Vol. 86, Issue 5, 1458-1459, May 1999
INVITED EDITORIAL
Invited Editorial on "Red cell distribution and the recruitment
of pulmonary diffusing capacity"
Robert E.
Forster
Department of Physiology, University of Pennsylvania School of
Medicine, Philadelphia, Pennsylvania 19104-6085
 |
ARTICLE |
THE MAMMALIAN LUNG is an amazing creation in which a
blood flow (in l/min) is conducted from vessels (in cm diameter at
first) through ever smaller and more numerous branches until they are ~7 µm in diameter, spreading a gossamer network enclosing air sacs
100 µm across, ventilated by airways that arborize down to 1/100th of
the tracheal diameter, and carry gases that exchange with the red blood
cells in a fraction of a second. The wonder is that blood
and gas flows to all these alveolar capillary beds are uniform as a
first approximation, which requires feedback control down to the
capillary level. Nonuniformity is the greatest enemy of lung gas
exchange and of the pulmonary diffusing capacity (DL). In 1957, I discussed
qualitatively the effects of all the types of nonuniformity that
affected the measured value of
DL for CO
(DLCO)
that I could conjure up (4), but I never thought of nonuniformity of
red cell distribution along a single capillary, as shown by Hsia et al.
(11).
The rate of uptake of O2 by red
blood cells in a single alveolar capillary cannot be measured by
techniques available today, but extremely useful conclusions can be
obtained by modeling, and a number of such studies have been reported
over the past two decades. In 1977, Hellums (8) concluded from a
cylindrical cell model that one-half the resistance to
O2 transport in peripheral capillaries was in the capillaries themselves, but it was not until
Federspiel's paper in 1989 (3) that a model of
O2 transport in red cell spheres
within a cylindrical capillary was studied. Federspiel concluded that
the discontinuous nature of red blood cells lowered membrane diffusing
capacity. Frank et al. (6) extended this work and modeled
O2 uptake of an individual red blood cell in a single pulmonary capillary assuming a parachute shape,
probably the commonest shape of cells in the flowing stream, and
demonstrated that not only was the flux of
O2 through the pulmonary membrane
to the surface of the cell closest to the endothelium important but
also the gas was diffusing through the plasma between the cells,
turning axially to deliver O2 to
additional cell surface. This is a much longer path but more rapid than
that through red cell cytoplasm because there is nothing to bind
O2 and impede its diffusion. Thus
a single red blood cell sufficiently distant from its nearest neighbors
that this plasma diffusion path is not encroached on takes up
O2 the most rapidly. As the number of cells in the capillary increases, the distance between cells decreases, and the path through the plasma becomes restricted, so that
the rate of O2 uptake per cell
goes down; but, of course, there are many more cells, so the total
uptake in the capillary rises but less than proportionally. A cell
shape that increases the mean diffusion path from the endothelium to
all of the total red cell surface decreases the effective membrane
diffusing capacity (3, 6).
In their article in this issue of the Journal, Hsia et al. (11) report
two-dimensional, finite-difference computations of CO diffusion across
the pulmonary membrane to the surface of a fixed number of cylindrical
red blood cells, distributed nonuniformly along the length of the
capillary. The germinal idea is that when cells are unevenly
distributed along the capillary the diffusion path through the plasma
between those bunched together is restricted; CO uptake by these cells
is reduced; and, of course, there is no CO uptake in the capillary
space they vacate. Therefore, the recast uptake by the whole capillary
is reduced. The greatest CO uptake occurs when the cells are evenly
spaced. This effect of nonuniform spacing can be large and becomes
worse as the capillary hematocrit decreases. A more uniform
distribution of red blood cells in the capillary may explain part of
the increase in
DLCO with exercise.
Hsia et al. (10) chose values obtained by Holland (9) for the rate of
CO uptake by red blood cells in milliliters per milliliter per
millimeter Hg PCO at different
PO2 to describe CO transport inside
the surface of the cell. These experimental rates are less than those
obtained in dog red blood cells by using a continuous-flow,
rapid-mixing apparatus (2), presumably because of stagnant layers in
the stop-flow apparatus (1, 15). However, this does not alter the
interesting new conclusion that nonuniforitiy of red blood cells in the
alveolar capillary decreases
DLCO.
DLCO
measured in lungs perfused with hemolysate is reported to be greater
than when perfused with a cell suspension (7); from this it has been
concluded that there is a significant diffusion resistance outside the
red blood cells in the plasma (stagnant layer). This is not necessarily
a helpful concept. First, if the red bood cells in a pulmonary
capillary are replaced by an Hb solution and all other conditions
remain unchanged, the rate of formation of HbCO in the capillaries will
increase by the physical laws of simultaneous chemical reaction and
diffusion. This is because, while the volume in which HbCO is formed
increases, the rate of HbO2
formation per unit volume does not decrease proportionally. As an
example, the red blood cell was modeled as a layer of Hb by Nicholson
and Roughton (12), and an analytic solution for the initial rate of
HbCO was obtained
|
(1)
|
where
d[HbCO]/dt is the rate of
change of HbCO concentration per
cm3 in the layer (the red cell
cytoplasm), [CO] is the concentration of CO at the surface
of the layer, b is the half thickness
of the layer in cm, d is the diffusion
coefficient of O2 in the layer, l' is the bimolecular reaction
velocity constant of CO reacting with Hb, and [Hb] is the
concentration of unliganded Hb in the layer (all concentrations are in
mol/cm3). Because red blood
cells approximately fill the capillary lumen, b should remain about the same in
hemolysate, but [Hb] would decrease. Federspiel (3) used a
relationship analogous to that above to obtain the
O2 uptake rate in cells. With
hemolysate in the capillaries, the volume in which HbCO is being formed
is greater by the factor 1/hematocrit, [Hb] would decrease
by its reciprocal, the hematocrit, that according to
Eq. 1 would decrease
d[HbCO]/dt, the rate per
cm3 by
(hematocrit)1/2. Thus the rate of HbCO formation in the
whole capillary would increase by (hematocrit)
1/2,
which is >1. Although considering the red blood cell and the capillary as semi-infinite layers is a crude approximation of their
shape, this same model has been used in several computations (6, 11),
and the principle that the rate of HbCO formed in a capillary perfused
with hemolysate is not decreased in proportion to the dilution of
intracellular Hb holds regardless of shape. This principle can be seen
in a three-dimensional finite-difference calculation of
O2 entrance into a discoidal red
blood cell. (5).
Second, and this is an intuitive observation, hemolysate fills the
volume between red blood cells, exposing Hb solution to a greater
endothelial surface and reducing the mean diffusion path from
endothelium to Hb molecule, which increases the total capillary CO
uptake rate. If one chooses to consider the diffusion path
through plasma between cells as a stagnant layer, this path certainly
disappears when the perfusate is hemolysate, but this same path also
facilitates gas exchange of individual cells.
This new form of nonuniformity in the alveolar capillaries may be
important in many clinical conditions, such as blood dyscrasies (e.g.,
anemia) and alterations in red cell adhesiveness as well as in
abnormalities of pulmonary blood flow.
| |
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J APPL PHYSIOL 86(5):1458-1459
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Copyright © 1999 the American Physiological Society
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![d[HbCO]/d<IT>t</IT> = [CO] × <IT>b</IT> − 1(<IT>dl</IT>′[Hb])1/2](/content/vol86/issue5/fulltext/1458/img001.gif)
