Hg, which tends to move fluid
out of the capillary. Adding to this force is an interstitial oncotic
pressure of about 14 mm Hg, which tends to pull fluid out of
the capillary into the interstitial space. Hydrostatic and oncotic
forces combine for a total of 29 mm Hg, favoring fluid move-
ment out of the capillary into the interstitial space. The only
force that moves fluid into the capillary is the blood's oncotic
pressure of about 28 mm Hg. The total force favoring fluid
movement out of the capillary is 29 mm Hg, whereas the total
force favoring inward movement is 28 mm Hg. This yields a net
3
mean filtration pressure of 1 mm Hg.
The following Starling equation describes fluid movement
4
across the capillary endothelium:
Clt =K1[(Pc - P;s) - a(irp1 -ir;.)]
Capillary
lnterstitium
HP + 7 HP-8
OP -28 OP-14
· 6-13 Fluid movement in pulmonary
Figure
and . fl 'dcapillaries.
f Lymphatic
· h vessels normally prevent fl ui'd accumulation
inward force refer to forces movmg m out o or mto t e pulmonary capillary. HP H d t .
frorn Guyton AC: Textbook of medical physiology, ed 8, Philadelphia, I 991, Saunders.) ' y fOS atlc pressure; OP, oncotic pressure. (Modified
125
CHAPTER 6 Pulmonary Blood Flow
In this equation, Qf represents the net flow_ of fluid (~L/
min) out of the capillary; Kf represents the ca?_1llary filtratt~n
coefficient, describing capillary fluid permeability characteris-
tics; p, represents capillary hydrostatic pressure; Pis r~presents
interstitial hydrostatic pressure; a represents the re~ect10n coef-
ficient, describing how easily the capillary endothelmm prevents
passage of solute particles (when a equals 1.0, the me~brane
is impermeable to solutes); l'tpi represents pla~ma oncot1c pres-
sure· and l't· represents interstitial fluid oncot1c pressure.
, IS f fl 'd
This filtration pressure causes a slight amount o U1 to
flow continuously from capillaries into interstitial spaces. The
lymphatic system, a natural sump for draining interstitial fluid,
immediately removes this fluid. Lymphatic action is extremely
important for preventing fluid leakage into alveoli; the alveolar
epithelium is so thin and weak that positive interstitial pressure
3
can rupture it, allowing fluid to flow into alveoli.
Pulmonary Edema
Pulmonary edema is the accumulation of fluid in the intersti-
tial spaces between capillaries and alveoli. Causes of pulmonary
edema include (I) increased hydrostatic pressure, (2) increased
capillary permeability, (3) decreased plasma oncotic pressure,
and (4) insufficient lymphatic drainage.
3
Increased Hydrostatic Pressure
If hydrostatic pressure in the pulmonary capillary increases
enough, fluid filtration into the interstitial space may exceed
lymphatic drainage, flooding the interstitial spaces. The
interstitial fluid volume cannot increase by much more than
100 mL before alveolar membranes rupture, causing alveolar
I Alveolus I
Outward force Inward force
HP 7 OP28
HP 8 Total in: 28 mm Hg
OP14
Total out: 29 mm Hg
Net filtration force
Out: 29 mm Hg
Total in: 28 mm Hg
Net out: 1 mm Hg
. m . th · ••
e mterst1t1um. Outward force
 126 SECTION I The Respiratory System
3
edema. Some fluid enters alveoli even in mild pulmonary
edema.
A common cause of hydrostatic pulmonary edema is left
ventricular failure. Coronary artery disease may reduce blood
I flow to the left ventricular muscle, reducing the effectiveness of
I
its pumping action. Blood dams up in the left atrium and pul-
monary veins, increasing pulmonary capillary pressures. This
type of edema is associated with a high PCWP and is called car-
diogenic pulmonary edema.
Mitra! valve stenosis, or narrowing of the mitral valve orifice,
also may cause blood to dam up in the pulmonary capillaries
and cause pulmonary edema. Overadministration of intrave-
nous fluids may create hypervolemia, or fluid overload, with
similar results.
Increased Capillary Permeability
Acute lung injuries that damage the alveolar capillary mem-
'
'' brane may increase its permeability to fluids and cause
pulmonary edema. This kind of edema is often called high-per-
meability pulmonary edema or noncardiac pulmonary edema.
Causes of alveolar capillary membrane injury include severe
infections such as pneumonia, endotoxins of sepsis, oxygen
toxicity, ARDS (regardless of the cause), and inhaled noxious
substances. Typically, patients with this kind of pulmonary
edema have normal pulmonary capillary pressure and left atrial
pressures (i.e., PCWP is generally normal) .
Decreased Plasma Oncotic Pressure
Capillary blood oncotic pressure is the only force favoring fluid
retention inside the capillary. If it is abnormally low, fluid easily
moves out of the capillary, overwhelming the removal capacity
of the lymphatic system (see Figure 6-13). Oncotic pulmonary
edema may be caused by protein starvation,* blood dilution as
'I a result of overadministration of intravenous fluids (hemodilu-
I ment); physical f indings (clinically significant hy-
tion), or certain renal diseases that allow urinary protein loss
I lI (proteinuria).
l Low oncotic pressure is rarely an isolated cause of pulmo-
nary edema. More likely, it is an aggravating factor in hydro-
static or high-permeability pulmonary edema.
lymphatic Insufficiency
Any condition that blocks or impedes pulmonary lymphatic
flow may cause fluid to accumulate in interstitial spaces. Lym-
phatic vessel compression by tumors is an example of such a
condition. Interstitial fibrotic diseases and conditions causing
interstitial scarring also may impede lymphatic drainage, caus-
ing pulmonary edema.
A normal lymphatic system responds to chronic, pathologi-
cally elevated capillary pressure by expanding and producing up
to a IO-fold increase in lymphatic drainage. 3 This response is a
large safety factor in chronic conditions that elevate pulmonary
• Proteins are the main source of blood oncotic pressure.
CLINICAL 6-6
FOCUS
Correlation of Pulmonary Capillary Wedge
Pressure with Hydrostatic Pulmonary Edema
Hydrostatic pulmonary edema is also known as cardiogenic
pulmonary edema (i .e. , arising from left heart failure). The inef-
ficient left ventricle causes blood to back up in the pulmonary
circulation, increasing hydrostatic pressure in the pulmonary
capillaries, increasing the pulmonary capillary wedge pressure
(PCWP). High capillary pressure forces fluid into the intersti-
tium and alveoli. Differentiating between cardiogenic and non-
cardiogenic pulmonary edema may be difficult because the
clinical presentation is similar in both . Clinical signs and symp-
toms of pulmonary edema (cardiogenic and noncardiogenic)
include dyspnea, wheezing, fine crackling breath sounds, and
hypoxemia. In cardiogenic pulmonary edema, the PCWP is
usually greater than 20 mm Hg. In contrast, PCWP is usu-
ally normal in noncardiogenic pulmonary edema . The cause of
pulmonary edema in this situation is often hyperpermeability,
or leakiness, of the alveolar capillary membrane. A general
, correlation between PCWP and clinical evidence of pulmo-
nary edema with normal capillary permeability follows .
PCWP Clinical Evidence of Hydrostatic Pulmonary
1 (mm Hg) Edema
1 16-18 No physical or x-ray findings evident
18-25 Some x-ray evidence of pulmonary edema
(engorged pulmonary vessels and appearance
of infiltrates) ; physical findings evident, including
some fine crackling breath sounds
>25
Obvious x-ray evidence of pulmonary edema
(greatly increased infiltrates and vascular engorge-
poxemia, tachypnea, respiratory distress, diffuse
crackles, and wheezing breath sounds)
hydrostatic blood pres h . .
. .. sure, sue as m1tral valve stenos1s. In
ch romc cond1t1ons c ill
H g wit.h ' ap ary pressures may reach 35 to 45 mm
out causing sig "fi
. m cant pu1monary edema whereas an
acute capillary pre · '
. . ssure mcrease to 20 mm Hg normally causes
s1gmficant edema 3 T bl . .
. · a e 6-1 summanzes the mechanisms
causmg pu1monary edema.
A patient with pu/m
ma/ plasma • . onary edema has normal PCWP and nor-
protein conce t ·
nism ofpu/m n ration. What is the likely mecha-
onary edema?
 ,..,

CHAPTER 6 Pulmonary Blood Flow 127

CLINICAL 6-7
FOCUS
Clinical Consequences and Treatment of Cardiogenic Pulmonary Edema
Cardiogen ic pulmonary edema engorges pu lmonary ca pil-
laries, fo rcing fluid into the interstitial spaces. Eventua lly,
this flu id may enter the alveoli, disrupting the alveolar sur-
factant system and causing alveolar collapse . Venti lation is
unevenly distributed throughout the lung because pul mo-
nary edema does not affect all alveolar units equa lly. Lung
compliance decreases because engorged capillaries sur-
round the alveol i, restrictin g their expansion. Alveolar col-
lapse also reduces lung compliance . As a result, the patient
develops hypoxemia and dyspnea. In life-threatening situa-
tions, fluid moves into the alveoli and airways, blocking ven-
tilation of alveoli.
The severity of pulmonary edema may vary. With evidence
of respiratory fa ilure, intubation and mechanical ventilation
are required. In all situations, treatment is focused on improv-
ing cardiac pumping effectiveness and maintaining adequate
oxygenation . Pharmacological agents commonly used to treat
cardiogenic pulmonary edema generally have one or more of
the fo llowing actions : (1) reduce blood volume, (2) increase
myocardia l contractility, and (3) decrease ca rdiac workloa d.
Diuretics decrease the circulating blood volume by increasing
urine output. Reducing th e blood volume tends to decrease
venous return, wh ich decreases pu lmonary vascu lar pres-
sures. Vasod ilators redistribute the blood volume by increas-
ing vessel diameters. This also reduces the venous return and
the pulmonary capi llary wedge pressure (PCWP). In addition,
vasodilators decrease the resistance against which the left
ventricle must pump, maki ng it a more effective pump. lnotro-
pic agents increase myocardial contractility and the heart rate,
improving left vent ricular fun ct ion. More blood is pumped out
of t he left at ri um, decreasing t he PCWP.
The goa ls in t reating cardiogenic pu lmonary edema are
to reverse pu lmonary capillary congestion, increase cardiac
pumping effectiveness, and improve oxygenation. In addition
to drugs, oxygen therapy plays an essential role in treating
pulmonary edema .

oxygenated blood entering the left atrium , wh ich causes

TABLE 6-1 PaO 2 normally to be lower than PA0 2 .
Mechanisms of Pulmona~ Ed,e~a - "· ~~-r·.' · e r - • The balloon-tipped, flow-d irected pulmonary artery catheter
measures right atrial , pulmonary artery, and pulmonary capil-
Factor Value Type Clinical Problem lary pressures; LAP is estimated from the PCWP.
Hydrostatic Increased Cardiac Left ventricular • PCWP obtained through the pulmonary artery catheter is
pressu re fai lure high in left ventricular pumping fa ilure because blood dams
Flu id overload up back to the capillaries behind the fail ing ventricle .
" Mitral stenosis • Factors affecting PVR are active or passive ; passive factors
Capillary Increased Noncardiac Sepsis include alveolar pressure, vascular pressure, and vascular
perme- Oxygen toxicity volume, and active factors involve smooth vascular muscle
Acute lung injury contraction or relaxation .
ability
Oncotic Decreased Noncardiac Protein • NO is a potent pulmonary vasodilator and is natura lly synthe-
pressure starvation sized by the vascular endothelial cells to help regulate PVR .
Hemodilution • HPV works to match blood flow with ventilation better, wh ich
Renal loss of helps moderate the severity of intrapulmonary shunting .
proteins • Acute lung injury causes release of inflammatory substances
Lymphatic Decreased Noncardiac Pu lmonary inter- that induce NO synthesis ; this tends to defeat HPV, w orsen-
drainage stitial fibrosis ing intrapulmonary shunt and decreasing the blood pressure .
• Inhaled vasodilators target well-ventilated lung reg ions, low-
ering their vascular resistance and diverting blood flow to
these regions ; this reduces shunting and arterial hypoxem ia.
• Gravity causes pulmonary blood flow to be categori zed into
POINTS TO REMEMBER three distinct zones of blood flow : zone I, no blood flow ;
• The pulmonary circulation is a low-pressure, low-resistance zone II, intermittent blood flow ; and zone Ill , continuou s
system ; the systemic circulation is a high-pressure, high- blood flow .
resistance system . . . . • Hypotension and high alveolar pressures can convert zone II
The pulmonary vasculature is highly d1stens1ble; arteries and regions to zone I.
veins are structurally similar and contain little smooth muscle • Ventilation and blood flow increase from the lung apex to the
compared with their systemic counterparts . . lung base .
• Some bronc h.1a I venous blood drains directly . into . pulmo-
h • The ventilation-to-blood flow ratio increases from lung ba se
.
nary veins, . d . deoxygenated blood direct1y into t e to lung apex.
intro uc1ng
 128 SECTION I The Respiratory System

. Jar effects of the nitric oxide syn-

• Pulmonary edema occurs when fluid filtration from capillar- 14. Watson D, et al: Ca rd10 vascu . • e hydrochloride (546C88) in
ies into the interstitial space overwhelms the removal capac- thase inhibitor NG-me thyl-L-aulrgm7a randomized, double-blind
ity of the lymphatic system . • 'th tic shock res ts O '
patients w1 sep .· tudy (study no. 144-002), Crit
• Pulmonary edema may be caused by high pressures, low placebo-controlled multlcenter s
2 2 4
plasma oncotic pressures, lymphatic insufficiency, or hyper- Care Med 32:28 : 00JE: Th pathophysiology of septic shock, Crit
15. Nduka 00, Pam11 o · e
permeability of the alveolar-capillary membrane.
Care Clin 25:677, 2~09. 1 fve iNOS inhibitor versus norepineph-
16. Su F, et al: Effects o a se ec i_ k 34·243, 2010.
References rine in the treatment of septic shock, Shoe . ·. .
17. Nae1Je.. R, Bnm10u
. . 11e S·· Physiology in med1cme:. . • importance
· I of
1. Jacobson JR, Garcia JGN: Pulmonary circulation and regulation of h . I ary vasoconstriction in mamtammg artena oxy-
fluid balance. In Mason RJ, et al: Murray and Nadel's textbook of ypo1?c pdu n:1°n te respiratory failure, Grit Care 5(2):67, 2001.
genatlon urmg acu •h AP d '
respiratory medicine, ed 5, Philadelphia, 20 l 0, Saunders. 18. Fishman AP: Pulmonary circulation. In _Fis man , e !tor:
2. Comroe JH: Physiology of respiration, ed 2, Chicago, 1974, Year Handbook of physiology, section 3: the _respiratory system, volume
Book Medical Publishers. I, circulation and nonrespiratory ftmctions, Bethesda, MD, 1985,
3. Hall JE: Guyton and Hall textbook of medical physiology, ed 12, American Physiological Society.
Philadelphia, 2011, Saunders.
19. Rudolph AM, Yuan S: Response of the pulmonary vasculature to
4. West JB: Respiratory physiology: the essentials, ed 8, Baltimore, hypoxia and H+ ion concentration changes, J Clm Invest45(3):399,
2008, Lippincott Williams & Wilkins.
1966.
5. Steendijk P: Going on and on with NO? (Editorial), Crit Care Med
20. Wagner PD, Powell FL, West JB: Ven tila tion , blood flow and gas -a-
(I 33(5):1157, 2005.
exchange. In Mason RJ, et al: Murray and N adel's textbook of respi-
ti 6. Furchgott RF: Endothelium-derived relaxing factor: discov-
ratory medicine, ed 5, Philadelphia, 201 0, Saunders.
ll ery, early studies, and identification as nitric oxide, Biosci Rep
19(4):235, 1999. 21. McCann UG, et al: Alveolar mechanics alter hypoxic pulmonary
ii vasoconstriction, Grit Care Med 30(6):1315, 2002.
7. Palmer RM, Ferrige AG, Moncada S: Nitric oxide release accounts
22. Ogasawara H, et al: Effects of selective nitric oxide synthase inhibi-
for the biological activity of endothelium-derived relaxing factor,
Nature 327(6122):524, 1987. tor on endotoxin-induced alteration in hypoxic pulmonary vaso-
8. Ignarro LJ, et al: Endothelium-derived relaxing factor produced constriction in sheep, J Cardiovasc Pharmacol 42( 4):521, 2003.
I
and released from artery and vein is nitric oxide, Proc Natl Acad 23. Carney D, DiRocco J, Nieman G: Dynamic alveolar mechanics and
-1 Sci US A 84(24):9265, 1987. ventilator-induced lung injury, Grit Care Med 33(Suppl 3):Sl22,
II 2005.
9. Altman LK: Three Americans awarded Nobel for discoveries of
II how a gas affects the body, The New York Times 309:Al4, October 24. Broccard AF, et al: Effects ofL-NAME and inhaled nitric oxide on
ii 13, 1998. ventilator-induced lung injury in isolated, perfused rabbit lungs,
Crit Care Med 32(9):2004, 1872.
ll 10. Reeves JT, Kinsella JP, Abman SH: Nitric oxide in treatment of
II persistent pulmonary hypertension of the newborn, Semin Resp 25. Ricard JD, Dreyfuss D, Saumon G: Ventilator-induced lung injury,
II Crit Care Med 15(6):495, 1994. Curr Opin Crit Care 8(1):12, 2002.
II 11. Anggard E: Nitric oxide: mediator, murderer, and medicine, Lan- 26. Lowson SM: Inhaled alternatives to nitric oxide, Grit Care Med
I cet 343(8907):1199, 1994. 33(3 Suppl):Sl88, 2005.
II 12. Lorente JA, et al: L-Arginine pathway in the sepsis syndrome, Crit 27. ~atto_uch K, et al: Inhaled prostacydin, nitric oxide, and nitroprus-
ll
Care Med 21(9):1287, 1993. s1de m pulmonary hyperte · ft ·
11
13. Enkhbaatar P, Traber DL: Pathophysiology of acute lung injury in J Card Surg20(2):171, 2005.ns1on a er m1tral valve replacement,
combined burn and smoke inhalation injury, Clin Sci 107(2):137, 28. Lee AJ, Chiao TB, Tsang MP· Sildenafil c ul h
2004. · Ann Pharmacother 39(5):86
s10n, · , _,or p monary yperten-
9 2005