Flashcards in Five Deck (12):
Define RFC as it pertains to elastic recoil forces and chest wall forces.
Thus, lung volume at
end-expiration and with the glottis open to atmospheric pressure
represents the balance point of these directionally opposite
forces, and was defi ned previously as functional residual
Define pneumothorax, atelectasis, and static compliance.
The description in Chap. 4 of gas movement during ventilation
introduced the concept of static elastic and surface tension
recoil forces. These forces are visually evident on excised
healthy lungs that quickly collapse to their minimal volume
if the chest is opened to outside air, creating a pneumothorax.
Such lungs normally retain air only in large airways and
a few clusters of alveoli, having undergone atelectasis. The
collapsed lungs are suspended by the trachea within a vacuum
jar that can be evacuated to simulate negative intrapleural
pressure (PIP) in vivo (Fig. 5.1). As jar pressure is made more
negative in small stable increments, the lungs ‘inspire’ air
and equilibrate at a new volume until jar pressure is altered
again. In this stepwise way, stable changes in total lung volume
per unit change in pressure are recorded when dynamic
airway resistance is absent, and used to calculate their static
Describe what happens when a negative pressure is applied to a lung in vitro. What is PCO? When is static compliance maximal during inflation? Deflation? What is hysteresis and what does it mean in this particular experiment?
When negative pressure is fi rst applied to the collapsed
lungs, their volume does not change, that is, their compliance is zero. Then, as the lungs achieve a critical opening pressure (PCO) their compliance rapidly increases and the lungs fi ll easily. Thus, PCO is the minimal pressure required to open or recruit alveoli and small airways that were previously atelectatic. As pressure inside the jar becomes even
more negative (−20 to −30 cm H2O), lung volume approaches
a maximum, equivalent to total lung capacity TLC in vivo.
Then, as the vacuum is slowly released stepwise toward 0 cm
H2O, normal lungs defl ate toward residual volume RV. A
complete cycle of fi lling and emptying the lungs shows that
their static compliance (ΔV/ΔP) is maximal when lung volume
= 50%-70% of total lung capacity during infl ation versus
20%-30% of total lung capacity during defl ation.
Furthermore, a more negative pressure is needed to infl ate lungs to a volumethan to maintain that volume during the next defl ation. This discrepancy
between infl ation and defl ation is termed hysteresis,
with an enclosed area that is proportional to the non-recoverable work required during infl ation to overcome the recoil properties of air-fi lled lungs.
What differences exist when filling the in vitro lung (connected to negative pressure) with saline instead of air? what does this mean concerning the cause of hysteresis in static lung recoil?
What component of static lung recoil causes hysteresis?
The answer can be found by repeating the stepwise infl ation
and defl ation of excised lungs with normal saline, NS
(0.9% NaCl) instead of air to fi ll the airways (Fig. 5.2). Doing
so yields a similar but not identical pair of curves to those
in Fig. 5.1. The fi rst and most obvious difference in compliance ΔV/ΔP between saline-fi lled lungs and air-fi lled organ is that less negative pressure is required to achieve both PCO and then TLC, in this example being only −8 cm H2O for total lung capacity with saline versus −20 cm H2O for air. Indeed, a PCO cannot really be demonstrated for saline-fi lled lungs.
Second, regardless of where static compliance is measured during infl ation and defl ation, it is always greater for saline filled lungs than for air-fi lled lungs, that is, the saline ΔV/ΔP curves are steeper. A third difference is the negligible hysteresis in saline-fi lled lungs. Energetically this means that virtually
all ventilatory effort expended to infl ate them is recovered
during defl ation, since saline-fi lled lungs behave more like an
ideal elastic model.
This means that the hysteresis is caused simply by the surface tension recoil forces. The saline filled lungs don't have to overcome these, only the elastic recoil. Therefore, they don't exhibit hysteresis.
What happens in the saline-lavaged lungs in this in vitro lung experiment? What outcomes does this make more likelly?
When these saline-lavaged lungs are reinfl ated to mimic
the original air-fi lled ΔV/ΔP curves (Fig. 5.2), they are now much less compliant than before lavage, or ‘stiffer’ in the jargon
of pulmonary medicine. As a result, a more negative PIP must
be applied to achieve both PCO and total lung capacity, which
will require more ventilatory effort. Equally signifi cant, lavaged
lungs show more hysteresis refl ecting the non-recoverable work
of breathing. Ventilating such lungs increases the risks of pleural rupture and respiratory muscle fatigue due to the high infl ating pressures needed to achieve total lung capacity.
What is the law of laplace? How does this apply to surface tension recoil forces
Second, the greater pressure and
energy needed to infl ate air-fi lled lungs represent the additional
effort to overcome surface tension recoil forces that
exist at the interface between alveolar air and the thin layer of
fl uid that covers the moist epithelial surfaces, and that attempt
to make small air bubbles like the alveoli even smaller. Surface
tension recoil forces can be described by the law of Laplace
(Fig. 5.3), which states that:
Infl ating pressure = (2 ·T)/r
where T = surface tension of the fl uid, and r = radius of a
This mathematical relationship predicts that when two
adjacent alveoli with the same radii are connected by a common
airway, any perturbation that causes either alveolus to
become even slightly smaller than its neighbor will initiate
the spontaneous collapse of the slightly smaller alveolus into
the slightly larger one. The resulting larger alveolus is then
more stable than either alveolus was before, since a lower pressure is required to keep the larger one open than was needed for either of the smaller ones.
What is pulmonary surfactant? What is it made out of? When does it work best? When does it do the least work? What are its two major benefits? How does it accomplish them?
The role of pulmonary surfactant is evident when comparing
air-fi lled compliance curves of fresh and lavaged lungs
(Fig. 5.2). This secreted product of type 2 epithelial cells
contains several glycerol-backbone phospholipids, primarily
dipalmitoyl phosphatidylcholine (DPPC) or lecithin, and
four associated apoproteins (Table 5.1; Fig. 5.4). Due to the
amphipathic properties of phospholipids in an aqueous medium
like the alveolar lining fl uid, they preferentially orient at the
alveolar air-fl uid interface and suppress surface tension in a
concentration-dependent manner (Fig. 5.3). The surface density
of the phospholipids, and thus their surface tension-reducing
ability, is highest at low alveolar volumes near the end of expiration
when alveoli are most unstable due to their smaller radii
(Fig. 5.3). Conversely, the surface density of DPPC molecules,
and thus their surface tension-reducing ability, is lowest when
alveoli are maximally expanded during inspiration, and thus
are most stable. In this manner, DPPC permits large changes
in alveolar volume with small changes in distending pressure,
and stabilizes adjacent alveoli of potentially very different radii.
An additional benefi t of surfactant is that the reduced surface
tension at the air-fl uid interface retards the movement of capillary
ultrafi ltrate through the septal interstitium and into alveolar
airspaces. With insuffi cient surfactant, surface tension at the
alveolar air-fl uid interface accentuates hydrostatic pressure gradients
between the capillary lumen and the interstitium. With
functional surfactant present, the alveoli stay drier.
Describe primary and secondary surfactant deficiency. Describe the immediate results of either.
Consider again the air V/P curves for post-lavage lungs
(Fig. 5.2), where PCO and hysteresis are greater because
secreted pulmonary surfactant is absent or inactivated. Once
open, surfactant-defi cient alveoli are less compliant and may
not infl ate to total lung capacity. During defl ation, surfactantdefi
cient alveoli also are less stable at low lung volumes. Primary
surfactant defi ciency due to pulmonary immaturity is
the essential pathology of the neonatal respiratory distress
syndrome (neonatal RDS), a leading cause of perinatal mortality
in developed countries. Neonatal RDS will be discussed
in greater detail (Chap. 39). Secondary surfactant defi ciency
occurs when previously healthy lungs fi ll with edema fl uid that
inactivates or interferes with the function of surfactant already
in the alveoli. Such acute lung injury (ALI) is an important
feature of the acute respiratory distress syndrome (ARDS),
which is the subject of Chap. 28.
What are collectins? What are their roles? What does deficiency of them lead to?
The surfactant proteins (SP) A, B, C, and D were originally
presumed to serve primarily as chaperones to facilitate
processing, intracellular storage, and/or secretion of
surfactant phospholipids. Now considered members of
the Collectin superfamily of proteins, SP-A and SP-D in
particular have important antimicrobial properties within
the alveoli and distal airways, where they aggregate
specifi c classes of bacteria and their endotoxins or
exotoxins (Chap. 10). Thus, inherited or acquired
defi ciencies in the SP proteins can cause secretory defects
of surfactant and/or enhanced susceptibility to inhaled
pathogens or their byproducts.
When does surfactant begin to be made and how? How is this synth. seen histologically? How can it be measured? Why is it important to measure surfactant production? What are the two different measures that are used?
As described in Chap. 2, lungs are usually the last fetal organ
to mature suffi ciently to support extrauterine life. During a
normal pregnancy, synthesis of pulmonary surfactant begins
within maturing alveolar type 2 epithelial cells by 32-34 weeks
gestation (Fig. 5.5). Its synthesis is associated with enhanced
collectin gene expression, and is evident by electron microscopy
as an increased volume density of surfactant-containing
lamellar bodies (LB) in type 2 cells. Because these lamellar
bodies are shed by exocytosis, their phospholipids become
measurable in the amniotic fl uid as it moves rhythmically in
and out of the oropharynx and immature lungs of the fetus.
Not surprisingly, neonatal RDS is most common among
infants born prematurely, in whom inadequate production
of pulmonary surfactant will result in excessive surface tension
recoil, noncompliant lungs, and exceptionally high values for PCO. Thus, when a preterm delivery is anticipated or
unavoidable, it is important to assess the quality and quantity
of fetal lung surfactant to guide appropriate obstetrical management.
Given amniotic fl uid’s exposure to fetal lung secretions,
it is a highly suitable laboratory specimen for assessing
intrauterine production of pulmonary surfactant.
The most common laboratory index of surfactant in amniotic
fl uid is its abundance of DPPC or lecithin versus its sphingomyelin,
the historically important L/S ratio, since amniotic
levels of sphingomyelin remain fairly constant throughout gestation.
Increasingly, neonatologists may also assess the ratio
of amniotic phosphatidylglycerol to sphingomyelin, since the
phosphatidylglycerol tends to peak after the rising L/S.
What are the physical ways in which surfactant in amniotic fluid is measured? What are the normal values? What are the pros and cons of each?
When surfactant is present in suffi cient concentration, the
amniotic fl uid will form a highly stable surface fi lm that supports
a durable foam of bubbles. Adding increasing amounts
of an organic solvent like ethanol to a predetermined volume
of amniotic fl uid reduces the stability of this bubble foam.
Thus, the highest fractional volume of ethanol that still supports
bubbles in a sample is its foam stability index (FSI), with
an FSI >0.47 interpreted as mature. Although labor-intensive,
the test is sensitive and specifi c.
Lamellar bodies from type 2 cells are three-dimensional
aggregates that scatter light and produce a haziness or turbidity
when suspended in amniotic fl uid. These particles can
be counted directly on a sample of amniotic fl uid using the
platelet channel of most automated hematology analyzers. A
lamellar body count ≥35,000/μL is usually considered indicative
of adequate lung maturity, but is affected by the type of
instrument used. Thus the test is considered rapid and sensitive,
but not very specifi c.
A number of fl uorescent dyes will partition between albumin
in the aqueous phase of amniotic fl uid and the surfactant
aggregates within that fl uid. In such assays, the degree of light
polarization is high in the aqueous phase and low in the surfactant
phase due to the short half life of fl uorescence in aqueous
phase relative to rotational diffusion. The amount of fl uorescence
polarization (FP) in an amniotic fl uid is compared
against standard curves constructed using purifi ed albumin and
surfactant. Results are reported as mg surfactant/g albumin,
with a value of FP >55 mg/g albumin considered mature.