Disturbances in Respiratory Function

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The primary functions of the respiratory system— —require virtual contact between blood and fresh air, which facilitates diffusion of respiratory gases between blood and gas. -

This process occurs in the

, 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. !

Blood flow through the lung is

  via a continuous

vascular path, along which venous blood absorbs oxygen from and loses CO2 to inspired gas. !

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The path for airflow, in contrast, reaches a dead end at the

- a positive transmural pressure difference between alveolar gas and its pleural surface to stay inflated

; 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

To provide an enormous alveolar surface area

 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

 nature has distributed both blood flow and ventilation

among millions of tiny alveoli through multigenerational branching

volumes #

of both pulmonary arteries and bronchial airways. !

alveoli because the small peripheral airways are tethered open by

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,

adventitia; as the lung deflates during exhalation, those small , the

airways are pulled open progressively less, and eventually they

alveoli vary in their relative ventilations and perfusions. !

For the lung to be most efficient in exchanging gas, the fresh gas ventilation of a given alveolus must be matched to its perfusion.

!

At zero inflation pressure, even normal lungs retain some air in the

close, trapping some gas in the alveoli. #

-

chest wall encloses a

-

chest wall is compliant at

For the respiratory system to succeed in oxygenating blood and eliminating CO 2, it must be able to ventilate the lung tidally and thus to freshen alveolar gas; it must provide for perfusion of the in dividual

expanding even further in response to increases in transmural

alveolus in a manner proportional to its ventilation; and it must allow adequate diffusion of respiratory gases between alveolar gas and

pressure. -

capillary blood !

, readily

Chest wall remains compliant at small negative transmural pressures but as the volume enclosed by the chest wall

Furthermore, it must accommodate severalfold increases in the

becomes quite small in response to large negative transmural

demand for oxygen uptake or CO 2elimination 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, displacement of abdominal contents, and straining of li gaments

Three independently functioning components of the respiratory systems : 1.

the

2.

the

3.

the

, including its airways;

and bony articulations. -

Under normal circumstances, the

; and , which include everything that is not lung or active

neuromuscular system "

mass of the respiratory muscles is part of the

"

the force these muscles generate is part of the

, the only difference being the volumes of the pleural fluid and of the lung parenchyma (both quite small). o

the pressure required to displace the passive respiratory system (lungs plus chest wall) at any 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

1

o

This assumes a sigmoid shape, exhibiting  (imparted by the lung), (imparted by the chest wall or sometimes by airway closure), and

o

The passive resting point of the respiratory system is attained when

o

At functional residual capacity,

o

When recoils are transmitted to the pleural fluid $ the lung is pulled both outward and inward

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An important anatomic feature of the pulmonary airways is its .

simultaneously at FRC, and thus its pressure falls below atmospheric pressure (typically, #

The

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An individual airways in each successive generation, from most proximal (trachea) to most distal (respiratory bronchioles), are

  act on the chest wall to

, their number increases

s and passive chest

  such that the summed cross-sectional area of the

wall, while the

airways becomes very large toward the lung periphery. -

Variations in the maximal pressures variation is due to

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Because flow (volume/time) is constant along the airway tree, the velocity of airflow (flow/summed cross-sectional area) is much

  in striated muscle sarcomeres and to

 than in the peripheral airways.

  as the angles of insertion #

change with lung volume #

During

, 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 energy manifested as its local pressure, which reduces intraluminal

The excursion between full and minimal lung inflation is called

gas pressure, airway transmural pressure, airway size primarily because of the dependence of lung recoil pressure on lung volume

!

Example:

, lung recoil pressure is

increased at any lung volume, and thus the maximal expiratory #

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

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

, the pressure gradients driving

inspiratory or expiratory flow are

any transmural pressure (e.g., asthma or chronic bronchitis) or

 owing to the very low

that cause excessive airway collapsibility (e.g., tracheomalacia)

frictional resistance of normal pulmonary airways (R aw , normally "

).

, lung recoil pressure is reduced; this

also reduce maximal expiratory flow. #

- 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,

o

thereby

increasing

transmural

pressure

and

occurs because the bronchial airways through

promoting airway expansion $  inspiratory airflow limitation

which air is exhaled are

seldom occurs due to diffuse pulmonary airway disease

 rather than rigid

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

2

(sometimes by more than twentyfold) and during

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a dead space

 as a compensatory response. »

the work rate required to overcome the elasticity of the

 and thus cannot contribute

respiratory system increases with both the

to gas exchange (e.g., the portion of the lung distal to a large pulmonary embolus) $ exhaled minute ventilation (V E = V T

!

the dynamic load increases with total ventilation.

RR) includes a component of dead space ventilation (V D = V D

!

A modest increase of ventilation is

RR) and a component of fresh gas alveolar ventilation (V A = [VT –

, while the work required to overcome

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, which is the normal ventilatory response to lower-level exercise. »

»

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CO2 elimination from the alveoli is equal to V A  times the

At high levels of exercise, deep breathing persists, but

difference in CO 2 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

 when disease reduces the

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In the steady state, the alveolar fraction of CO 2  is equal to

compliance of the respiratory system ( occurs commonly in

metabolic CO 2  production divided by alveolar ventilation.

diseases of the lung parenchyma (interstitial processes or

Because the alveolar and arterial CO 2 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 Pa CO2 .

asthma, chronic bronchitis, emphysema, and cystic fibrosis)  »

VD] ! RR).

»

If

the

Pa CO2   falls

much

below

40

mmHg,

alveolar

severe airflow obstruction can functionally reduce the

hyperventilation is present; if the Pa CO2  exceeds 40 mmHg, then

compliance of the respiratory system by leading to dynamic

alveolar hypoventilation is present.

hyperinflation $expiratory flows slowed by the obstructive

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Ventilatory failure is characterized by

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As a consequence of oxygen uptake of alveolar gas into

airways disease may be insufficient to allow complete exhalation during the expiratory phase of tidal breathing; as a

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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 CO 2 production, and their ratio—the

a level that approaches TLC. At these high lung volumes, the

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 CO 2 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

pathophysiologic abnormality is expiratory airflow obstruction.

:

PAO2  = FIO2 ! (Pbar  – PH2 O) – P ACO2/R FIO2 - inspired oxygen fraction Pbar  -barometric pressure

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the respiratory control system that sets the rate of ventilation

PH2 O- vapor pressure of water (47 mmHg at 37°C) in

responds to chemical signals, including arterial CO 2  and oxygen

addition to alveolar ventilation (which sets P ACO2) 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 the alveoli. #

(VD)- the volume of fresh gas

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For oxygen to be delivered to the peripheral tissues, it must

until the volume of the conducting airways has been

 by diffusing

inspired. »

through alveolar membrane

A quiet breathing with  into the alveoli at all; only that part of the inspired tidal volume (V T) that is greater than the VD introduces fresh gas into the alveoli.

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Diffusion through the alveolar membrane is so efficient

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the uptake of alveolar oxygen is ordinarily  rather than 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 “

limitation of gas diffusion.

.”

oxygen and CO 2  tensions in capillary blood leaving a normal alveolus are essentially equal to those in alveolar gas

»

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

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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.

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raises lung recoil at all lung volumes, thereby lowering TLC, FRC, and RV as well as forced vital capacity (FVC)

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Maximal expiratory flows are also reduced from normal values but are elevated when considered in relation to lung volumes

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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

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airway resistance is also normal.

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Destruction of the pulmonary capillaries by the fibrotic process results in a marked reduction in diffusing capacity

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Oxygenation is often severely reduced by persistent perfusion of alveolar units that are relatively underventilated due to fibrosis of nearby (and mechanically linked) lung.

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The resulting

is refractory to supplemental

inspired oxygen. The reason is that 1.

raising the inspired F IO2  has no effect on alveolar gas tensions

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in nonventilated alveoli and; 2.

while raising inspired FI O2   does increase PA CO2   in ventilated

chest wall fat and the space occupied by intraabdominal fat %

alveoli, the oxygen content of blood exiting ventilated units increases only slightly, as hemoglobin will already have been

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%

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a respiratory muscle strength and lung recoil remain normal, TLC is typically unchanged and RV is normal.

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Perfusion of relatively underventilated alveoli results in the incomplete oxygenation of exiting blood.

preserved inward recoil of the lung overbalances the reduced outward recoil of the chest wall, and FRC falls.

nearly fully saturated and the solubility of oxygen in plasma is quite small.

the outward recoil of the chest wall is blunted by the weight of

Mild hypoxemia may be present due to perfusion of alveolar units that are poorly ventilated

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When mixed with well-oxygenated blood leaving higher V/Q regions,

Flows remain normal, as does the diffusion cap acity of the lung for carbon monoxide (D LCO )

this partially reoxygenated blood disproportionately lowers arterial Pa O2 , although to a lesser extent than does a similar perfusion fraction of blood leaving regions of pure shunt. In addition, in contrast to shunt regions, inhalation of supplemental oxygen does

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raise the PA O2 , even in relatively underventilated low V/Q regions, and so the arterial hypoxemia induced by V/Q heterogeneity is

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perfusion of relatively underventilated (low V/Q) or completely

  because respiratory muscle strength is insufficient to push the passive respiratory system

In sum, arterial hypoxemia can be caused by substantial reduction of inspired oxygen tension; by severe alveolar hypoventilation; by

, as both lung recoil and passive chest wall

recoil are normal

typically responsive to oxygen therapy #

 remains

fully toward either volume extreme. %

low TLC and the elevated RV, FVC and FEV 1  are reduced as “innocent bystanders .”

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%

airway size and lung vasculature are unaffected, both R aw  and

volume of gas being compressed. The patient sits in

DLCO  are normal

a body plethysmograph (a chamber usually made of

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l 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 within the lung slightly. Once FRC is obtained, TLC and RV are calculated by

o

%

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“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

TLC usually remains normal but FRC may be dynamically

The

o

most

important

determinants

of

healthy

elevated.

individuals’ lung volumes are

,

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RV is increased $ reduces FVC.

but there is considerable additional normal variation

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Because central airways are narrowed, R aw  is usually elevated.

beyond that accounted for by these parameters,

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Mild arterial hypoxemia is often present due to perfusion of

race influences lung volumes.

relatively underventilated alveoli distal to obstructed airways but DLCO  is normal or mildly elevated.

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During an FVC maneuver, the patient

 and then

; this method ensures that flow limitation has been achieved, so that the precise effort made has little influence on actual flow. %

elevated TLC is the hallmark

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FRC is more severely elevated due both to loss of lung elastic

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revealing volume change per time.

Residual volume is very severely elevated because of airway

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condition can also reduce FVC by raising RV, sometimes

(because of the severe elevation of RV ) and

rendering the FEV 1/FVC ratio “artifactually normal” with the

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 FEV 1  as a

open of small intrapulmonary airways ) are

fraction of its predicted value with TLC as a fraction of its

Central airways are normal $ Raw   is normal in “pure”

predicted value.

Both

emphysema %

 is typically reduced in airflow obstruction, this

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closure and because exhalation toward RV may take so long %

, and the ; the FEV1 is a flow rate,

recoil and to dynamic hyperinflation %

The

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Loss of alveolar surface and capillaries in the alveolar walls

The relationships among spirometry are best displayed in two plots—the (volume vs. time) and the

%

  during

oop (flow vs. volume)

arterial hypoxemia usually is not seen at rest until emphysema becomes very severe »

total resistance of the pulmonary and upper airways is measured in the same body plethysmograph used to measure FR

» »

in a slow vital capacity maneuver, the subject

,

closed and then opened shutter. Panting against the closed

, and then »

- the difference between TLC and RV, represents the maximal

shutter reveals the thoracic gas volume »

excursion of the respiratory system »

To determine absolute lung volumes, two approaches are

o

Simultaneous measurement of flow allows the calculation of lung resistance (as

»

commonly used: a. inert gas dilution

patient is asked once again to pant, but this time against a

).

In health, R aw  is very low

), and half of

the detected resistance resides within the upper airway. »

In the lung,

.

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 the time of inhalation, and its final concentration

»

reveals the volume of resident gas contributing to

against a closed shutter while pressure is monitored at the

the dilution. b. body plethysmography o

FRC is determined by measuring the compressibility

patient is instructed to exhale or inhale with maximal effort

mouth. »

Pressures   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.

»

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.

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This “single-breath diffusing capacity” (D LCO ) value within the capillaries, and it

»

Thus, DLCO

 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

  in acute

congestive heart failure, asthma, polycythemia, and pulmonary hemorrhage.

»

The effectiveness of gas exchange can be assessed by measuring

in a

sample of blood obtained by arterial puncture. »

The oxygen content of blood (Ca O2) depends upon arterial saturation (%O 2Sat), which is set by Pa O2 , 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

.

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