Chapter 11
Gas Exchange & Transport
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Learning Objectives




Describe how oxygen & carbon dioxide move
between the atmosphere & tissues.
Identify what determines alveolar oxygen &
carbon dioxide pressures.
Calculate the alveolar partial pressure of
oxygen (PAO2) at any give barometric
pressure & FIO2.
State the effect that normal regional
variations in ventilation & perfusion have on
gas exchange.
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2
Learning Objectives (cont.)




Describe how to compute total oxygen
contents for arterial blood.
State the factors that cause the arteriovenous
oxygen content difference to change.
Identify the factors that affect oxygen loading
& unloading from hemoglobin.
Describe how carbon dioxide is carried in the
blood.
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3
Learning Objectives (cont.)



Describe how oxygen & carbon dioxide
transport are interrelated.
Describe the factors that impair oxygen
delivery to the tissues & how to distinguish
among them.
State the factors that impair carbon dioxide
removal.
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Introduction
 Respiration: process of moving oxygen to
tissues for aerobic metabolism & removal of
carbon dioxide

Involves gas exchange at lungs & tissues
• O2 from atmosphere to tissues for aerobic metabolism
• Removal of CO2 from tissues to atmosphere
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Diffusion

Whole-body diffusion gradients



Gas moves across system by simple diffusion
Oxygen cascade moves from PO2 of 159 mm Hg
in atmosphere to intracellular PO2 of ~5 mm Hg
CO2 gradient is reverse from intracellular CO2 ~60
mm Hg to atmosphere where it = 1 mm Hg
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6
Diffusion (cont.)
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7
There is a stepwise downward “cascade of partial
pressures” from the normal atmospheric to the
intracellular, for which of the following gases?
A.
B.
C.
D.
CO2
O2
N
H2O
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Diffusion (cont.)

Determinants of alveolar CO2
.
.

PACO2 = (VCO2  0.863)/VA

PACO2 will increase with ↑VCO2 or ↓VA

The relationship is expressed by:
VCO (ml/min, STPD)
PA
 863 
VA (ml/min, BTPS)
.
.
2
C O2

PACO2 = arterial carbon dioxide tension (mm Hg)
 VCO2 = rate of CO2 produced (in mL /min STPD)
 VA = alveolar ventilation (mL /min BTPS)
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Diffusion (cont.)



VCO2 is expressed as flow of dry gas at 0ºC &
760 mmHg
VA reported as saturated gas at body
temperature ambient pressure
Factor 863 is employed to correct
measurement
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Diffusion (cont.)

Increase in deadspace (VD) can also lead to
increased PACO2

Portion of inspired air that is exhaled without being
exposed to perfused alveoli
.




VA = alveolar ventilation
VT = tidal volume
VD = dead space volume
f = ventilatory frequency
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11
All of the following can lead to an increased Paco2
, except:
A.
B.
C.
D.
↓ VD
↓ VA
↑ VCO2
↑ VD
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Diffusion (cont.)

Alveolar oxygen tensions (PAO2)



PIO2 is primary determinant
In lungs, it is diluted by water vapor & CO2
Alveolar air equation accounts for all these factors
PAO2 = FIO2  (PB – 47) – (PACO2/0.8)


Dalton’s law of partial pressures accounts for first part of
formula; second part relates to rate at which CO2 enters lung
compared to oxygen exiting
• Ratio is normally 0.8.
If FIO2 > 0.60, (PACO2/0.8) can be dropped from equation
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Diffusion (cont.)

Changes in alveolar gas partial tensions


O2, CO2, H2O, & N2 normally comprise alveolar
gas
• N2 is inert but occupies space & exerts pressure
• PAN2 is determined by Dalton’s law
PAN2 = PB – (PAO2 + PACO2 + PH2O)
Only changes seen will be in O2 & CO2
• Constant FIO2, PAO2 varies inversely with PACO2
• Prime determinant of PACO2 is VA
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Diffusion (cont.)
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Diffusion: Mechanisms


Diffusion occurs along pressure gradients
Barriers to diffusion



A/C membrane has 3 main barriers
• Alveolar epithelium
• Interstitial space & its structures
• Capillary endothelium
RBC membrane
Fick’s law: The greater the surface area,
diffusion constant, & pressure gradient, the
more diffusion will occur
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Diffusion (cont.)

Pulmonary diffusion gradients


Diffusion occurs along pressure gradients
Time limits to diffusion:
• Pulmonary blood is normally exposed to alveolar gas for 0.75
second, during exercise may fall 0.25 second
• Normally equilibration occurs in 0.25 second
• With diffusion limitation or blood exposure time of less then 0.25
seconds, there may be inadequate time for equilibration
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Diffusion (cont.)
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Normal Variations From
Ideal Gas Exchange


PaO2 normally 5–1 mm Hg less than PAO2 due to
presence of anatomic shunts
Anatomic shunts
Portion of cardiac output that returns to left heart without being
oxygenated by exposure to ventilated alveoli
 Two right-to-left anatomic shunts exist
• Bronchial venous drainage
• Thebesian venous drainage
• These drain poorly oxygenated blood into arterial circulation
lowering CaO2
.
Regional inequalities
in. V/Q
.
 Changes in either V or Q affect gas tensions


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Which of the following choices accurately
completes the statement, “anatomic shunts…”
A. are a portion of cardiac output that returns to
left heart without being oxygenated
B. are exposed to ventilated alveoli
C. cause the PaO to be normally 10–20 mm Hg
less than PAO2
D. are left-to-right shunts
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Normal Variations From
Ideal Gas Exchange (cont.)
.

.
V/Q ratio & regional differences
. .


. .
Ideal ratio is 1, where V/Q is in perfect balance
In reality. lungs
don’t function
. . at ideal level
.
• High V/Q ratio at apices >1 V/Q (~3.3)

↑PAO2 (132 mm Hg), ↓PACO2 (32 mm Hg)

Blood flow is ~20 times higher at bases
Ventilation is greater at bases but not 20
↓PAO2 (89 mm Hg), ↑PACO2 (42 mm Hg)
. .
• Low V/Q ratio at bases <1.0 (~0.66)


• See Table 11-1
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21
Normal Variations From
Ideal Gas Exchange (cont.)
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Oxygen Transport


Transported in 2 forms: dissolved & bound
Physically dissolved in plasma



Gaseous oxygen enters blood & dissolves.
Henry’s law allows calculation of amount dissolved
• Dissolved O2 (ml/dl) = PO2  0.003
Chemically bound to hemoglobin (Hb)



Each gram of Hb can bind 1.34 ml of oxygen.
[Hb g]  1.34 ml O2 provides capacity.
70 times more O2 transported bound than
dissolved
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Oxygen Transport (cont.)

Hemoglobin saturation


Saturation is % of Hb that is carrying oxygen
compared to total Hb
• SaO2 = [HbO2/total Hb]  100
• Normal SaO2 is 95% to 100%
HbO2 dissociation curve



Relationship between PaO2 & SaO2 is S-shaped
Flat portion occurs with SaO2 >90%
• Facilitates O2 loading at lungs even with low PaO2
Steep portion (SaO2 <90%) occurs in capillaries
• Facilitates O2 unloading at tissues
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Oxygen Transport (cont.)
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Oxygen Transport (cont.)
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Oxygen Transport (cont.)

Total oxygen content of blood




Combination of dissolved & bound to Hb
CaO2 = (0.003  PaO2) + (Hb  1.34  SaO2)
Normal is 1620 mL/dL
Normal arteriovenous difference (~5 mL/dL)
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Oxygen Transport (cont.)
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Oxygen Transport (cont.)

Fick equation




C(a  v)O
2 indicates tissue oxygen extraction in
proportion to blood flow (per 100 ml of blood)
.
Combined with total oxygen consumption. (VO2)
allows calculation of cardiac output (Qt)
.
.
Qt = VO2/[C(a  -v)O2  10]
.
Normal adult Qt is 48 L/min.
.
-v)O are due to
VO2 constant,
changes
in
C(a

2
.
.
.
changes
in Qt; i.e., ↑C(a  v)O2 signifies ↓Qt
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Oxygen Transport (cont.)

Factors affecting oxygen loading & unloading


Besides shape of HbO2 curve, many factors affect O2
loading & unloading
pH (Bohr effect)
 Describes affect pH has on Hb affinity for O2
 pH alters position of HbO2 curve
• Low pH shifts curve to right, high pH shifts to left
 Enhances oxygen transport
• At tissue pH is ~7.37 shift right, more O2 unloaded
• Lungs pH ~7.4 shifts back left, enhancing O2 loading
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Oxygen Transport (cont.)
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Oxygen Transport (cont.)

Body temperature (T) & HbO2 curve

Changes in T alter position of HbO2 curve
• Decreased T shifts curve left
• Increased T shifts curve right
• T is directly related to metabolic rate


When T is higher, right shift facilitates more oxygen
unloading to meet metabolic demands
With lower metabolic demands, curve shifts left as not as
much oxygen is required.
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Oxygen Transport (cont.)
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Oxygen Transport (cont.)

2,3-Diphosphoglycerate (DPG) & the HbO2
curve

Found in quantity in RBCs; stabilizes
deoxygenated Hb, decreasing oxygen’s affinity for
Hb
• Without 2,3-DPG Hb affinity is so great that O2 cannot
unload
↑2,3-DPG shifts curve to right, promoting O2
unloading
 ↓2,3-DPG shifts curve to left, promoting loading
• Stored blood loses 2,3-DPG, large transfusions can

significantly impair tissue oxygenation
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Oxygen Transport (cont.)

Abnormal hemoglobins




HbS (sickle cell): fragile leads to hemolysis & thrombi
Acute chest syndrome (ACS), multiple causes
• Most common cause of death
Methemoglobin (metHb): abnormal iron (Fe3+) cannot
bind with oxygen & alters HbO2 affinity (left shift)
• Commonly caused by NO, nitroglycerin, lidocaine
• Must frequently monitor for MetHb & weigh risk vs. benefit
Carboxyhemoglobin (HbCO): Hb binds CO, has 200
times > Hb affinity than O2
• Displaces O2 & shifts curve left


O2 which is bound cannot unload (left shift)
Treat with hyperbaric therapy
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Oxygen Transport (cont.)

Measurement of Hb affinity for oxygen
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A factor that does not significantly affect oxygen
loading & loading is:
A.
B.
C.
D.
plasma oxygen content
pH
body temperature
the amount of 2,3-Diphosphoglycerate (DPG)
in RBC’s
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Carbon Dioxide Transport

Transport mechanisms



Dissolved in blood: ~8% as high solubility coefficient
Combined with protein: ~12% binds with amino
groups on plasma proteins & Hb
Ionized as bicarbonate: ~80% transported as HCO3
due to hydrolysis reaction
• Majority of hydrolysis occurs in RBCs as they contain
carbonic anhydrase—serves as catalyst
• HCO3 diffuses out of RBCs in exchange for Cl, called
chloride shift or hamburger phenomenon
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Carbon Dioxide Transport (cont.)

CO2 dissociation curve


Relationship between PaCO2 & CaCO2
HbO2 affects this relationship
• Haldane effect describes this relationship
• As HbO2 increases, CaCO2 decreases

Facilitates CO2 unloading at lungs
• At tissues, HbO2 decreases & facilitates higher CaCO2
for transport to lungs
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Carbon Dioxide Transport (cont.)
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Carbon Dioxide Transport (cont.)
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Abnormalities of Gas Exchange &
Transport

Impaired oxygen delivery (DO2)



DO2 = CaO2  Qt
When DO2 is inadequate, tissue hypoxia ensues
Hypoxemia: Defined as. abnormally
low PaO2
.
. .
• Most common cause is V/Q mismatch

Because of shape HbO2 curve,
. .areas of high V/Q cannot
compensate for areas of low V/Q, so ↓PaO2
• Other causes: hypoventilation, diffusion defect, shunting,
& low PIO2 (altitude)
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Abnormalities of Gas Exchange &
Transport (cont.)
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Abnormalities of Gas Exchange &
Transport (cont.)

Physiologic shunt

Where perfusion exceeds ventilation, includes:
• Capillary or absolute anatomic shunts
• Relative shunts seen in disease states diminish
pulmonary ventilation

Relative shunts can be caused by:
• COPD
• Restrictive disorders
• Any condition resulting in hypoventilation
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Abnormalities of Gas Exchange &
Transport (cont.)

Shunt equation


Quantifies portion of blood included in V/Q
mismatch
Usually expressed as % of total cardiac output:
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Abnormalities of Gas Exchange &
Transport (cont.)

Shunt Equation:



Mixed venous oxygen content can be measured from
pulmonary artery
End capillary content must be derived from additional
calculation
• Using alveolar air equation & hemoglobin concentration
Deadspace Ventilation


Ventilation that doesn’t participate in gas exchange
• Waste of energy to move gas into lungs
Two types: alveolar & anatomic
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Abnormalities of Gas Exchange &
Transport (cont.)

Alveolar Deadspace:


Ventilation that enters into alveoli without any, or
without adequate perfusion
Disorders leading to alveolar deadspace :

Pulmonary emboli
 Partial obstruction of the pulmonary vasculature
 Destroyed pulmonary vasculature (as can occur in
COPD)
 Reduced cardiac output
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Abnormalities of Gas Exchange &
Transport (cont.)

Anatomic Deadspace:




Ventilation that never reaches alveoli for gas exchange
Normal individuals have fixed anatomic deadspace
Becomes problematic in conditions where tidal volumes drop
significantly
• Significant % of inspired gas remains in anatomic
deadspace
Expressed as ratio to total tidal volume
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Abnormalities of Gas Exchange &
Transport (cont.)


In face of increased deadspace, normal
ventilation must increase to achieve
homeostasis
Additional ventilation comes at cost:

Increase in WOB
 Consumes additional oxygen
 Further adding to burden of external ventilation
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Abnormalities of Gas Exchange &
Transport (cont.)

Impaired DO2 due to Hb deficiencies


Majority of O2 is carried bound to Hb
For CaO2 to be adequate, there must be enough
normal Hb
• If Hb is low:

although PaO2 & SaO2 are normal, CaO2 will be low
• Absolute low Hb is caused by anemia
• Relative deficiency may be due to COHb or metHb
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Abnormalities of Gas Exchange &
Transport (cont.)
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Oxygen delivery to the tissues (DO2) may be
substantially impaired due to all of the following,
except:
A.
B.
C.
D.
Low Hb levels (anemia)
V/Q matching
abnormal cardiac output
presence of Carboxyhemoglobin (COHb)
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Abnormalities of Gas Exchange &
Transport (cont.)
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Abnormalities of Gas Exchange &
Transport (cont.)

Reduction in blood flow (shock or ischemia)

Hypoxia can occur with normal CaO2 if Qt is low
• May be due to:

Shock
– Results in widespread hypoxia
– Limited ability to compensate


Prolonged shock becomes irreversible
Ischemia
– Local reductions in blood flow may result in hypoxia & tissue
death, i.e., myocardial infarction & stroke
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Abnormalities of Gas Exchange &
Transport (cont.)

Dysoxia


DO2 is normal but cells undergo hypoxia
Cells are unable to adequately utilize oxygen
• Cyanide poisoning prevents cellular use of O2
• In very sick individuals (sepsis, ARDS), oxygen debt may
occur at normal levels of DO2


If oxygen uptake increases with increased DO2, then DO2
was inadequate
Demonstrates low VO2/DO2 (extraction ratio), thus dysoxia
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Abnormalities of Gas Exchange &
Transport (cont.)

Impaired CO2 removal

.
Disorders that decreases VA relative to metabolic
need
.
• Inadequate VE

Usually result of ↓VT, ↓f rare (drug overdose)
• Increased deadspace ventilation (VD/VT) caused by:


Decreased VT as in rapid shallow breathing or,
Increased physiologic dead space, as in pulmonary embolus
• Without compensation, alveolar is lowered per minute
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Abnormalities of Gas Exchange &
Transport (cont.)

. .
V/Q imbalance
• Typically, CO2 does not rise; instead, increase VE.
• If patient is unable to ↑VE, then hypercarbia with acidosis
occurs

Seen in severe chronic disorders, i.e., COPD
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Abnormalities of Gas Exchange &
Transport (cont.)
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