Nine Flashcards
In the alveoli, what things are the diffusion of all gases proportional to? What things are they inversely proportional to?
Once gases reach the alveolar parenchyma by ventilation,
absorption into the blood or excretion from it occurs not by
convection, but by molecular diffusion according to a physiological
restatement of Ohm’s law (Fig. 9.1). Diffusion of any
gas through the septal barrier and into the blood is proportional
to the alveolar epithelial surface area (SA) and the
alveolar capillary endothelial surface area (SC) comprising
the membrane available for such exchange. Quantitative
measurements on electron photomicrographs of normal lung
have estimated SA and SC to each be 50-70 m2. This symmetry
of SA and SC dimensions is perhaps not surprising, given the
importance placed earlier on good
.V
A/
.
Q matching. Alveolar
diffusion of any gas is inversely proportional to septal barrier
thickness, estimated as its harmonic mean (τS) to emphasize
statistically the thinnest regions where diffusion is presumably
favored.
Based on Ohm’s law, what things affect the diffusion of O2 and CO2 in the alveolar air spaces/capillary spaces? What is the direction and magnitude of the gradient of O2? For CO2? Why do O2 and CO2 diffuse at the same rate despite different gradients? What does that mean concerning the presentation of lung disorders? What will happen to alveolar diffusion in emphysema? Why? In edema or fibrosis? Why?
Given these lung anatomical features that affect all gases,
other factors will determine whether diffusional equilibrium is
achieved between an alveolar airspace and the blood fl owing
through its capillaries. Again by analogy to Ohm’s law, each
gas diffuses proportionally to the pressure gradient between
its “source” (P1, the higher value) and its “sink” (P2, the lower
value). For O2, P1 = PAo2 (Chap. 8) and P2 = P_vo2 as measured
by a pulmonary artery catheter, yielding a normal inwardly
directed gradient of ~60 mm Hg on room air. That gradient
is dramatically affected by both FIo2 and PB insofar as those
affect PIo2 and thus PAo2. For CO2, P1 = P_vco2, and P2 = PAco2 (=
Paco2), for a normal outwardly directed gradient of 5-6 mm
Hg and one that is less sensitive to FIo2 or PB than that for
Po2. Indeed, data in Table 3.2 were used to make this point
earlier of a tenfold larger gradient for O2 despite that the fl ow
of CO2 outward and O2 inward are nearly the same. How can this occur? Gases will diffuse at different rates, despite equal
values for SA, SC, τS, and (P1-P2), because of differing coeffi
cients of diffusivity (D), defi ned as the solubility of a gas in
aqueous media divided by its mass-dependent rate of gaseousfree
diffusion. The value of D for CO2 is ~20 times that of O2
in biological systems, implying that lung disorders will present
more often with hypoxemia (low blood O2 content) than
with hypercarbia (high blood CO2 content). One can also
appreciate that alveolar diffusion of all gases will diminish
in a disease like emphysema where SA and SC are decreased
(Fig. 9.2). Likewise, alveolar diffusion decreases in those
diseases for which τS is increased, for example during the
edema of acute lung injury (Chap. 28) or after the development
of fi brosis in some interstitial lung diseases that show a restrictive
pattern by pulmonary function test (PFT) (Chap. 24).
What is the alveolar capillary transit time at a resting Q? At a maximal Q? What is the diffusion of N2O like? CO? How are they characterized?
Given this discussion, what time constraints exist on gas diffusion
in the lung? This question can be answered by considering
capillary transit times of erythrocytes in the lung
in relation to the equilibration rate of alveolar gases with
the interiors of those red blood cells (RBCs) (Fig. 9.3). An
RBC spends ~0.8 seconds in an alveolar capillary at a resting.Q but less than 0.3 seconds when
.Q approaches maximal values. The long RBC transit time at low.Q is usually suffi cient for N2O (an anesthetic gas), CO, CO2, and O2 to equilibrate across the alveolar-capillary barrier, that is, P1 ≅ P2 for these gases near the venular end of alveolar capillaries. By
example, N2O is very soluble in blood but does not bind to
Hb. Thus, it equilibrates across the barrier regardless of the original (PAn2o-Pc’n2o) or transit time, so that its absorption is perfusion limited only by .Q. If . Q increases, then N2O uptake increases because more RBCs pass through the alveolar capillaries
in the same interval of time. In contrast, CO binds to Hb
in such large amounts that no RBC spends enough time in an alveolar
capillary to equilibrate PAco with Pc’co. Thus, the absorption
of CO is diffusion limited, and simply increasing
. Q will not
necessarily increase CO uptake. Rather, the alveolar uptake of CO and other diffusion limited gases will more likely increase
if SA and SC increase, or if τs decreases.
What is the equilibration rate of O2 like compared to N2O or CO? When does this change? What about CO2
Normally O2 has an intermediate equilibration rate to
those of N2O or CO. In healthy individuals, O2 is a perfusionlimited
gas over a wide range of
.
Q (Fig. 9.3), and at sea level
alveolar O2 uptake usually is not considered to be the ratelimiting
step to maximal O2 consumption,
.
Vo2max (Chap. 12).
However, in diseased lungs with destroyed or fi brotic alveolar
septa, O2 becomes diffusion limited during moderate exercise,
and potentially at rest despite long RBC transit times. Even in
healthy individuals, O2 becomes a diffusion-limited gas when PAo2 is reduced by a low FIo2 or by the reduced PB at high
altitude (Chap. 13).
Based on its greater aqueous solubility, CO2 diffuses into
and out of tissues ~20 times faster than O2 per mm Hg of pressure
gradient. Consequently, there is usually ample capillary
transit time for CO2 to achieve equilibrium despite its much
smaller partial pressure gradient versus O2. However, under
conditions of reduced RBC transit time or with thickening of
the alveolar septal membranes, CO2 transfer may be incomplete
and result in hypercarbia.
How is the single breath DL(CO) calculated? What does it show? What further tests can clarify results?
The long equilibration time of inhaled CO is used clinically
to estimate the single-breath lung diffusing capacity for CO (DLCO).
CCO =.Vco/(PAco − P c ´co) where carbon monoxide conductance, CCO = [DCO · (SA +SC)]/(2 · τs). Thus, the working equation for the DLCO test becomes:
(SA + SC)]/(2 · τs) = [.Vco/(PAco − P c ´co)]/DCO
Since all terms on the right side of this equation are measured
by the single-breath DLCO procedure, the test yields a
robust “lump sum” or aggregate estimate of a subject’s alveolar
and capillary surface areas available for diffusion, as well
as their alveolar barrier’s thickness as an impediment to that
diffusion. The subject’s measured value for DLCO then can be
compared with expected normative values like other spirometric
data to assess the severity of emphysema, edema, interstitial
fi brosis, or other disease processes that impact SA, SC, or τS.
What are the two components of the overall lung diffusion capacity? Describe them. What weight do they each have?
It should be emphasized that despite crossing the alveolarcapillary
membrane, O2 has yet to oxygenate the RBCs.
Therefore, the lung’s overall diffusing capacity for O2 consists
of two linked components: its membrane diffusing capacity
for O2, DMo2 representing the distance from alveolar airspace
through the surfactant liquid, tissue, and plasma layers; and
its erythrocytic diffusing capacity. As will be described in
Chap. 16, this latter component depends on the blood transfer
conductance coeffi cient for oxygen (Θo2) between Hb
and O2, and on total pulmonary capillary blood volume, Vc.
Perhaps surprisingly, the diffusive resistance of the membrane
barrier (1/DMo2) accounts for only about half of overall resistance
to O2 uptake in the lung, with the balance of that resistance
being due to the erythrocytes themselves.
What is the relationship between P(IO2), PAO2, PcO2, and PaO2? How does this relate to physiological shunt?
To this point, the Po2 gradient in the body has encountered only
one unavoidable reduction from the inspired PIo2, that occurring
in conducting airways by Dalton’s law, as O2 is displaced
by CO2 and H2O vapor. Thus PAo2 always is less than PIo2.
The preceding discussion also implies that if O2 is a perfusionlimited
gas under most conditions, then the P´ c o2 of blood draining
alveoli should equal PAo2. However, as was seen in Chap. 8,
a subject’s actual Pao2 as reported from blood gas analyses is
always at least slightly less than PAo2. Indeed, this (A − a) Po2
difference can be quite large in some patients, implying that
the higher P c ´o2 of blood draining their alveolar capillaries is
diluted downstream with blood with a Po2 nearer to that of
mixed venous blood. This venous admixture, or contamination
of well-oxygenated blood draining the alveoli by less oxygenated
blood, comprises the essence of physiological shunt.
What is the shunt equation? How are shunt studies performed? What are normal results? What is the dangerously high result? What should then be done?
.QS/.QT = (C c ´o2 − Cao2)/(C c ´o2 − C_vo2)
In practice, shunt studies are done while subjects are
breathing pure oxygen (FIo2 = 1.00). This minor intervention
permits some simplifying assumptions about the amounts of
HbO2 versus dissolved O2 needed in the calculation of total
O2 contents for each blood compartment. Shunt studies can
be done on alert or sedated patients, provided that arterial and
venous blood samples are available for determinations of Pao2
and P_vo2, blood [Hb], and mixed venous % oxygenation or
saturation, S_vo2 (%). The calculated
.Q
S /
.Q
T is generally <10%
in most healthy adults, but it may exceed 20% in disease conditions
that are characterized by low
.V
A/
.
Q ratios as described
in Chap. 8. Several examples of shunt calculation problems
are included at the end of this chapter.
Shunt fractions approaching 50% are life-threatening
and require aggressive management to restore at least
some ventilation to lung regions where
.V
A/
.
Q ratios are
extremely low. To do so often requires judicious application
of mechanical ventilation with positive end-expiratory
pressure, PEEP that attempts to provide an “air stent”
to recruit alveoli that are consolidated into a nearly solid
state by edema or are atelectatic due to excessive surface
tension recoil (Chaps. 28 and 30).
What are the different ways in which CO2 is transported? How do oxy and deoxy Hb compare in their acidic properties?
As detailed in Chap. 3, CO2 is transported in blood as:
dissolved CO2 gas by Henry’s law; as HCO3
– from dissociated
H2CO3 after CO2 combines with H2O (facilitated by
carbonic anhydrase, CA); and as HbCO2 from its reversible
binding to Hb (Fig. 9.5). Recall that deoxy-Hb is a weaker
acid than oxy-Hb and so binds H+ more readily (the Haldane
effect), particularly in active tissues where H2CO3 formation
predominates.
What is the normal PaCO2 and PvCO2? What is the Henderson Hasselbach equation? What manipulations and assumptions can be done to make it useable when blood gas levels are known? What anion/acid ration must be kept to keep the pH at 7.40? What is a normal total CO2 is mM? What part is anion and what part is acid?
PaCo2=40mmHg PvCO2=45mmHg
Taking logarithms of both sides and then substituting for H2CO3 based on Henry’s law, yields the Henderson- Hasselbalch equation (see Chap. 17 for more detailed steps): pHa = pKa + log [HCO3– ] − log [H2CO3]
pHa = pKa + log [HCO3– ] − log [(0.03) · (Paco2)]
where 0.03 represents the solubility coeffi cient to convert Paco2 (in mm Hg) at 37°C into H2CO3 (in mM). In physiological systems, the value of pKa for this fi rst dissociation is 6.10 at 37°C, and an arterial pH of 7.40 is normally carefully regulated. Thus:
pHa = 6.10 + log ([HCO3– ]/[(0.03) · (Paco2)] 7.40 = 6.10 + log ([HCO3– ]/[(0.03) · (Paco2)] 1.30 = log ([HCO3– ]/[(0.03) · (Paco2)]) 20 = [HCO3– ]/[(0.03) · (Paco2)]
Given a typical Paco2 = 40 mm Hg, a normal resting
[HCO3-] is calculated to be:
20 = [HCO3– ]/[(0.03) · (40)][HCO3– ] = (20) · (1.2 mM) = 24 mM
Thus, to achieve a stable pHa = 7.40 using the CO2 buffer
system requires maintaining an anion/acid ratio of approximately
20:1. Obviously, this 20:1 ratio can be satisfi ed by
an infi nite range of molarities for [HCO3
– ] and [H2CO3] (ie,
Paco2). Several decades ago it was presumed that all mammals
operate at Paco2 = 40 mm Hg. However smaller animals
often function with a Paco2 of 25-30 mm Hg, and have
[HCO3
– ] values that are appropriately lower, in the range of
18-20 mM. Nevertheless, at 37°C all mammals appear to protect
a pHa of ~7.40. Indeed, subsequent investigations confi
rmed that maintaining pHa near 7.40 is far more important
than is a particular value for total blood CO2 content. Among
healthy adults, total CO2 is about 25.2 mM (= 24 mM HCO3
–
+ 1.2 mM H2CO3). However this total can vary widely, such
that the measured [HCO3
– ] and total CO2 content for individuals
refl ect either acute perturbations to their acid-base balance,
or the chronic compensatory responses to such a perturbation
(Chap. 17).
What is respiratory acidosis? What are some possible acute causes? Long term causes? How is it compensated for?
Point A here and in Fig. 9.7 represents the normal,
ideal balance among pHa, Paco2, and [HCO3
– ]. If Paco2
abruptly increases toward a higher CO2 isobar, this acute
change in acid-base status to point B is termed respiratory
acidosis. In the uncompensated phase of this response,
Paco2 is too high, pHa is too low, and blood [HCO3
–] has not
increased enough to reestablish a 20:1 ratio between [HCO3
–]
and [H2CO3]. Remembering that homeostatic mechanisms
will fi rst and foremost attempt to restore a normal pHa, one
can easily predict the appropriate response. Since respiratory
impairment already exists (Paco2 is elevated), the appropriate
compensation is to move along this new Paco2 isobar toward
point D by retaining [HCO3
–] in the kidneys and thereby
regain a 20:1 ratio. Note that the uncompensated acidosis at
point B does cause a slight increase in [HCO3
– ] by simple
mass action. However, this effect is not suffi cient to correct
the acidosis unless Paco2 is allowed to increase very slowly
from 40 to 60 mm Hg.
Acute respiratory acidosis may begin with food aspiration,
heart attack, drug overdose, pneumothorax, head injury
affecting ventilatory drive, etc. Chronic acidosis with some
compensation via renal HCO3
– retention is common with
.V
A/
.
Q
abnormalities due to obstructive disease. As the term implies,
respiratory acidosis is mainly a lung disorder, whether it is
acute and uncompensated, or chronic and partially or fully
compensated.
What is respiratory alkalosis? What are some possible acute causes? Long term causes? How is it compensated for?
In the opposite direction, an individual may abruptly
increase
.V
A , causing Paco2 to fall below 40 mm Hg. Such respiratory
alkalosis is most often due to hyperventilation during
pain or anxiety (or accidentally during mechanical ventilation),
or as a direct result of exposure to environmental hypoxia,
as occurs at high altitude. In Fig. 9.8, respiratory alkalosis
is seen acutely as moving from point A to point C toward a lower Paco2 isobar. Again in attempting to reestablish pHa =
7.40, compensation will occur toward point F by promoting
renal excretion of HCO3
– . Again, such a respiratory disturbance
could maintain the 20:1 ratio of [HCO3
– ]/[H2CO3] if it occurred
slowly, since HCO3
– is eventually converted to H2CO3 by mass
action. For example, ascent to altitude can be staged slowly
enough to minimize such alkalotic increases in pHa.
What is metabolic acidosis? What are some possible acute causes? Long term causes? How is it compensated for?
Metabolic acidosis is a serious perturbation caused primarily
by the excessive production of organic acids that overwhelm
the body’s supply of [HCO3
– ]. Diabetic ketoacidosis,
septic shock, aspirin overdose, renal failure, and diarrhea are
common causes. By observing movement from point A to
point G in Fig. 9.8, the life-threatening nature of metabolic
acidosis is apparent. Respiratory compensation from point G
to point F requires lowering blood CO2 content via hyperventilation,
which consumes additional [HCO3
– ]. Thus, the 20:1
ratio for [HCO3
– ]/[H2CO3] is restored in such a manner that
if the underlying cause of acid generation is not corrected,
blood [HCO3
– ] stores are depleted, and irreversible acidosis
and death ensue.
What is metabolic alkalosis? What are some possible acute causes? Long term causes? How is it compensated for?
Numerous nonrespiratory diseases can affect pHa,
and their onset may be either acute or more chronic than
respiratory acidosis and alkalosis. Excessive ingestion
of antiacids or prolonged vomiting can induce metabolic alkalosis, shown in Fig. 9.8 as moving from point A to point
E along a constant Paco2 isobar. Respiratory compensation
occurs toward point D in the form of hypoventilation,
again to restore the 20:1 ratio between anion and acid. This
compensation increases total blood CO2 content above that
caused by the excessive [HCO3
– ] in the acute, uncompensated
phase. Assuming patients survive any immediate crisis
caused by this elevated pHa, their hypoventilation can
be reversed later to excrete the additional CO2 content that
compensation induced.
