Respiratory physiology

Yonas Ademe
Feb, 2017

1
Pulmonary Gas Exchange

2
 Introduction
• The term gas exchange refers to both the uptake
of oxygen and the elimination of carbon dioxide
• The human respiratory system supplies oxygen
through the combined processes of convection
(bulk flow) and diffusion
• The alveolar surface, on the order of 50 to 100
m2, provides a large area for diffusion of gas into
the blood

3
Cont.

4
 Cont.
• Oxygen consumption and carbon dioxide
production occur in the mitochondria and vary
with the metabolic state
– At rest, both are on the order of 200 to 250
mL/min, but this can increase to 1 L/min with
brisk walking and 3 L/min with running

5
 Physics of Gases
• Ideal gas law
– PV = nRT
• n is the number of moles, R is the universal gas constant, and T is in degrees
Kelvin
• Charles's law
– At constant temperature, pressure and volume are inversely
proportional
• Boyle's law
– At constant pressure, gas volume is directly proportional to
temperature
• Avogadro's law
– Under standard conditions of 0°C and 1 atmosphere, 1 mole of an
ideal gas occupies 22.4 L 6
 Cont.
• Because the volume and temperature of all
gases in a mixture are equal, it follows that the
partial pressure of any gas is proportional to
its mole fraction, Fx (Dalton's law)
– PX = Ptotal × Fx
• For oxygen at sea level, this becomes
– 760 × 0.21 = 160mmgh

7
 Cont.
• The rate of gas diffusion in the liquid phase is
described by a modification of Fick's law

• Factors
– Pressure gradient
– Surface area
– Distance
– Solubility coefficient

8
 Atmospheric Gases
• The composition of Earth's atmosphere is
assumed to be constant at 79% nitrogen and 21%
oxygen (dry), with a negligible amount of carbon
dioxide present (0.03%)

• Atmospheric pressure varies according to altitude

and meteorologic conditions
– Changes due to weather are on the order of 0.5% and
do not affect respiratory physiology
9
 Cont.
• Much larger variations are seen with changes in altitude
– At sea level: 760 mm Hg
– A typical commercial airliner flies at an altitude of 29,000 feet
(equivalent to the summit of Everest), where the pressure is
approximately 230 mm Hg
– At 33,000 feet, the pressure drops to 200 mm Hg and it is no
longer possible to maintain a normal inspired PO2 while
breathing 100% oxygen
– At 63,000 feet, barometric pressure equals water vapor
pressure, body fluids boil, and alveolar PO2 and PCO2 fall to zero

10
 Alveolar Gas
• Whereas all alveoli share the same inspired
and mixed venous gas composition, perfusion
and ventilation vary throughout the lung
– In the normal lung, gravitational effects cause the
ventilation:pefusion to be higher at the apex than
at the base

11
 Cont.
• Decreased inspired PO2 will cause a decrease in alveolar
PO2
– This can be the result of a change in the fractional
concentration of inspired oxygen (FIO2), as with the
administration of a hypoxic gas mixture during anesthesia or the
result of a decrease in barometric pressure

• Under normal circumstances, inspired PCO2 is zero

– Asphyxiation due to a lack of fresh air supply is the result of
rebreathing gas with progressively higher PCO2 and lower PO2

12
 Oxygen Carriage in Blood
• There are two forms of oxygen carried in the blood: that
in true solution and that in chemical combination with
hemoglobin
• The largest component of blood oxygen is contained in
hemoglobin
• Hemoglobin is a molecule made up of a protein (globin)
and four iron-containing porphyrin rings (heme)
• Each heme group is capable of binding one oxygen
molecule; hence each molecule of hemoglobin can bind
four molecules of oxygen
13
 Cont.
• Like dissolved oxygen, the
amount of oxygen in
chemical combination with
hemoglobin is a function of
PO2
• However, once all the
available sites on
hemoglobin have been
saturated, bound oxygen
becomes independent of PO2

14
 Cont.
• Once arterial saturation has reached 100%,
increasing the inspired PO2 will not result in any
significant increase in oxygen content

• Only with hyperbaric oxygen administration can

dissolved oxygen be increased to significant
levels

15
 Cont.
• Increased temperature, low pH, and high PCO2 all
cause the curve to shift to the right, facilitating
oxygen unloading to tissues with high metabolic
activity

• A decrease in 2,3-diphosphoglycerate, such as

seen with stored blood, causes a left shift in the
curve and impairment of oxygen unloading,
although this is of uncertain clinical significance
16
 Carbondioxide Carriage in Blood
• Carbon dioxide is also carried in the blood in true
solution and in chemical combination with
hemoglobin (carbaminohemoglobin), but by far
the largest quantity of carbon dioxide is in the form
of bicarbonate ion
– Bicarbonate accounts for approximately 90% of the
carbon dioxide in the blood

• The solubility of dissolved carbon dioxide gas is 20

times greater than dissolved oxygen
17
 Cont.
• The relation between
total carbon dioxide
content and partial
pressure is steeper and
relatively linear in
comparison with the
sigmoid shape of the
oxygen dissociation
curve
18
 Diffusion Block
• Ideally, one would like to measure the diffusing
capacity of oxygen, but this is impractical because
the partial pressure of oxygen in the capillary
cannot be directly measured
– This problem is overcome by using carbon
monoxide(DLCO), a gas so highly soluble in blood that
the capillary partial pressure remains essentially zero
along the length of the capillary
• In the single-breath method, the patient inhales a gas mixture
containing a known quantity of carbon monoxide and helium
• Helium is relatively insoluble and is used to calculate the lung
volume 19
 Cont.
• The following factors will result in an
increased DLCO:
– Low oxygen saturation
– Increased distance between alveolus and red
blood cell
– Decreased total surface area
– Anemia
– Decreased blood volume

20
 Ventilation/Perfusion Mismatch
• V/Q mismatch exists when the ratio of ventilation to
perfusion is not homogeneous throughout the lung
– Even healthy lungs exhibit some degree of heterogeneity
owing to the effects of gravity on blood flow and lung
compliance
• It indicates that some alveoli are hypoventilated
whereas others are hyperventilated
• Because of the differences in their solubility curves,
oxygen is much more affected by V/Q mismatch than is
carbon dioxide
21
 Cont.
• Hypoxemia due to V/Q mismatch will respond to
an increase in FIO2 or an increase in total
ventilation as long as there is some degree of
ventilation present in the low V/Q units

22
 Cont.
• Areas in which there is perfusion but no ventilation
whatsoever (V/Q = 0) represent intrapulmonary shunt
• The primary cause of intrapulmonary shunt is airspace
disease
– This can be broadly classified into alveoli that are collapsed
versus alveoli that are filled
• Pneumothorax, atelectasis, and right mainstem intubation are
common causes of alveolar collapse
– Reexpansion of alveolar collapse is accomplished with suctioning,
endotracheal tube repositioning, or chest tube placement
• Alveoli may be filled with edema (CHF, ARDS), blood (contusion), or
pus (pneumonia)
– Diseases associated with filled alveoli will often respond to positive end-
expiratory pressure, indicating that some alveoli are still recruitable 23
 Cont.
• Any area in which there is ventilation but no perfusion
(V/Q = ∞) represents pulmonary dead space
• The trachea, bronchi, and nonrespiratory bronchioles
constitute the anatomic dead space, which occupies
approximately 2.2 mL/kg and remains relatively
constant at different lung volumes
• For this reason, alveolar ventilation will increase more
with an increase in tidal volume than with an
equivalent increase in rate

24
 Cont.
• Physiologic dead space is equal to the anatomic
plus the alveolar dead space and is a measure of
the total wasted ventilation to the lung

• Physiologic dead space ventilation is normally

25% to 35% of minute ventilation but is
increased by anything that causes pulmonary
hypoperfusion or alveolar hyperinflation

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Mechanics of Breathing

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Elastic Properties of the Lung and Chest Wall

• The lung is a volume-elastic container that tends

to deflate itself
• The deflation force exerted by the lung is termed
elastic recoil pressure
• This pressure increases with lung volume, and
the pressure required to maintain inflation
equals the elastic recoil

27
 Cont.
• Lung expansion is maintained either by negative
pleural pressure at the outer surface of the lung
or by positive pressure applied via the airway
opening to the inner surface of the lung

• Irrespective of the manner in which inflation

pressure is applied, lung recoil pressure is
considered positive and is always expiratory

28
 Cont.
• The most dependent portions
of the lung receive more
ventilation per unit of lung
tissue than the uppermost
levels
– The reason for this discrepancy
is the effect of gravity
• As one approaches the base
of the lung, there is a greater
volume change per unit of
lung tissue for the same
pressure change
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 Lung volumes
• Tidal volume: Volume of a spontaneous breath
• Inspiratory reserve volume: Volume that can still be
inspired from a spontaneous end-inspiratory position
• Expiratory reserve volume: Volume that can be expired
from a spontaneous end-expiratory position (i.e., from
functional residual capacity to residual volume)
• Residual volume: Volume remaining in the lungs after a
maximal exhalation; in normal individuals, residual
volume is approximately 25% to 35% of total lung
capacity

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 Lung capacities
• Inspiratory capacity: Maximal volume that can
be inspired from the resting end-expiratory
position to total lung capacity
• Vital capacity: Maximum volume that can be
expired after a maximal inhalation
• Total lung capacity: Volume in the lungs after a
maximal inhalation
• Functional residual capacity: Volume in the
lungs at the end of a normal exhalation
31
Cont.

32
Cont.

33
 Forced Vital Capacity
• It is perhaps the most frequently used objective clinical
tool to assess mechanical characteristics of the
ventilatory system
• Analyses from the FVC include the total volume expired
and the forced expiratory volume in 1 second (FEV 1)
– Both the total FVC and the FEV1 may be reduced as a
consequence of either a restrictive or obstructive process
– On the other hand, the FEV1/FVC ratio, or the fraction of the
FVC exhaled in 1 second, is reduced by obstruction but not
by restriction in the absence of a concurrent obstruction
• For this reason the FEV1/FVC ratio is recommended as the most
reliable indicator of an obstructive ventilatory defect
34
 Peak Flow
• Peak flow can be measured either from the flow-
volume loop or with a peak flow meter

• Determination of peak flow is one test that

young children are often able to perform well
and is therefore often the best available test of
airflow obstruction in pediatric practice

35
 Vital Capacity
• Usually determined by measuring either slow or
maximally rapid exhalation from total lung
capacity to residual volume

• It is typically reduced in restrictive ventilatory

defects
– However, reduced vital capacity is not specific for a
restrictive process and may reflect gas trapping
secondary to airflow obstruction
36
 Functional Residual Capacity
• It is the volume of gas remaining in the lungs at the end of “normal”
exhalation
• During quiet breathing at rest, the FRC corresponds closely to lung
relaxation volume
• By convention, FRC is measured during quiet tidal breathing at rest
in the sitting position
• The FRC tends to be reduced in the setting of reduced chest wall or
lung compliance
• FRC is often elevated in obstructive lung disease, reflecting gas
trapping
• In neuromuscular disease, the FRC may be relatively unchanged
compared with lung volumes requiring active inhalation or
exhalation, such as the vital capacity 37
 Residual Volume
• The residual volume, air remaining in the lungs
after complete exhalation, is typically calculated
by subtracting the expiratory reserve volume
from the FRC

• Residual volume tends to be reduced in

parenchymal restrictive processes such as
pulmonary fibrosis and elevated in COPD

38
 Total Lung Capacity
• The TLC is usually computed by addition of the
separately determined vital capacity and residual
volume
• It is somewhat less reproducible than the vital
capacity because the variability in the separately
measured volume components may be additive
• Reduced TLC is the defining characteristic of a
restrictive ventilatory defect
– However, reduction is relative to the normal baseline
39
 Pulmonary Physiologic
Assessment of Operative Risk

40
 Effects of Surgery on Pulmonary Function

• Functional residual capacity (FRC) has been recognized for

decades as the single most important lung volume
measurement associated with the development of
pulmonary complications after most types of operations
• A number of factors are associated with a postoperative
decrease in FRC, including:
– General anesthesia
– Conditions that increase intra-abdominal pressure (such as obesity
and ascites, the supine position)
– The type and location of incisions used for an operation (most
important)

41
 Cont.
• No consistent changes in FRC occur after operations that
do not involve the abdomen or thorax
– FRC decreases by:
• 35% after thoracotomies
• 30% after upper abdominal operations
• 10% to 15% after lower abdominal operations
• Reduction of FRC after abdominal surgery is attributed to
both dysfunction of abdominal wall musculature and
impaired diaphragmatic function
• Even minimally invasive procedures cause diaphragmatic
and ventilatory dysfunction that is dependent on the
location of the operation 42
 Cont..
• Postoperative pain does not appear to be an
adequate explanation for these changes, which
develop despite adequate postoperative
analgesia

43
 Cont.
• The performance of a sternotomy has deleterious effects
on chest wall mechanics and postoperative pulmonary
function similar to those resulting from laparotomy,
possibly leading to pulmonary complications
– A restrictive pattern develops in the early postoperative period
that is manifested by a decrease in FRC and impaired inspiratory
and expiratory pressures
– Respiratory pressures return to normal 6 weeks postoperatively,
but FRC and other ventilatory parameters remain decreased
– A restrictive ventilatory defect is no longer evident 3 months
postoperatively

44
 Cont.
• Thoracotomy is the operative approach associated with the
highest potential risk for postoperative pulmonary
complications, owing to:
– Restricted chest wall motion
– Impaired diaphragm activity
– Possible loss of pulmonary parenchyma
• A thoracotomy incision transiently reduces most ventilatory
parameters postoperatively, with a precipitous drop occurring
by the first postoperative day
• At the end of the 2nd postoperative week, some recovery
occurs, but the deleterious effects do not resolve for almost 3
months after surgery
45
 Cont.
• Thoracoscopic operations cause a somewhat
smaller decrement in pulmonary function during
the immediate postoperative period

• The advantage persists for the first postoperative

week, after which both open thoracotomy and
thoracoscopic approaches to major lung
resection appear to have similar outcomes

46
 Cont.
• Major lung resections permanently reduce spirometric
values and diffusing capacity by varying degrees,
depending on the amount of lung that is resected
• When lung function is measured 6 months to 1 year
postoperatively
– Segmental or wedge resections result in decreases of <10%
– Lobectomy or bilobectomy results in decreases of 5% to
15%
– Pneumonectomy reduces values by 20% to 40%

47
 Cont.
• Changes in forced vital capacity (FVC) and in the forced expiratory
volume in 1 second (FEV1) during the first 3 months after
thoracotomy

48
 Cont.
• Permanent changes in FVC, FEV1, and DLCO after various types of
lung resection

49
 Lung Volume Measurements

• The measurement of lung volumes, including total

lung capacity (TLC) and residual volume (RV), is
useful in the evaluation of the lung resection
candidate

• Vital capacity is decreased when TLC is reduced by

restrictive processes, when RV is increased owing
to air trapping in obstructive disease, or by a
combination of these factors
50
 Cont.
• Restrictive physiology causes reductions in vital capacity as
well as TLC, RV, and FRC
– It is caused by pulmonary fibrosis, sarcoidosis, muscular weakness
and disease, chest wall deformities, large acquired diaphragmatic
hernias, and trapped lung owing to extensive pleural fibrosis
– In some of the cases, surgery may help resolve the restrictive
physiology, resulting in improved pulmonary dynamics
postoperatively
– But most of the causes of a restrictive physiology are not
improved by thoracic surgery, highlighting the possible risk to
these patients of major thoracic surgical procedures

51
 Cont.
• Obstructive physiology causes reductions in vital capacity,
but there are associated increases in TLC, RV, and FRC
– It is usually caused by emphysema, chronic bronchitis, and
asthma
– The use of bronchodilators and, in severe cases, inhaled or
systemic steroids can dramatically improve obstructive
physiology in patients with reactive airways disease, making
thoracic surgery much safer
– In highly selected patients with heterogeneous emphysema,
resection of the most affected regions of the lung can result in
an increase in VC
• In most other instances, the abnormal measurements are relatively
fixed, and major lung surgery further reduces vital capacity 52
 Cont.
• Relative changes in lung volumes associated
with lung diseases

53
 Cont.
• Tests of Cardiopulmonary Physiologic Status
– Spirometery
• FEV1/FVC
– FVC
– FEV1
• MVV
– DLCO
– Exercise testing
• Stair-climbing
• 6 minute walk
• VO2max
– Blood gases
54
 Spirometry Expressed as a Percentage of
Predicted Normal Values
• Authors suggested a postoperative predicted
value for FEV1 of 40% of normal as a means for
selecting patients who are at high risk for lung
resection
– A 50% mortality rate was described among patients
with a postoperative predicted FEV1 of <40% of
normal after lung resection, whereas patients with a
postoperative predicted FEV1 of >40% suffered no
operative mortality
55
 Cont.
• Care must be taken in estimating postoperative spirometric
values as a means for selecting patients for major lung
resection, especially at the lower limits of lung function

• Patients with more severe obstructive lung disease—as

defined by worse FEV1, lower FEV1/FVC ratio, or lower
diffusing capacity—experience less percentage loss of lung
function as measured by spirometry than do patients with
normal lung function
– In fact, most of these patients show relative improvement post-op

56
 Diffusing Capacity of the Lung
• It is logical that reduced diffusing capacity of the lung
for carbon monoxide (DLCO) is associated with
pulmonary morbidity and operative mortality after
major lung resection
– Substantial decreases in DLCO occur after lung resection
averaging 20% for wedge resection, 30% for lobectomy, and
41% for pneumonectomy
• Diffusing capacity is a measurement of the gas exchange
function of the lung at the alveolar–capillary interface
• It usually is measured by a single-breath technique
57
 Cont.
• The most important factor determining DLCO is the
volume and surface area of the capillary bed in
contact with alveolar gas

• Loss of alveolar surface resulting in a reduced DLCO is

most commonly seen in emphysema, but other
factors that obliterate capillaries—such as vasculitis,
embolic disease, and inflammatory interstitial
diseases—may also decrease diffusing capacity
58
 Cont.
• There are several cut-offs for preoperative DLCO (40%, 60%)
• Most physicians understand there is a close relationship between
spirometry and DLCO, such that patients with poor spirometry have
poor DLCO, and those with good spirometry have good DLCO
– While this is correct in general, individual patients can have widely
disparate values for DLCO and FEV1
• In patients without COPD (defined as FEV1/FVC ratio <0.7), DLCO is an
important determinant of postoperative pulmonary complications
– Indeed, in this group of patients, DLCO impairment is a stronger predictor of
pulmonary complications than it is in patients who have COPD
• Thus, measurement of DLCO in all lung resection candidates is
recommended
59
 Cont.
• The relationship between diffusing capacity,
age, and mortality after major lung resection

60
Exercise Capacity and Oxygen Consumption

• The rationale for preoperative exercise testing is to

permit identification of patients who are close to
the margin of cardiopulmonary function so that the
risks of surgery and the status of postoperative
exercise tolerance can be predicted

• Exercise testing quantifies what many believe to be

the best determinant of functional capacity: oxygen
consumption during maximum exercise, or VO2max
61
 Cont.
• The potential advantage of exercise testing over conventional
tests, such as spirometry and measurement of diffusing
capacity, is that most components that determine performance
are evaluated, including ventilatory function, gas exchange,
cardiac function, cardiopulmonary conditioning, and effort

• The disadvantages of exercise testing include:

– The need for costly resources to perform the technically demanding
versions of the test
– The lack of validation of the unsophisticated versions of the test
– The need for considerable patient effort and cooperation in order to
achieve reliable results
62
 Cont.
• Methods
– Traditional
• Currently used frequently and are clinically valuable
• Tasks (e.g)
– Ascending a specified number of steps or flights of stairs
– Walking for 6 minutes to enable measurement of the distance
covered
• Disadvantage
– They enable some quantitation of effort but do not permit
assessment of the underlying cause for an inadequate
performance

63
 Cont.
• Methods
– VO2max
• The assessment of oxygen consumption during maximum
exercise
– This requires measurement of O2 uptake, CO2 output, minute
ventilation, BP, ECG, and pulse oximetry
– Patients undergo symptom-limited incremental exercise on a cycle
ergometer or on a treadmill
• Results
– <10 mL/kg/min: extremely high risk for major lung resection
– >15 mL/kg/min: standard risk for complications
– 10 – 15 mL/Kg/min: indeterminate
64
 Blood Gases
• Substantially increased PCO2 or reduced PO2 is
likely to contribute to increased morbidity and
mortality after major lung resection
– However, the exact parameters permitting safe
surgery may never be established
• Many studies have been unable to demonstrate a
significant relationship between Hypercapnia (defined as
a PCO2 of >45 mm Hg) or arterial hypoxemia (PO2 <50 to
60 mm Hg) and the risk for respiratory complications or
mortality after major lung resection

65
 Age and Performance Status
• Advanced age is an independent predictor of morbidity and
mortality after major lung resection, with a twofold increase in
the risk for complications for each decade increase in age

• A patient's performance status is always assessed informally

during the preoperative period, but formal quantitation of
performance status using a system such as that of the Eastern
Cooperative Oncology Group (ECOG) is rarely performed by
surgeons
– Most surgeons intuitively identify patients with a performance status
of 2 (<50% of waking time out of bed, but unable to perform self-
care) to 4 (bedridden) as poor candidates for major lung resection
66
 Preoperative Evaluation for Lung Resection
(Algorithm)
• A suggested algorithm for assessing patients for lung
surgery begins with a standard evaluation that includes
a carefully performed history and physical examination,
spirometry, and measurement of diffusing capacity
– Predicted postoperative FEV1 and DLCO expressed as a
percentage of normal are calculated using the number of
functioning lung segments as the denominator and the
number of lung segments remaining after resection as the
numerator of a fraction that is multiplied by the preoperative
measured value to achieve a postoperative predicted value

67
 Cont.
• For patients with a postoperative predicted FEV1
of <40% or a postoperative predicted DLCO of
<40%, a quantitative pulmonary perfusion scan is
performed to assess regional lung function
– The postoperative predicted values for FEV1 and DLCO
are recalculated based on the results of the scintigram
– If these values remain suboptimal, blood gases are
obtained, and an exercise test to assess VO2max is
performed

68
 Cont.
• Criteria strongly suggesting inoperability
include:
– Predicted postoperative DLCO of <20%
– Predicted postoperative FEV1 <20%
– VO2max of <10 mL/kg/min
– PO2 of <45 mm Hg
– PCO2 of >60 mm Hg

69
Cont.

70
 Assessment of Risk for Other Procedures

• In prospective studies, neither hypercarbia nor reduced

spirometry values were predictive of an increased risk for
pulmonary complications after nonpulmonary thoracic
surgery

• With two exceptions, the appropriate preoperative

physiologic evaluation for the general thoracic surgical
patient has not been determined
– Those exceptions are the evaluation of the lung resection
candidate and possibly candidates for esophagectomy

71
 Cont.
• Based on retrospective studies, the physiologic predictors of an
increased risk for pulmonary complications after
esophagectomy are advanced age and reduced FEV1

• At present, routine pulmonary function testing of

esophagectomy patients is not warranted
– However, such testing is recommended for patients with clinically
evident impairment of pulmonary function and in patients who have
undergone induction chemotherapy or chemoradiotherapy to assist in
the evaluation of pulmonary risk and to enable optimized
preoperative and postoperative care for those patients determined to
be at increased risk

72
End!

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