MEDICINE (Dr.

Sobrepeña)

DISTURBANCES IN RESPI. FUNCTIONS

29 JANUARY 20178

DISTURBANCES OF RESPIRATORY FUNCTIONS MECHANICAL PROPERTIES OF EACH COMPONENT

Ö The primary functions of the respiratory system—to oxygenate Volume-Related Mechanical Properties—Statics

blood and eliminate carbon dioxide—require virtual contact between

blood and fresh air, which facilitates diffusion of respiratory gases
between blood and gas.
- This process occurs in the lung alveoli, where blood flowing
through alveolar wall capillaries is separated from alveolar gas
by an extremely thin membrane of flattened endothelial and
epithelial cells, across which respiratory gases diffuse and
equilibrate.
Ö Blood flow through the lung is unidirectional via a continuous
vascular path, along which venous blood absorbs oxygen from and
loses CO2 to inspired gas. z Elastic recoil pressure- a positive transmural pressure difference
Ö The path for airflow, in contrast, reaches a dead end at the alveolar between alveolar gas and its pleural surface to stay inflated
walls; thus the alveolar space must be ventilated tidally, with inflow
- Increases with increase in volume
of fresh gas and outflow of alveolar gas alternating periodically at - This is due to surface tension at the air-liquid interface
the respiratory rate (RR). between alveolar wall lining fluid and alveolar gas and to elastic
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Ö To provide an enormous alveolar surface area (typically 70 m ) for recoil of the lung tissue itself.
blood-gas diffusion within the modest volume of a thoracic cavity - Lung becomes stiff at high volumes and compliant at lower
(typically 7 L), nature has distributed both blood flow and ventilation volumes
among millions of tiny alveoli through multigenerational branching z At zero inflation pressure, even normal lungs retain some air in the
of both pulmonary arteries and bronchial airways. alveoli because the small peripheral airways are tethered open by
Ö As a consequence of variations in tube lengths and calibers along radially outward pull from inflated lung parenchyma attached to
these pathways as well as the effects of gravity, tidal pressure adventitia; as the lung deflates during exhalation, those small
fluctuations, and anatomic constraints from the chest wall, the
airways are pulled open progressively less, and eventually they
alveoli vary in their relative ventilations and perfusions. close, trapping some gas in the alveoli.
Ö For the lung to be most efficient in exchanging gas, the fresh gas z The elastic behavior of the passive chest wall
ventilation of a given alveolus must be matched to its perfusion. - chest wall encloses a large volume when pleural pressure equals
Ö For the respiratory system to succeed in oxygenating blood and body surface (atmospheric) pressure.
eliminating CO2, it must be able to ventilate the lung tidally and thus - chest wall is compliant at high enclosed volumes, readily
to freshen alveolar gas; it must provide for perfusion of the individual expanding even further in response to increases in transmural
alveolus in a manner proportional to its ventilation; and it must allow pressure.
adequate diffusion of respiratory gases between alveolar gas and - Chest wall remains compliant at small negative transmural
capillary blood pressures but as the volume enclosed by the chest wall
Ö Furthermore, it must accommodate severalfold increases in the
becomes quite small in response to large negative transmural
demand for oxygen uptake or CO2elimination imposed by metabolic pressures, the passive chest wall becomes stiff due to squeezing
needs or acid-base derangement. together of ribs and intercostal muscles, diaphragm stretch,
VENTILATION displacement of abdominal contents, and straining of ligaments
Three independently functioning components of the respiratory systems: and bony articulations.
1. the lung, including its airways; - Under normal circumstances, the lung and the passive chest
2. the neuromuscular system; and wall enclose essentially the same volume, the only difference
3. the chest walls, which include everything that is not lung or active being the volumes of the pleural fluid and of the lung
neuromuscular system parenchyma (both quite small).
§ mass of the respiratory muscles is part of the chest wall o the pressure required to displace the passive
§ the force these muscles generate is part of the neuromuscular respiratory system (lungs plus chest wall) at any
system volume is simply the sum of the elastic recoil
§ the abdomen (especially an obese abdomen) and the heart pressure of the lungs and the transmural pressure
(especially an enlarged heart) are, for these purposes, part of across the chest wall.
the chest wall

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 o This assumes a sigmoid shape, exhibiting stiffness at
high lung volumes (imparted by the lung), stiffness
at low lung volumes (imparted by the chest wall or
sometimes by airway closure), and compliance in the
middle range of lung volumes.
o The passive resting point of the respiratory system is
attained when alveolar gas pressure equals body
surface pressure
o At functional residual capacity, outward recoil of the
chest wall is balanced exactly by the inward recoil of
the lung
o When recoils are transmitted to the pleural fluid à
the lung is pulled both outward and inward z An important anatomic feature of the pulmonary airways is its
simultaneously at FRC, and thus its pressure falls treelike branching structure.
below atmospheric pressure (typically, –5 cmH2O). z An individual airways in each successive generation, from most
z The inspiratory muscles act on the chest wall to generate the proximal (trachea) to most distal (respiratory bronchioles), are
equivalent of positive pressure across the lungs and passive chest smaller than those of the parent generation, their number increases
wall, while the expiratory muscles generate the equivalent of exponentially such that the summed cross-sectional area of the
negative transrespiratory pressure. airways becomes very large toward the lung periphery.
- Variations in the maximal pressures variation is due to length- z Because flow (volume/time) is constant along the airway tree, the
tension relationships in striated muscle sarcomeres and to velocity of airflow (flow/summed cross-sectional area) is much
changes in mechanical advantage as the angles of insertion greater in the central airways than in the peripheral airways.
change with lung volume z During exhalation, gas leaving the alveoli must therefore gain
- airway closure always prevents the adult lung from emptying velocity as it proceeds toward the mouth. The energy required for
completely under normal circumstances this “convective” acceleration is drawn from the component of gas
z The excursion between full and minimal lung inflation is called vital energy manifested as its local pressure, which reduces intraluminal
capacity gas pressure, airway transmural pressure, airway size primarily
because of the dependence of lung recoil pressure on lung volume

Ö Example: In pulmonary fibrosis, lung recoil pressure is

Flow-Related Mechanical Properties—Dynamics increased at any lung volume, and thus the maximal expiratory
z The maintenance of airflow within the pulmonary airways requires a flow is elevated when considered in relation to lung volume.
pressure gradient that falls along the direction of flow, the Conversely, in emphysema, lung recoil pressure is reduced; this
magnitude of which is determined by the flow rate and the reduction is a principal mechanism by which maximal
frictional resistance to flow. expiratory flows fall. Diseases that narrow the airway lumen at
- At quiet tidal breathing, the pressure gradients driving any transmural pressure (e.g., asthma or chronic bronchitis) or
inspiratory or expiratory flow are small owing to the very low that cause excessive airway collapsibility (e.g., tracheomalacia)
frictional resistance of normal pulmonary airways (Raw, also reduce maximal expiratory flow.
normally <2 cmH2O/L per second). z Bernoulli effect
§ dynamic airflow limitation- a phenomenon that reduces the flow - It applies during inspiration; the more negative pleural
below which would have been expected if frictional resistance were pressures during inspiration lower the pressure outside of
the only impediment to flow during rapid exhalation. airways, thereby increasing transmural pressure and
o occurs because the bronchial airways through promoting airway expansion à inspiratory airflow limitation
which air is exhaled are collapsible rather than rigid seldom occurs due to diffuse pulmonary airway disease

The Work of Breathing

» The rate of ventilation is primarily set by the need to eliminate
carbon dioxide, and thus ventilation increases during exercise

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 (sometimes by more than twentyfold) and during metabolic » a dead space can be further increased functionally if some of
acidosis as a compensatory response. the inspired tidal volume is delivered to a part of the lung that
» the work rate required to overcome the elasticity of the receives no pulmonary blood flow and thus cannot contribute
respiratory system increases with both the depth and the to gas exchange (e.g., the portion of the lung distal to a large
frequency of tidal breaths, while the work required to overcome pulmonary embolus) à exhaled minute ventilation (VE = VT ×
the dynamic load increases with total ventilation. RR) includes a component of dead space ventilation (VD = VD ×
» A modest increase of ventilation is most efficiently achieved by RR) and a component of fresh gas alveolar ventilation (VA = [VT –
increasing tidal volume but not respiratory rate, which is the VD] × RR).
normal ventilatory response to lower-level exercise. » CO2 elimination from the alveoli is equal to VA times the
» At high levels of exercise, deep breathing persists, but difference in CO2 fraction between inspired air (essentially zero)
respiratory rate also increases. The pattern chosen by the and alveolar gas (typically ~5.6% after correction for
respiratory controller minimizes the work of breathing. humidification of inspired air, corresponding to 40 mmHg).
» The work of breathing also increases when disease reduces the » In the steady state, the alveolar fraction of CO2 is equal to
compliance of the respiratory system (occurs commonly in metabolic CO2 production divided by alveolar ventilation.
diseases of the lung parenchyma (interstitial processes or Because the alveolar and arterial CO2 tensions are equal, and
fibrosis, alveolar filling diseases such as pulmonary edema or because the respiratory controller normally strives to maintain
pneumonia, or substantial lung resection), or increases the arterial PCO2 (PaCO2) at ~40 mmHg, the adequacy of alveolar
resistance to airflow (in obstructive airway diseases such as ventilation is reflected in PaCO2.
asthma, chronic bronchitis, emphysema, and cystic fibrosis) » If the PaCO2 falls much below 40 mmHg, alveolar
» severe airflow obstruction can functionally reduce the hyperventilation is present; if the PaCO2 exceeds 40 mmHg, then
compliance of the respiratory system by leading to dynamic alveolar hypoventilation is present.
hyperinflation àexpiratory flows slowed by the obstructive » Ventilatory failure is characterized by extreme alveolar
airways disease may be insufficient to allow complete hypoventilation.
exhalation during the expiratory phase of tidal breathing; as a » As a consequence of oxygen uptake of alveolar gas into
result, the “functional residual capacity” from which the next capillary blood, alveolar oxygen tension falls below that of
breath is inhaled is greater than the static FRC inspired gas. The rate of oxygen uptake (determined by the
» With repetition of incomplete exhalations of each tidal breath, body’s metabolic oxygen consumption) is related to the
the operating FRC becomes dynamically elevated, sometimes to average rate of metabolic CO2 production, and their ratio—the
a level that approaches TLC. At these high lung volumes, the “respiratory quotient” (R = VCO2/VO2)—depends largely on the
respiratory system is much less compliant than at normal fuel being metabolized. For a typical American diet, R is
breathing volumes, and thus the elastic work of each tidal usually around 0.85, and more oxygen is absorbed than CO2 is
breath is also increased. The dynamic pulmonary hyperinflation excreted. Together, these phenomena allow the estimation of
that accompanies severe airflow obstruction causes patients to alveolar oxygen tension, according to the following
sense difficulty in inhaling—even though the root cause of this relationship, known as the alveolar gas equation:
pathophysiologic abnormality is expiratory airflow obstruction. PAO2 = FIO2 × (Pbar – PH2O) – PACO2/R
FIO2- inspired oxygen fraction
Adequacy of Ventilation Pbar -barometric pressure
» the respiratory control system that sets the rate of ventilation PH2O- vapor pressure of water (47 mmHg at 37°C) in
responds to chemical signals, including arterial CO2 and oxygen addition to alveolar ventilation (which sets PACO2) in
tensions and blood pH, and to volitional needs, such as the need determining PAO2.
to inhale deeply before playing a long phrase on the trumpet. An implication of the alveolar gas equation is that severe
» At the end of each tidal exhalation, the conducting airways are arterial hypoxemia rarely occurs as a pure consequence of
filled with alveolar gas that had not reached the mouth when alveolar hypoventilation at sea level while an individual is
expiratory flow stopped. During the ensuing inhalation, fresh breathing air. The potential for alveolar hypoventilation to
gas immediately enters the airway tree at the mouth, but the induce severe hypoxemia with otherwise normal lungs
gas first entering the alveoli at the start of inhalation is that increases as Pbar falls with increasing altitude.
same alveolar gas in the conducting airways that had just left GAS EXCHANGE
the alveoli. Diffusion
z Anatomic dead space (VD)- the volume of fresh gas does not enter » For oxygen to be delivered to the peripheral tissues, it must
the alveoli until the volume of the conducting airways has been pass from alveolar gas into alveolar capillary blood by diffusing
inspired. through alveolar membrane
» A quiet breathing with tidal volumes smaller than the anatomic » Diffusion through the alveolar membrane is so efficient
dead space introduces no fresh gas into the alveoli at all; only » the uptake of alveolar oxygen is ordinarily limited by the
that part of the inspired tidal volume (VT) that is greater than amount of blood transiting the alveolar capillaries rather than
the VD introduces fresh gas into the alveoli. by the rapidity with which oxygen can diffuse across the

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 membrane; consequently, oxygen uptake from the lung is said unventilated (shunt) lung regions; and, in unusual circumstances, by
to be “perfusion limited.” limitation of gas diffusion.
» oxygen and CO2 tensions in capillary blood leaving a normal PATHOPHYSIOLOGY
alveolus are essentially equal to those in alveolar gas
Ventilation/Perfusion Heterogeneity
» this is due to differential effects of gravity on lung mechanics
and blood flow throughout the lung and because of differences
in airway and vascular architecture among various respiratory
paths
» a V/Q heterogeneity can be particularly marked in disease
when;
(1) ventilation of unperfused lung distal to a pulmonary
embolus, in which ventilation of the physiologic dead space is
“wasted” in the sense that it does not contribute to gas
exchange; and
(2) perfusion of nonventilated lung (a “shunt”), which allows
venous blood to pass through the lung unaltered. Ventilatory Restriction Due to Increased Elastic Recoil—Example:
Idiopathic Pulmonary Fibrosis
ü raises lung recoil at all lung volumes, thereby lowering TLC,
FRC, and RV as well as forced vital capacity (FVC)
ü Maximal expiratory flows are also reduced from normal values
but are elevated when considered in relation to lung volumes
ü Increased flow occurs both because the increased lung recoil
drives greater maximal flow at any lung volume and because
airway diameters are relatively increased due to greater radially
outward traction exerted on bronchi by the stiff lung
parenchyma
ü airway resistance is also normal.
ü Destruction of the pulmonary capillaries by the fibrotic process
results in a marked reduction in diffusing capacity
ü Oxygenation is often severely reduced by persistent perfusion
of alveolar units that are relatively underventilated due to
fibrosis of nearby (and mechanically linked) lung.

z The resulting arterial hypoxemia is refractory to supplemental Ventilatory Restriction Due to Chest Wall Abnormality—Example:
inspired oxygen. The reason is that Moderate Obesity
1. raising the inspired FIO2 has no effect on alveolar gas tensions ü the outward recoil of the chest wall is blunted by the weight of
in nonventilated alveoli and; chest wall fat and the space occupied by intraabdominal fat
2. while raising inspired FIO2 does increase PACO2 in ventilated ü preserved inward recoil of the lung overbalances the reduced
alveoli, the oxygen content of blood exiting ventilated units outward recoil of the chest wall, and FRC falls.
increases only slightly, as hemoglobin will already have been ü a respiratory muscle strength and lung recoil remain normal,
nearly fully saturated and the solubility of oxygen in plasma is TLC is typically unchanged and RV is normal.
quite small. ü Mild hypoxemia may be present due to perfusion of alveolar
z Perfusion of relatively underventilated alveoli results in the units that are poorly ventilated
incomplete oxygenation of exiting blood. ü Flows remain normal, as does the diffusion capacity of the lung
z When mixed with well-oxygenated blood leaving higher V/Q regions, for carbon monoxide (DLCO)
this partially reoxygenated blood disproportionately lowers arterial
PaO2, although to a lesser extent than does a similar perfusion Ventilatory Restriction Due to Reduced Muscle Strength—Example:
fraction of blood leaving regions of pure shunt. In addition, in Myasthenia Gravis
contrast to shunt regions, inhalation of supplemental oxygen does ü FRC remains normal, as both lung recoil and passive chest wall
raise the PAO2, even in relatively underventilated low V/Q regions, recoil are normal
and so the arterial hypoxemia induced by V/Q heterogeneity is ü TLC is low and RV is elevated because respiratory muscle
typically responsive to oxygen therapy strength is insufficient to push the passive respiratory system
z In sum, arterial hypoxemia can be caused by substantial reduction of fully toward either volume extreme.
inspired oxygen tension; by severe alveolar hypoventilation; by ü low TLC and the elevated RV, FVC and FEV1 are reduced as
perfusion of relatively underventilated (low V/Q) or completely “innocent bystanders.”
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 ü airway size and lung vasculature are unaffected, both Raw and volume of gas being compressed. The patient sits in
DLCO are normal a body plethysmograph (a chamber usually made of
ü Oxygenation is normal unless weakness becomes so severe that transparent plastic to minimize claustrophobia) and,
the patient has insufficient strength to reopen collapsed alveoli at the end of a normal tidal breath (i.e., when lung
during sighs, with resulting atelectasis. volume is at FRC), is instructed to pant against a
closed shutter, thus periodically compressing air
Airflow Obstruction Due to Decreased Airway Diameter—Example: Acute within the lung slightly.
Asthma o Once FRC is obtained, TLC and RV are calculated by
ü “Scooping” of the flow-volume loop is caused by reduction of adding the value for inspiratory capacity and
airflow, especially at lower lung volumes subtracting the value for expiratory reserve volume
ü TLC usually remains normal but FRC may be dynamically o The most important determinants of healthy
elevated. individuals’ lung volumes are height, age, and sex,
ü RV is increased à reduces FVC. but there is considerable additional normal variation
ü Because central airways are narrowed, Raw is usually elevated. beyond that accounted for by these parameters,
ü Mild arterial hypoxemia is often present due to perfusion of race influences lung volumes.
relatively underventilated alveoli distal to obstructed airways AIR FLOW
but DLCO is normal or mildly elevated. » During an FVC maneuver, the patient inhales to TLC and then
exhales rapidly and forcefully to RV; this method ensures that
Airflow Obstruction Due to Decreased Elastic Recoil—Example: Severe flow limitation has been achieved, so that the precise effort
Emphysema made has little influence on actual flow.
ü elevated TLC is the hallmark » The total amount of air exhaled is the FVC, and the amount of
ü FRC is more severely elevated due both to loss of lung elastic air exhaled in the first second is the FEV1; the FEV1 is a flow rate,
recoil and to dynamic hyperinflation revealing volume change per time.
ü Residual volume is very severely elevated because of airway » FEV1/FVC ratio is typically reduced in airflow obstruction, this
closure and because exhalation toward RV may take so long condition can also reduce FVC by raising RV, sometimes
ü Both FVC (because of the severe elevation of RV) and rendering the FEV1/FVC ratio “artifactually normal” with the
FEV1 (because loss of lung elastic recoil reduces the pressure erroneous implication that airflow obstruction is absent. To
driving maximal expiratory flow and also reduces tethering circumvent this problem, it is useful to compare FEV1 as a
open of small intrapulmonary airways) are markedly decreased fraction of its predicted value with TLC as a fraction of its
ü Central airways are normalà Raw is normal in “pure” predicted value.
emphysema » The relationships among volume, flow, and time during
ü Loss of alveolar surface and capillaries in the alveolar walls spirometry are best displayed in two plots—the spirogram
reduces DLCO (volume vs. time) and the flow-volume loop (flow vs. volume)
ü arterial hypoxemia usually is not seen at rest until emphysema
becomes very severe AIRWAYS RESISTANCE
» total resistance of the pulmonary and upper airways is
FUNCTIONAL MEASUREMENTS measured in the same body plethysmograph used to measure
Measurement of Ventilatory Function FR
LUNG VOLUMES » patient is asked once again to pant, but this time against a
» in a slow vital capacity maneuver, the subject inhales from FRC, closed and then opened shutter. Panting against the closed
fully inflating the lungs to TLC, and then exhales slowly to RV shutter reveals the thoracic gas volume
» VC- the difference between TLC and RV, represents the maximal » Simultaneous measurement of flow allows the calculation of
excursion of the respiratory system lung resistance (as flow divided by pressure).
» To determine absolute lung volumes, two approaches are » In health, Raw is very low (<2 cmH2O/L per second), and half of
commonly used: the detected resistance resides within the upper airway.
a. inert gas dilution » In the lung, most resistance originates in the central airways.
o a known amount of a nonabsorbable inert gas For this reason, airways resistance measurement tends to be
(usually helium or neon) is inhaled in a single large insensitive to peripheral airflow obstruction.
breath or is rebreathed from a closed circuit; the
inert gas is diluted by the gas resident in the lung at RESPIRATORY MUSCLE STRENGTH
the time of inhalation, and its final concentration » patient is instructed to exhale or inhale with maximal effort
reveals the volume of resident gas contributing to against a closed shutter while pressure is monitored at the
the dilution. mouth.
b. body plethysmography » Pressures greater than ±60 cmH2O at FRC are considered
o FRC is determined by measuring the compressibility adequate and make it unlikely that respiratory muscle
of gas within the chest, which is proportional to the

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 weakness accounts for any other resting ventilatory
dysfunction that is identified.
Measurement of Gas Exchange
DIFFUSING CAPACITY (DLCO)
» This test uses a small (and safe) amount of carbon monoxide
(CO) to measure gas exchange across the alveolar membrane
during a 10-sec breath hold.
» CO in exhaled breath is analyzed to determine the quantity of
CO crossing the alveolar membrane and combining with
hemoglobin in red blood cells.
» This “single-breath diffusing capacity” (DLCO) value increases
with the surface area available for diffusion and the amount of
hemoglobin within the capillaries, and it varies inversely with
alveolar membrane thickness.
» Thus, DLCO decreases in diseases that thicken or destroy alveolar
membranes (e.g., pulmonary fibrosis, emphysema), curtail the
pulmonary vasculature (e.g., pulmonary hypertension), or
reduce alveolar capillary hemoglobin (e.g., anemia).
» Single-breath diffusing capacity may be elevated in acute
congestive heart failure, asthma, polycythemia, and pulmonary
hemorrhage.

ARTERIAL BLOOD GASES

» The effectiveness of gas exchange can be assessed by
measuring the partial pressures of oxygen and CO2 in a
sample of blood obtained by arterial puncture.
» The oxygen content of blood (CaO2) depends upon arterial
saturation (%O2Sat), which is set by PaO2, pH, and
PaCO2 according to the oxyhemoglobin dissociation curve.
CaO2 can also be measured by oximetry:
CaO2 (mL/dL) = 1.39 (mL/dL) × [hemoglobin](g) × % O2 Sat
+ 0.003 (mL/dL/mmHg) × PaO2 (mmHg)
» If hemoglobin saturation alone needs to be determined, this
task can be accomplished noninvasively with pulse oxymetry.