Models for a comparative

functional
analysis
of gas exchange organs in vertebrates
JOHANNES
PIIPER AND PETER SCHEID
Abteilung Physialogie, Max-Plan&Institut
fiir experimentelle
D-3400 Gtittingen, Federal Republic of Germany

PIIPER,JOHANNES,
AND PETER SCHEID.M~~~Z~~OTa comparative functional
analysis of gas exchange organs in vertebrates. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol.
53(6): 1321-1329, 1982.-The
analysis of external gas exchange
in the various respiratory
organs of vertebrates
is based on
models with gas transport properties determined by ventilatory,
diffusive, and perfusive conductances
and by the geometric
arrangement
of medium and blood flows. The following factors
are examined: water vs. air as external medium; gas transport
properties of blood; diffusive gas transfer between medium and
blood; problems in assessing diffusion limitation
in fish gills,
amphibian skin, avian lungs, and mammalian
lungs. Finally the
limitations to the analysis imposed by various physiological
and
anatomical complexities
are discussed.
gills; skin; lungs; water-air
dium-blood
diffusion

breathing;

blood gas transport;

me-

BRIEF
REVIEW
is to provide an introduction to comparative physiology of gas exchange mechanisms in vertebrates. Emphasis has been placed on the
physical and physicochemical properties of the media
involved (air, water, tissue, and blood), the anatomical
structure of the respiratory organs, and the application
of simplified models to analysis of external gas exchange.
Many aspects of importance in respiration, such as mechanics of breathing, acid-base balance, control of ventilation and blood flow, metabolic rate, and allometric
relationships, have not been considered. The selection of
examples and literature references is not meant to be
complete or even representative and is obviously biased
in favor of work performed in our laboratory.
A general model that serves as a discussion of the basic
variables involved is presented first. Thereafter, the individual models for the different respiratory organ
types-gills, skin, and lungs-are treated. The problems
in applying simple models to the complex real gas exchange organs are pointed out throughout and particularlyin SECTIONS
IV and VI.
The interested reader is referred to recent monographs
and reviews dedicated to comparative physiology of respiration: general (7, 23, 27, 35, 51, 65, 67, 70), vertebrates
(18, 20,45, 76), fish (21, 22, 25, 56)) reptiles (ll), and birds

(10, 60).
MODEL:

gills, skin, and lungs-the external respiratory medium

(air or water) is brought into intimate contact with the
internal gas transport medium (blood). The gases02 and
CO2 are exchanged between the two media by diffusion.
To quantify the gas transport capacity of the system
in steady state, the term conductance (G) is used, which
is defined as transfer rate (M) divided by the effective
partial pressure difference (AP) (41)
G = M/AP

For convective transport, by ventilation and perfusion,

the capacitance coefficient (p) is useful; it is defined (41)
as increment in concentration (C) per increment in partial pressure (P)

CONDUCTANCES

Copyright

@ 1982 the American

Physiological

(2)

In air, p is constant for all (ideal) gases at l/RT

(R, gas
constant; T, absolute temperature); for 02 (and inert
gases)in water, p is the physical solubility (cy);for CO2 in
carbonated water at low Pcoz, /? is increased over cyby
C02-bicarbonate-carbonate
buffering (8, 39, 71). For
blood, p results from the slope of the dissociation curves
and is generally strongly dependent on the partial pressure.
The general model and the conductances are illustrated in Fig. 1.
The ventilatory conductance (Gvent.)is by definition
ti/(PI
- PE), where PI and PE are the partial pressures
of the gas species in study in the inspired and the expired
medium, respectively. It follows from the Fick principle
that Gent is equal to the product of medium flow (v
ventilation) and p for the medium (pm)
Gvent

v*prn

(3

In analogy, with partial pressures in outflowing (i.e.

arterialized, Pa) and inflowing (i.e., venous, Pv) blood
the perfusive conductance (Gperf; i.e., M/(Pa - Pv) is
given by
.
Gperf = QP
b
(4)
where /& is the capacitance coefficient in blood.
For the diffusive gas transfer between external medium
and blood, the diffusive conductance (Gdiff) is defined as
transfer rate per spatial mean partial pressure difference
between external medium and blood (Pm - Pb)

In all types of gas exchange organs of vertebrates0161-7567/82/0000-0000$1.25

(0

,B= dC/dP

THE AIM OF THIS

I. GENERAL

Me&in,

Gdiff
Society

M/(prn

pb)

(5)
1321

1322

J. PIIPER

AND

P. SCHEID

o,, whereas in water &,/PO, is about 20-30 (see

for water breathing favors CO:!
ab:ve). The high&,/&
exchange relative to that of O2 in gills compared with
lung gas exchange, for which ,&02 = Do,. Thus in dual
breathers the respiratory quotient (R) for water is higher,
and the R value for lung gas is lower than the metabolic
R (54). These relationships are visualized in the COZ-02
diagram (53). It should be noted that skin breathing (in
air or water) is similar to water ventilation with respect
to CO2/02 conductance ratio, although the main limiting
process is diffusion (see SECTION
IV).
z

III.

G eneral model for analysis of external

gas exchange.
PI and
PE refer to partial
pressures
(e.g., of 02 or COa) in inflowing
and
outflowing
medium,
Pa and Pv to those in inflowing
and outflowing
blood. pm and pb are capacitance
coefficients
in medium
and blood.
Gdiff designates
diffusive
conductance,
also referred
to as diffusing
capacity
(D) or transfer
factor (T). M are gas transfer
rates for O2 and
FIG.

1.

coa.
II.

EXTERNAL

MEDIUM:

WATER

VS.

AIR

Water differs considerably

from air in a number of
physical properties:
capacitance
coefficient
(solubility)
for gases, diffusivity
of gases, viscosity, density, specific
heat, and thermal conductivity.
All these differences affect external respiration.
But
the difference of most fundamental
importance for respiratory gas exchange resides in the different capacitance
coefficients
(p) for respiratory
gases in air and water.
This was clearly recognized for the first time by Rahn
(52) .
Po,(water)

< PO&r)

At any given partial pressure, water contains about 30

times less O2 than air (1). The extent of 02 extraction
from the respired external medium is similar in all vertebrates, about 30-70% (excluding dead space ventilation
in lung breathers),
the highest 02 utilization values usually being encountered
in fish gills. Therefore,
for the
same 02 uptake, water ventilation must be more than 10
times higher than ventilation with air.
/ho,(water)

pco,(air)

The very similar p values of water and gas for COZ,

i.e., partition coefficient close to unity, imply that the
high water ventilation required for obtaining O2 must
lead to low expired PCO~(PECO,) and to low arterial Pcoz
(Pace,) (since Pace, is in most cases similar to PEco,).
Thus Pace, in water-breathing animals is expected to be
lo-20 times lower than Pace, in air-breathing animals. In
fact, in most fish breathing well-aerated water (Pcoa < 1
Torr), Pace, is around 0.5-4 Torr (24, 40, 71).
In air-breathing fish and in many amphibians both airventilated lungs and water-ventilated gills are functional.
It is well understandable that in such cases Pace, is
intermediate between typical values of air and water
breathers (54).

This relationship results from the fact that in gasphase

GAS

TRANSPORT

BY

BLOOD

Since Gperfis proportional to both blood flow (&) and

Pb, changes in these parameters have equivalent effects
on GperfO2 Transport

by Blood

In mammalian blood, physical solubility of 02 is relatively small compared with chemical binding to hemoglobin. However, the relative role of physical solubility (LX)
becomes more important in animals with low 02 capacity
(low hemoglobin concentration) and at low temperatures,
where CYis increased. In the Antarctic icefish (Chaenichthyidae), which contains hemoglobin-free blood, all 02
transport by blood is through physical solubility (17).
For equal Oz-binding properties (see below), Do, for
blood is nearly proportional to hemoglobin concentration. Whereas blood hemoglobin concentration among
lower vertebrates is variable, it is remarkably constant
among mammals and birds, about 11-16 go100 ml-,
corresponding to an 02 capacity of 15-21 ~01%. Since an
increase in hemoglobin concentration by polycythemia
increases the viscosity of blood and leads to disturbances
of microcirculation, the physiological red cell concentration appears to represent a compromise between 02
capacitance of blood, energy requirements for the heart,
and stability of microcirculation.
Aside from the 02 capacity, blood 02 carriage is customarily characterized I) by the half-saturation pressure
of 02 (P&, 2) by Hills coefficient (n), and 3) by the
extent of the Bohr and Root effects.
The PO, value for the same saturation range increases
with decreasing Pm in a nearly proportional manner when
the general shape of the dissociation curve remains unchanged. On the other hand, the physiologically possible
range of arterial and venous PO:! is set by other factors.
Therefore, PIjomay be considered as adjusted to the PO:!
range, being not far from the venous values. This is
understandable, since around and below Psothe slope of
the O2 dissociation curve is at its maximum (if Hills n is
not close to 1.0, see below). The important dependence
of PsOon temperature and the intraerythrocyte
concentration of allosteric modifiers-inorganic
phosphate,
adenosine triphosphate, guanosine phosphate, inositol
pentaphosphate, and 2,3-diphosphoglycerate-has
been
extensively analyzed (2, 3).
For equal P5o, increase of Hills n increases the sigmoidicity of the Oz-dissociation curve. This entails an
increase of p around Psoand a decrease of p at high and
low Po2 values. Since the middle range of 02 saturation

GAS

EXCHANGE

ORGANS

IN

is physiologically most important, relatively high n values

in mammalian and avian blood are a useful adjustment.
There appears to be an increase of Hills n with increasing
O2 saturation in blood of some frogs (32) and birds (16,
31)) which would tend to make the dissociation curve
more linear in the high saturation range.
The Bohr effect (decrease of P50 with increasing pH
and decreasing Pco~) increases p of the physiological 02
dissociation curve beyond the p for constant PCO~or pH.
The decrease of 02 capacity with decreased pH or increased Pco~, designated as the Root effect, is known for
fish blood only. Its physiological significance is linked to
secretion of O2 into the swim bladder, since by the
countercurrent multiplication of this effect, probably produced by secretion of acid into blood, blood POBcan be
boosted to very high values. For O2 uptake in gills (and
for 02 release in organs), the Root effect operates in a
manner similar to that of the Bohr effect, i.e., by increase
of PO,*
CO2 Transport

AND

G AS

EXCHANGE

BLOOD:

DIFFU

BETWEEN

R;I = K*(Pl

- Pz) *A/l

(6)

The proportionality constant K, termed Kroghs diffusion

constant, is a function of the diffusing gas and the barrier
material (and temperature).
The following well-known relationship holds among K,
the diffusion coefficient (D ), and the solubility (cu)
K=

DQX

(7)

For diffusive conductance Gdiff, defined by Eq.

following important relationship is obtained

5, the

The diffusive conductance of gas exchange organs is

usually denoted as diffusing capacity (D) or transfer
factor (T).
Extent

of Diffusion

Limitation

The role of diffusion in limiting gas exchange depends

on its relation to the other limiting processes,ventilation
and perfusion. Quantitatively,
the extent of diffusion
limitation is determined by the conductance ratios Gdiff/
Gpsrfand GdifdGvent (44). Roughly, values higher than 10
for these ratios mean insignificant diffusion limitation
and values from 10 to 0.1 imply increasingly important
diffusion limitation, whereas at values below 0.1 gas
transfer is practically exclusively diffusion limited.
As an example, the following conductance ratios were
found in resting dogfish, Scyliorhinus
stellaris
(44)
for 02

GddGperf = 0.51; Gdiff/Gvent = 1.21

for CO2

GcdGperf = 0.45; Gdiff/Gvent = 0.41

These figures, which are significantly lower than those
expected for humans (44, 46, 48), indicate a strong diffusion limitation in the branchial transfer of both CO2 and
02. It is remarkable that the ratios for CO2 are smaller
than those for 02 meaning more diffusion limitation for
CO2 transfer than for 02 transfer, although the K value
(for tissue and water) is much higher for COZ. This
behavior can be understood when the following relationship, obtained by combining Eqs. 8 and 4, is considered
(48)

MEDIUM

SION

Although an exact analysis of diffusional transport is

expected to be difficult, useful approximate solutions are
expected when simplified models are used.
Diffusive

gas species are P1 and Pa. According to a modified Fick

diffusion equation the transfer rate (M) across the barrier
is proportional to the partial pressure difference (PI Pz) and to the ratio of surface area to thickness (A/Z)

by Blood

Although the physical solubility of CO2 ((xco,) is about

20 times higher than that of 02 in blood, the major part
of COa is transported in chemical combination, mainly as
bicarbonate. By reversible bicarbonate formation pcoz is
much increased over cyco,.
The reversible formation (and decomposition) of bicarbonate is due to the action of nonbicarbonate buffers.
Thus pcoz for blood, at a given Pco~, increases with
increasing nonbicarbonate buffering power, usually
measured as buffer value for true plasma or whole blood.
Since the most important buffer of vertebrate blood is
hemoglobin (at least in blood with moderately high hemoglobin concentration), the buffering power is related
to the O2 capacity. Increasing [HCOT] at constant buffer
value also results in increased&,
for any given Pco~.
Due to the progressively increasing slope of the CO2
dissociation curve with decreasing Pco~, pcoz is higher at
lower Pco~. Since in fish blood PCO~ is very low (see
above), /?co, is usually higher than in mammals, in spite
of lower buffer value due to lower hemoglobin concentration.
The Haldane effect, i.e., the dependence of blood COa
content, on 02 saturation of hemoglobin at constant Pco2
is analogous to the Bohr effect, increasing the physiological pco, over the value for constant O2 saturation. In
mammalian blood, the relative importance of the Haldane effect for p co, seemsto be much higher than that of
the Bohr effect for PO,.
IV.

1323

VERTEBRATES

Conductance

The simplest model is a flat homogeneous layer, of

uniform thickness, separating two well-mixed infinitely
large compartments in which the partial pressures of a

The lower Gdiff/Gperf for CO2 is due to the fact that

pco, exceeds PO, by a factor that is larger than the COJ
02 ratio for K(=D*(x).
Diffusion-Limited

Exchange

of CO2 and

02

In a number of cases gas exchange is predominantly

limited by diffusion. This has been established for the
cutaneous gas exchange of a lungless salamander (42).
Diffusion-limited gas exchange has been studied in particular detail in avian eggs (49, 74).

1324

J. PIIPER

In these cases the COZ-02 relationships

are of particular interest. For their analysis Rahn et al. (55) have
proposed the concept of diffusion R lines, in analogy to
the conventional
ventilation
R lines in the COZ-02 diagram. The slope of the diffusion R lines is given by the
relationship
ensuing from Ficks diffusion law
APcoJAPoz

= R~[(D40,/(Ddco,]

(10)

Since for the gas phase ~o,/aco, equals unity and the
ratio Do~/Dco~ is about 1.4, the slope of the diffusion R
lines for R = 0.85 is about 1.2.
For the lungless salamander,
Desmognathus
fuscus,
the cutaneous gas exchange has been shown to be mainly
diffusion limited (42). Since the KcoJKo:!
ratio for tissue
is about 20, the slope of the diffusion R line for R = 0.85
is about 0.043. This value is close to the convection R
line for wat.er breathing (see SECTION
II).
Therefore the
low PCO~ measured in mixed cardiac blood of these
animals (6 Torr) becomes understandable.
Problems in Assessing Diffusion
Real Organs vs. Models

Limitation:

In the preceding analysis the gas transport

conductantes-convection
in medium and blood, diffusion in a
barrier separating
medium and blood-constitute
the
components of a simplified model. Important
discrepancies to real gas exchange organs include the following.
First, the exclusive localization of all resistance to diffusion into a homogeneous barrier separating medium and
blood does not correspond
to reality. Second, the gas
exchange organs display functional inhomogeneity.
Resistance
to diffusion in external medium. The medium is certainly not sufficiently
mixed when in contact
with the respiratory
membrane and, therefore, must offer
some resistance to diffusion. This is particularly
the case
when the medium is water because of the much smaller
diffusivity
of 02 and CO2 in water compared with air (1).
The effects of diffusion limitation in interlamellar
water
of fish gills have been. analyzed using models (61). Comparison with experimental
data on overall branchial gas
exchange indicated that a considerable
fraction of the
resistance to 02 uptake is probably located in interlamellar water (63).
The question as to whether
diffusion limitation
in
alveolar space (termed stratification)
is significant for gas
exchange of mammalian lungs is much debated. Attempts
to quantitate the resistance to gas exchange provided by
alveolar gas have indicated that it is smaller than the
tissue barrier resistance but not negligible (38, 64).
In the air capillaries of avian lungs gas transport
probably occurs by diffusion alone. Model calculations suggest
that respiratory
gas gradients in air capillaries probably
exist but that their limiting effect on gas exchange is
small due to the particular
anatomical arrangement
of
air and blood capillaries (59).
Resistance
to diffusion
within
blood and finite reaction rates. Within blood, 02 has to diffuse through
plasma, red cell membrane, and red cell interior before it
reacts with hemoglobin. The kinetics of this reaction may
also exert a limiting effect, particularly at low body
temperature in poikilotherms. In spite of much effort the

AND

P. SCHEID

attempts to partition the total resistance to 02 uptake in

mammalian lungs into a membrane and a blood
fraction (which comprises the resistance due to reaction
limitation) have not yielded conclusive results (47).
For CO2 transfer in mammalian lungs, the role of
dehydration of carbonic acid and bicarbonate-chloride
exchange between red blood cells and plasma in limiting
the exchange rate seems to be more important than
diffusion of CO2 through the blood-gas barrier proper (29,
73). These limitations are expected to be more important
in fish gills (6), where it has been postulated, based on
experimental data, that the CO2 exchange is mainly
governed and limited by carbonic anhydrase activity in
the gill epithelium and by plasma-water ion exchange
processes (14). However, major components of the theory-unavailability
of red cell carbonic anhydrase to
plasma and absence of bicarbonate transfer between
erythrocytes and plasma- have not been confirmed by
others (37). Evidently this important issue awaits further
investigation.
Effective conductance. When evaluating experimental data, all the diffusion and reaction limitations mentioned above are usually lumped into one effective conductance, termed diffusing capacity (D) or transfer factor (T). D is then defined as diffusive conductance, Gdiff,
i.e., transfer rate, u, divided by the mean effective partial
pressure difference between medium and blood, (Pm Pb). This is reasonable only if M is proportional to the
effective partial pressure difference. With chemical reactions this is true only if the reaction velocity is at least
approximately proportional to the partial pressure difference between the actual and the equilibrium value (firstorder reaction with respect to 02 and COZ).
Inhomogeneities. All gas exchange organs consist of
numerous units (secondary lamellae of fish gills, alveoli
of mammalian lungs, parabronchi of avian lungs) arranged essentially in parallel. It can be stated quite
generally that if any of the variables influencin .g the
conductances, i.e., ir, &, or diffusing conditions, are different among the units (functional inhomogeneity) the
total gas exchange efficiency of the system is reduced
compared with a model in which the variables are equal
in each unit (functional homogeneity).
Pioneered by Rahn (52) and by Riley and Cournand
(58)) the effects of unequal alveolar ventilation-perfusion
(VA/Q) distribution on gas exchange in mammalian lungs
have been extensively studied. Similar studies have been
performed for avian lungs (5, 50), and analogous effects
are expected to occur in fish gills (19).
V.

MODELS

AMPHIBIAN
AND

MAMMALIAN

FOR
SKIN,

GAS

EXCHANGE

AVIAN

IN

FISH

GILLS,

LUNGS,

LUNGS

The following four models have been proposed to

describe the gas exchange behavior of the main types of
respiratory organs in vertebrates (Fig. 2): A, countercurrent model for fish gills; B, open model for amphibian
skin; C, crosscurrent model for parabronchial lungs of
birds; and D, ventilated pool model for the alveolar lungs
of mammals.
The gas exchange behavior of the models has been

GAS

EXCHANGE

Fish
Secondary

QRGANS

gills

IN

1325

VERTEBRATES

Bird

lung

Mammalian

lamellae

4lveolus

lung

Amphibian

A Ventilation

Skin

load
liar ies
Ventilator

y water

flow

Ventilatory

Counter-current

air

PO01 I

Blood

capillaries

FIG. 2. Basic
structural
and functional models for analysis of external
gas
exchange
in vertebrates.
I, inspiratory;
E, expiratory;
a, arterial;
v, venous.

Open

i=e

i
a
-e

a-c

worked out in theory and has tentatively been applied to

experimental
data (43, 44). In the following discussion,
some features of modeIs A, B, and C will be considered.
A. Countercurrent

surface

f (ow

Cross-current

skin

Model for Fish Gills

The countercurrent
flow of water and blood appears
to result from the anatomy of the gills in both teleost
and elasmobranch
fish (56).
The countercurrent
model offers the highest inherent
efficiency of all gas exchangers,
since the outflowing
blood approaches equilibrium with the inflowing medium
and the outflowing medium approaches equilibrium with
the inflowing blood.
The condition of perfect or near-perfect
equilibration
has never been observed in fish. In most cases even a
crossing-over
of blood and water partial pressures (i.e.,
and Pace,< PECO,) is not observed. This
Pa0,>
-0,
reduced efficiency may be attributed to diffusion limitation and/or to functional inhomogeneities
(unequal distribution of water to blood flow, water shunt, and blood
shunt) e
A more comprehensive
analysis of 02 transfer has been
performed in the rainbow trout (57), in the carp (24), and
in the dogfish, Scyliorhinus
stellaris (40) and S. canicula
(66)
The O2 data measured in S. stellaris could satisfactorily be explained using the estimates of the diffusion
resistances of the blood-water
barrier based on morphometric data and of the interlamellar
water based on
model calculations
(61), thus leaving little space for inhomogeneity
effects and blood shunting (63). The very
variable and frequently very low Pao, observed in some
teleosts, e.g., in the carp (24), suggests occurrence
of
considerable shunting of water or blood.
The COz exchange deserves particular interest, but its
experimental study is difficult because the PCO~ values in

water and blood are very small and close to each other.
The blood-to-water
gradients for Pco~, usually about 2
Torr, are even smaller than anticipated from 0% exchange
on the basis of Kroghs diffusion constants for tissue (40).
This high efficiency of blood-water
CO2 equilibration
may be interpreted to indicate that limitation by reaction
kinetics is of minor importance
or that 02 exchange is
depressed due to inhomogeneity
or reaction kinetics.
B. Open Model for Amphibian

Skin

Cutaneous gas exchange is important in all amphibians

and is the sole mode of respiration
in lungless salamanders (all plethodontids
and some representatives
of other
groups). Moreover, cutaneous respiration plays a varying
role in many reptiles and fish (see below).
The model for cutaneous respiration,
a blood capillary
equilibrating
across a tissue layer with a medium of
coiistant composition,
is the same as that used for analysis of gas exchange in mammalian lungs (where alveolar
gas is substituted
for environmental
medium) (47).
A detailed analysis of cutaneous gas exchange in the
lungless salamander Desmognathus
fuscus (42) showed
that both 02 uptake and CO2 output are mainly limited
by diffusion. The marked decrease of 02 uptake observed
in hypoxia in this animal appears to be a necessary
consequence of this diffusion limitation.
In most cases cutaneous gas exchange occurs beside
pulmonary
gas exchange. One observes in these cases
that the respiratory
quotient (R) of skin breathing is
considerably higher than that of pulmonary gas exchange
(54). This behavior is explained on the basis of a comparison of the conductance
values. Cutaneous
gas exchange is limited by tissue (water) diffusion, for which
GCO~ is considerably
higher than Goz, and by blood flow.
Hence, cutaneous gas exchange contributes
significantly
more to CO2 excretion than to 02 uptake, which occurs

1326

J. PIIPER

predominantly
in the lung. This behavior is independent
of the outer medium of cutaneous gas exchange (air or
water).

TABLE

diffusing

Model

for Parabronchial

VI.

LIMITATIONS

Variable

OF

THE

Capacitance

ANALYSIS

Coefficient

of Blood

nk

D = C D, = C (p %
n=l

n=l

rn-

)
bn

(11)

For the ventilated pool model of alveolar lungs the alveolar partial pressure (Pm) is constant, and the integration
is performed from mixed venous to arterial values. For
optimization it is recommended
to decrease the pjIn steps
in the flatter part of the dissociation curve.
For the crosscurrent
model of parabronchial
lungs, a
Bohr integration must be made for each cross-sectional
element of the parabronchus,
with Pm constant, at a
value determined by the combined &?I in upstream elements. The mixed arterial partial pressure results from

(PI

PE)

(Pa - Pv)

Crosscurrent

Ventilated

Open

pool

system

D, diffusing
capacity;
M, transfer
rate; PI, PE, Pa, and Pv, inspiratory, expiratory,
arterial,
and venpus partial
pressures,
respectively.
* When PI - PE = Pa - Pv, D = M/(PI
- Pa) = M/(PE
- Pv).

mixing of end-capillary
blood from each cross-sectional
element. Starting from PI and Pv, the experimental
&!I,
Pa, and PE are approximated
by trial and error.
For the countercurrent
model of fish gills the Bohr
integration is much simpler, consisting of a single integration starting at the one end with PI and Pa and ending
at the other end with PE and Pv.
All the procedures are also applicable to COZ. Usually
the blood CO2 dissociation curve between the venous and
the arterial values can be considered as linear, and the
equations of Table 1 may be used.
Metabolism

Only when the capacitance coefficient (p) is constant

for both medium and blood does a simple relationship
exist among Gdiff (=D), &X, and the partial pressures PI,
PE, Pa, and Pv (Table 1). These relationships
may be
used for calculation of D from experimental
data.
When ,8 is not constant, i.e., the dissociation
curve is
not linear, a summation
procedure
(Bohr integration)
has to be used.
In principle, the diffusion barrier is partioned into N
elements of identical transfer rate, M, = P;I/N, and t,he
diffusing capacity of each element, AD,, is calculated as
the ratio of u, to the partial pressure difference between
medium and blood of the element, (Pm - P&. The
elements are made sufficiently
small to ensure that (P,
- P& can be regarded as constant within each. Total D
is then the sum of the AD, values
N

Equation

Countercurrent

The appropriateness
of the crosscurrent,
or serial-multicapillary,
model for analysis of gas transfer in avian
lungs is supported by the experimental
finding that reversal of gas flow in parabronchi
does not alter the
efficacy of air-blood gas transfer (62) as well as by anatomical evidence (9).
As for maximum inherent efficacy, the crosscurrent
model is inferior to the countercurrent
model. However,
for COa exchange the crosscurrent
model can achieve an
unexpectedly
high efficiency when combined with the
Haldane effect, which enables end-expired Pcoz to exceed
P&o, (33)
Comparison
of the performance
of the crosscurrent
model of avian lungs with the ventilated pool model of
mammalian lungs clearly shows the higher efficacy of the
crosscurrent
system. However, the Pao, is usually found
to be lower than end-expired PO, also in birds, although
the model predicts the reverse for the ideal crosscurrent
model. Apparently
diffusion limitation
and functional
inhomogeneities
reduce the overall gas exchange efficiency, more for O2 than for COS.

P. SCHEID

1. Equations
for calculating
capacity for the various models

Model

C. Crosscurrent
Lungs of Birds

AND

of the Exchange

Organ

The analysis of gas exchange is based on the assumption that the O2 consumed and the CO2 produced by the
gas exchange organ are of no influence, either because
their metabolism
is small in relation to the body or
because the 02 requirement
of the gas exchange organ is
covered from other sources (arterial blood).
The 02 consumption
of mammalian lungs appears to
be small when related to the total 02 uptake. Fish gills,
however, are the site of energy-consuming
active electrolyte transport and therefore are expected to have a higher
02 consumption
(and CO2 production).
Based on measurements in isolated teleost gills, about 7% of the total
02 consumption
was estimated to take place in gills (26).
Gas Exchange

at Accessory

Sites

Aside from amphibians,

in which it plays a major,
predominant,
or even exclusive role (see above), cutaneous gas exchange has been shown to play a role in fish
(28, 36)) reptiles (13)) and even mammals (bat wings, see
Ref. 15).
This accessory cutaneous gas exchange, if not taken
into account, may cause misestimation
of pulmonary or
branchial gas exchange when this is related to the 02
uptake and CO2 output measured for the whole body.
Unsteady

State

The simplified approach presented

in this paper is
applicable to steady-state
gas exchange only. This means

GAS

EXCHANGE

ORGANS

IN

that all the conductances are constant in time. In reality,

this is never strictly the case. Ventilation is always cyclic,
as is cardiac activity. In spite of this, in animals breathing
regularly and not too slowly (mammals, birds, and fish in
most cases)ventilation and blood flow may be considered
as continuous with sufficient accuracy.
In amphibians and reptiles, however, very slow or
grouped breathing (several consecutive breaths preceded
and followed by apneic periods) is common. In such
cases,more elaborate models containing capacitances for
O2 and CO2 have to be used for analysis of gas exchange
and transport. In diving air breathers the capacitances,
which are measures for the availability of 02 and CO2
stores, become of prominent importance.
Connection
to External
Dead Space Ventilation

1327

VERTEBRATES

Medium:

Lungs are connected to the external body surface by a

duct in which little or no gas exchange takes place and
which therefore constitutes a respiratory dead space. In
mammals, the effect of this anatomical dead space on
pulmonary gas exchange is usually taken into account by
defining an effective or alveolar ventilation calculated as
total ventilation minus dead space ventilation (in reality,
the ventilation of alveolar space is close to total ventilation, part of which is ineffective because it represents
reinspiration of alveolar gas from dead space) and by
using alveolar partial pressure (PA). Thus V and PE in
the models (Fig. 1, Table 1) are replaced by their alveolar
counterparts, VA and PA.
Since in bird lungs there is no mixing pool comparable
with mammalian alveolar space, application of such a
procedure appears unwarranted.
Fish are sometimes said to have the advantage of
having no dead space because their ventilation is unidirectional. But water flow bypassing the interlamellar
spaceswould functionally correspond to dead space ventilation. Moreover, water moving fast in the central
stream through the interlamellar spaces may have very
little gas exchange and therefore constitute dead space
ventilation. One may consider the diffusion limitation in
interlamellar water as due to a functional dead space
ventilation. It is of interest to realize that the dead space
in mammalian lung is also due to limited diffusive (and
convective) mixing of inspired gas with lung gas.
Connection
to the Circulatory
System:
Vascular
Shunting
and Mixing

According to the general arrangement of the circulatory system and to its connection with the respiratory
organ it can only be expected in fish, birds, and mammals
that 1) systemic arterial blood is essentially identical
with the blood leaving the respiratory organ and 2)
respiratory organ perfusion is close to the body perfusion
(cardiac output). In amphibians and reptiles central (intracardiac and extracardiac) blood mixing may lead to
considerable deviations from these conditions.
However, in fish there is also anatomical or functional
evidence for the following kinds of accessory vascular
pathways (30, 68, 72): 1) channels leading from afferent

to efferent branchial arteries bypassing secondary lamellae; 2) vessels leading from parabranchial arteries via the
central vein of the filament to the venous system; and 3)
anatomically more numerous connections between postbranchial arteries and the venous system of the filaments
(this is probably the nutritive circulation of the gills,
analogous to bronchial circulation in mammals).
From the viewpoint of gas exchange, vessels of type 1
would lead to a true shunt or venous admixture to
postbranchial blood, whereas the vessels of types 2 and
3 would decrease the extent of extrabranchial body perfusion relative to gill perfusion, but they would not produce venous admixture. These alternative pathways
should also be considered if effective gill perfusion or
cardiac output is calculated from branchial 02 uptake
and systemic arterial-to-mixed venous 02 concentration
difference (Fick principle).
In reptiles, with the exception of the crocodiles, the
ventricular septum is incomplete, and in crocodiles there
is an opening (foramen Panizzae) between the roots of
the arterial trunks originating in the left and right ventricles. Thus in all reptiles blood mixing between the
right and left heart or their outflow channels is possible
and has been observed (75). In lizards simultaneous rightto-left and left-to-right shunt has been observed (4).
Since in amphibians the ventricular septum is totally
lacking, the finding of rather restricted arteriovenous
mixing in the bullfrog is remarkable (69). Further complications arise from the fact that part of the skin is
supplied by systemic arterial branches (with arterialized
blood), part by venous blood via the pulmocutaneous
artery (34). The outflow of blood from the skin is to the
venous system. The external gills, when persisting in the
adult, are functionally similar to skin, but their blood
outflow is into the arterial system (like in fishes). In the
lungless plethodontids, in which skin (and buccal mucosa) is the only site of gas exchange, the circulatory
system is secondarily simplified into a system where the
gas exchange organ is in parallel to the systemic capillaries (in contrast to fish, birds, and mammals) and where
all organs, including skin, receive blood of the same
composition (mixed cardiac blood) (12).
VII.

CONCLUSION

The analysis of external gas exchange on the basis of

ventilatory, diffusive, and perfusive conductances has
been worked out for models of various vertebrate gas
exchange organs and applied to experimental data obtained in fish, a skin-breathing salamander, birds, and
mammals. The studies performed in only a few species
should be confirmed and complemented by more elaborate investigations on related species representing various biological adaptations.
A number of complicating factors, in particular lack of
steady state, circulatory shunting, and presence of multiple gas exchange organs with varied vascular connections, render the analysis difficult in most amphibians
and in reptiles. But their strategic phylogenetic position
within vertebrates, their great diversity of respiratory
adjustments, and their apparent conservatism call for

1328
further investigation
animal groups.

J. PIIPER

of the respiratory

function

in these

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