144 ARTERIAL BLOOD GASES
Xenopus oocytes; however, subsequent studies
showed unimpaired CO2 permeability in AQP1-de-
ficient erythrocytes, where rapid CO2 transport
occurs by a passive membrane solubility-diffusion
mechanism. Measurements of CO2 movement in the
perfused and in vivo mouse lung showed no effect of
AQP1 deletion, providing direct evidence against the
role of AQP1 in lung CO2 transport.
Aquaporins and Respiratory Disease
A small number of AQP1-deficient humans have been
identified. Although initially reported to have no phe-
notype, subsequent studies showed that they mani-
fest a urine concentrating defect that is qualitatively
similar to that found in AQP1-deficient mice. As
mentioned above, AQP1-deficient subjects have also
been found to have a small reduction in the increase
in bronchiolar wall thickness following intravenous
volume overload compared to normal controls,
though other lung phenotypes have not been re-
ported. The significance of this observation is unclear.
Together with a considerable body of data in
transgenic mice, the functional studies suggest that
aquaporins play at most a minor role in normal lung
physiology and clinically relevant states of lung in-
jury, with the possible exception of AQP5 in sub-
mucosal fluid secretion. It remains unresolved why
aquaporins are expressed at multiple sites of fluid
movement in the lung/airways, and why the expres-
sion of lung aquaporins appears to be altered in states
of stress. When available, nontoxic aquaporin-selec-
tive inhibitors will be useful to examine effects of
acute aquaporin inhibition, which may reveal lung/
airway phenotypes that might not be manifest in mice
or humans with chronic aquaporin deficiency. If sig-
nificant aquaporin-dependent phenotypes are found,
then pharmacological modulation of aquaporin func-
tion may have clinical applications, such as AQP5
inhibition in reducing glandular fluid secretions in
allergic and infectious rhinitis, or increasing AQP5
ARTERIAL BLOOD GASES
J W Severinghaus, UCSF, San Francisco, CA, USA
& 2006 Elsevier Ltd. All rights reserved.
Abstract
Blood gas analyzers consist of three electrodes measuring pH,
PCO2 , and PO2 at 371C. They were introduced in about 1960
expression/function to reduce secretion/ASL viscosity
in cystic fibrosis.
See also: Basal Cells. Fluid Balance in the Lung.
Further Reading
Agre P, King LS, Yasui M, et al. (2002) Aquaporin water
channels
from atomic structure to clinical medicine. Journal
of Physiology 542: 3–16.
Bai C, Fukuda N, Song Y, et al. (1999) Lung fluid transport in
aquaporin-1 and aquaporin-4 knockout mice. Journal of Clin-
ical Investigation 103: 555–561.
Borok Z and Verkman AS (2002) Lung edema clearance: 20 years
of progress. Invited review: role of aquaporin water channels in
fluid transport in lung and airways. Journal of Applied Phys-
iology 93: 2199–2206.
Dobbs L, Gonzalez R, Matthay MA, et al. (1998) Highly water-
permeable type I alveolar epithelial cells confer high water
permeability between the airspace and vasculature in rat lung.
Proceedings of the National Academy of Sciences, USA 95:
2991–2996.
Folkesson H, Matthay MA, Frigeri A, and Verkman AS (1996)
High transepithelial water permeability in microperfused distal
airways: evidence for channel-mediated water transport. Journal
of Clinical Investigation 97: 664–671.
King LS, Nielsen S, and Agre P (1996) Aquaporin-1 water channel
protein in lung-ontogeny, steroid-induced expression, and dis-
tribution in rat. Journal of Clinical Investigation 97: 2183–
2191.
King LS, Nielsen S, Agre P, and Brown RH (2002) Decreased
pulmonary vascular permeability in aquaporin-1-null humans.
Proceedings of the National Academy of Sciences USA 99:
1059–1063.
Krane CM, Fortner CN, Hand AR, et al. (2001) Aquaporin-5 de-
ficient mouse lungs are hyperresponsive to cholinergic stimula-
tion. Proceedings of the National Academy of Sciences, USA 98:
14114–14119.
Ma T, Fukuda N, Song Y, Matthay MA, and Verkman AS (2000)
Lung fluid transport in aquaporin-5 knockout mice. Journal of
Clinical Investigation 105: 93–100.
Saadoun S, Papadopoulos M, Hara-Chikuma M, and Verkman AS
(2005) Targeted AQP1 gene deletion impairs angiogenesis and
cell migration. Nature 434: 786–792.
Song Y and Verkman AS (2001) Aquaporin-5 dependent fluid se-
cretion in airway submucosal glands. Journal of Biological
Chemistry 276: 41288–41292.
Verkman AS (2002) Physiological importance of aquaporin water
channels. Annals of Medicine 34: 192–200.
following inventions by R Stow (CO2) and L Clark (PO2) both
dating from 1954. From these outputs, internal computers cal-
culate O2 saturation, base excess, bicarbonate, and other derived
variables such as the compensation by the body for acid–base
abnormalities. Arterial PO2 and PCO2 can be approximated using
heated skin surface ‘transcutaneous’ electrodes, which are
commonly used in premature infants and nurseries. Hemoglo-
bin oxygen saturation, SO2%, is also directly measured by

multiwavelength blood oximeters. Arterial SO2 is approximated
by pulse oximeters, which detect the arterial pulsatile variations
in red and infrared light penetrating a finger, ear, or other tissue,
a method invented by T Aoyagi in Tokyo in 1973 that became
commercially available in 1983. Interpretation of blood gases
and acid–base balance is briefly discussed. Figures include
schema of the three electrodes, a pulse oximeter probe, an
acid–base compensation diagram, and photographs of the first
three-function blood gas analyzer, a combined PO2 PCO2 trans-
cutaneous electrode in use on a child, and a pulse oximeter probe
on a finger.
Introduction
Arterial blood gas analyzers directly measure pH,
PCO2 and PO2 , (mmHg or Torr) and calculate stand-
ard base excess (SBE), bicarbonate (HCO3
), oxygen
saturation (SO2), and other variables useful in diag-
nosis and clinical management of patients in emer-
gencies, anesthesia, surgery, recovery, and intensive
care. These tests were rarely done until the 1950s
when electrodes were invented and developed. Un-
derstanding of acid–base and blood gas theory de-
pended on discoveries in physical chemistry.
Ionic Theory
Electrochemistry and physical chemistry of solutions
of acids, alkalis, metals, and salts were transfor-
med from empiricism to theory by the 1884 thesis
of Svante Arrhenius in Uppsala, Sweden. Wilhelm
Ostwald then used a platinum electrode to measure
hydrogen ion strength electrically. In 1893,
Ostwald’s student Walther Nernst applied the long-
established laws of gases to ions in solution to cal-
culate the electrical potential of batteries or cells.
Buffers
Shortly after 1900, Lawrence J Henderson at Har-
vard adapted the mass action law to relate [H þ ] to
PCO2 and HCO3
:
K ¼ ½Hþ ½HCO

3 =H2 CO3
He demonstrated how respiration could buffer met-
abolic acids by reducing PCO2 . The kidneys can also
change blood and extracellular fluid buffer base
to partially normalize pH in respiratory acidosis or
alkalosis.
Origin of pH
In order to define H þ ion concentrations such as
0.000 000 04 moles liter
1 (e.g., in blood) more ele-
gantly, in 1907, S P L Sørensen suggested defining
pH as the negative log of hydrogen ion concentration
(or activity). In 1915, K A Hasselbalch converted
Henderson’s equation to log form, later dubbed the
ARTERIAL BLOOD GASES 145
Henderson–Hasselbalch (HH) equation:
pH ¼ pK0 þ log½HCO

3 =SPCO2 
In plasma, pK0 ¼ 6.1, the effective dissociation
constant of H2CO3 (carbonic acid), calculated as S
PCO2 . S is CO2 solubility, 0.031 mM l
1 Torr
1.
HCO3
is plasma bicarbonate content calculated as
plasma [CO2 content – SPCO2 ].
Electrodes
pH Electrode
In 1905, Max Cremer noted that hydrogen ions per-
meated some kinds of very thin glass, developing
electrical potential gradients across the glass. Fritz
Haber and Z Klemensiewicz made the first glass pH
electrode in 1909. Its potential was a linear function
of pH, not H þ ion concentration. In 1925, the first
glass cup-shaped blood pH electrode was produced
by Phyllis T Courage. By 1933, capillary blood pH
electrodes were being made commercially. Blood pH
was corrected to 371C with the Rosenthal factor
(
0.0147 1C
1) until thermostatted blood pH elec-
trodes became available in the 1950s. A pH and ref-
erence electrode is schematically shown in Figure 1.
Details Special glass compositions permit hydrogen
ions to diffuse through imperfectly annealed sub-
microscopic cracks, probably exchanging loci with
loosely bound alkali cations, especially lithium. Some
pH electrodes are sensitive to very high Na þ con-
centrations. At 371C, the electromotive force (EMF)
across the glass measured with reference electrodes
(usually silver–silver chloride) is 61.5 mV per pH unit
change (a 10-fold change in H þ ion concentration).
Sample
Glass body
AgCl internal reference
H+ permeable
glass
Liquid junction
Saturated KCl
AgCl reference
Sample
Figure 1 Schema of a blood pH electrode with a liquid junction
to a reference electrode in a thermostatted cuvette.
146 ARTERIAL BLOOD GASES
For use in blood, the reference electrode usually con-
tacts blood via a liquid junction containing saturated
KCl. Rapid diffusion of K þ into red cells causes an
often-ignored error of
0.01 pH at the liquid junc-
tion when calibration is done with aqueous buffers.
PCO2 Measurement
Until the worldwide polio epidemics of 1950–52,
PCO2 was measured by the HH equation. This re-
quired measuring plasma CO2 content by acidifica-
tion and extraction in a manometric Van Slyke
apparatus and measuring pH and correcting it to
371C. In Copenhagen’s communicable disease hos-
pital in 1950–51, sometimes up to 100 patients at a
time were manually ventilated by volunteers using a
bag and mask with O2. The laboratory director Poul
Astrup, needing a faster analytic method than the
HH equation, devised a new simple method. He
measured pH before and after equilibrating the sam-
ple with known PCO2 . He then computed patient
PCO2 by extrapolation. His method became the
standard for the rest of the decade.
PCO2 Electrode
At Ohio State University in 1954, while also trying to
resolve the polio problem, Richard Stow invented a
PCO2 electrode. He covered a glass bulb-shaped pH
electrode with a rubber glove (through which CO2
can diffuse but H þ cannot), over a film of distilled
water. However, Stow’s electrode drifted because
various cations in pH glass altered the distilled water
pH. This electrode was stabilized by John Severing-
haus at the National Institute of Health (NIH) by
adding bicarbonate and salt, and was manufactured
by many firms from 1959 onwards. A blood PCO2
electrode is illustrated in Figure 2.
Stow–Severinghaus PCO2 electrode
AgCl external
reference electrode
AgCl internal reference
0.1M KCl + 0.01M KHCO3
Electrolyte
in paper spacer
Figure 2 Schema of a blood PCO2 electrode with Teflon CO2 permeable membrane and spacer to contain electrolyte for pH meas-
urement.
Details An internal, nearly flat, glass pH electrode
is separated from the sample by a membrane perme-
able to CO2 but not ions (e.g., Teflon or silastic).
Under the membrane, a spacer (e.g., lens-cleaning
tissue paper) holds a film of electrolyte containing
about 10 mM NaHCO3 and usually 0.1 M salt or
KCl. Thermostatted to 37oC, the output signal is a
log function of PCO2 , about 30 mV per decade in
distilled water (Stow’s design), doubling to 61 mV
per decade with bicarbonate electrolyte.
Oxygen Electrode
In 1950, Leland Clark at Antioch College, Ohio used
perfused isolated liver to study steroid metabolism.
He needed oxygenated blood so he built a bubble
oxygenator and discovered how to defoam the blood
using silicone oil on glass wool. The journal Science
rejected his paper on the basis that he hadn’t meas-
ured the PO2 in the oxygenated blood; to this end,
Clark invented a polarographic oxygen electrode. He
covered a platinum disc cathode sealed in glass with
cellophane to keep blood protein from poisoning the
cathode. It served his purpose but was not accurate,
requiring very high flow past the sensor due to the
depletion of oxygen at the membrane surface due
to its consumption by the cathode. In October 1954,
a sudden inspiration led Clark to substitute a less
O2-permeable and electrically insulating polyethy-
lene membrane for cellophane, by mounting a refer-
ence electrode and cathode in electrolyte in a sealed
probe (Figure 3). His invention was presented at a
meeting of the FASEB in April 1956.
Details In a polarographic oxygen electrode, a nega-
tively biased platinum cathode donates electrons to
Sample
H+ permeable
glass
Teflon
or
Glass body silastic
membrane
Sample
 ARTERIAL BLOOD GASES 147

Clark-type oxygen electrode

25 µm polypropylene membrane
Sample

0.1 m KCl electrolyte

10 µm Platinum wire

Solid glass

AgCl reference

Sample
Figure 3 Schema of Clark’s polarographic PO2 electrode, after
cathode size was greatly reduced to avoid ‘stirring’ effect.
Figure 4 The first blood gas analyzer containing three elec-
dissolved oxygen: trodes in a water bath at 371C with tonometer for preparing blood
for calibration of PO2 electrode. Reproduced from Severinghaus
O2 þ 4e
þ 2H2 O ) 4OH
JW (2002) The invention and development of blood gas appa-
ratus. Anaesthesiology 97: 253–256, with permission from
The only major functional change since Clark’s orig- Lippincott Williams & Wilkins.
inal invention has been to reduce the cathode diam-
eter from 2 mm to about 10 mm, requiring far more
sensitive current analysis, which was not available 50
years ago. This almost eliminated the need for the
sample to be rapidly stirred. The electrolyte usually
contains KCl, and may have added agents for vis-
cosity. No separator is needed between cathode and
membrane. The cathode is biased to about
0.65 V
at which all oxygen molecules reaching the cathode
are reduced. Cathode current is a linear function of
the membrane surface PO2 .

Blood Gas Analyzers

In 1958, Severinghaus and Bradley created the first

three-function blood gas analyzer by mounting a
Clark PO2 electrode with a tiny stirring paddle, a
Stow–Severinghaus PCO2 electrode, and a commer-
cial pH electrode in a water bath at 371C (Figure 4).
A small tonometer was included in which blood
could be equilibrated with air or a known gas to
calibrate the Clark electrode. Modern blood gas
analyzers compute many variables from the three
measured values.
Transcutaneous PO2
PaO2 can be estimated transcutaneously using a flat
Clark type PO2 electrode, typically internally heated
to about 431C. Heating causes sufficient dermal vaso-
dilation to raise skin capillary PO2 to nearly equal
arterial PO2 . Heating also raises blood PO2 by about
7% per degree, while skin oxygen consumption re-
duces surface PO2 , these two factors approximately
canceling each other out. No correction factors for
Figure 5 Transcutaneous combined PO2 and PCO2 electrode
monitoring a patient recovering from anesthesia.
temperature or skin metabolism are thus needed. In-
troduced in the mid-1970s, these devices are widely
used on premature and term infants to help control
oxygen therapy and prevent blindness following ret-
inal vascular growth interference (Figure 5).
Transcutaneous PCO2
Arterial PCO2 can also be estimated transcutaneously
using flat CO2 electrodes heated (e.g., to 431C) to
increase skin capillary blood flow. The signal must be
corrected
4.7% per degree to 371C, and reduced
about 4 Torr to compensate for skin metabolism and
electrode surface cooling.
148 ARTERIAL BLOOD GASES

Hemoglobin Oxygen Saturation

Prior to about 1970, this was measured by vacuum
extraction of oxygen from blood, before and after
equilibrating a sample with air.

Multiwavelength Oximetry
Compared with oxygenated blood, desaturated
blood strongly absorbs red light (at about 660 nM
wavelength). At the isobestic point, 805 nM (near
infrared), absorption is unaffected by oxygenation.
Multiwavelength oximeters use the ratio of optical
density of a thin film of hemolyzed blood at red and Figure 6 Pulse oximeter probe taped on fingertip with red and
infrared wavelengths to calculate saturation and infrared LEDs on nail side and a photo diode on the dorsal side.
hemoglobin concentration, with small corrections
for other pigments such as bilirubin, detected at
other wavelengths. A typical laboratory ‘bench’ oxi-
meter using at least five wavelengths can be precise to Photodiode
at least 0.1% saturation. Some oximeters use filters
to select wavelengths while others use more stable
and precisely defined diffusion-grating monochroma-
Finger
tors, avoiding the need for user calibration. Con-
firmatory testing with dyes is recommended. Some
blood gas analyzers include a multiwavelength oxi-
meter (often termed CO-oximeter because it also
measures the fraction of hemoglobin bound to car- Red and infrared LEDs
bon monoxide).

Pulse Oximetry Figure 7 Schema of pulse oximeter probe on a finger.

Light passing through a finger or ear is partly ab-

sorbed by the blood in its path. Arteries expand with
each pulse, absorbing a bit more light. Pulse oxime-
ters measure the amplitude of the pulsatile variation
of light as a fraction of total transmitted red
(e.g., 660 nM) and infrared (e.g., 900–950 nM) light
(Figures 6 and 7). The ratio of these two ratios was
shown by T Aoyagi in 1973 (Nihon Kohden Co,
Tokyo) to be a unique function of arterial oxygen
saturation, theoretically independent of venous or
capillary saturation, or skin color, tissue thickness, or
other pigments.
In the late 1940s, Earl Wood (Mayo Clinic) modi-
fied G Millikan’s 1942 original ear oximeter by add-
ing a pneumatic pressure capsule. Wood showed that
when blood was readmitted to a pressure-blanched
ear, the ratios of the decreases in red and infrared
light passing through the ear were unique functions
of oxygen saturation.
Indications
Blood gas analysis has become so commonplace that
its use is nearly universal in diagnosis during admis-
sion, in emergencies, trauma, intensive care, an-
esthesia, and surgery. It is considered by physicians to
be the most useful and important diagnostic proce-
dure available. Its indications are global and will not
be listed here.
Common Patterns of Results and
Interpretation
Diagnostic Terminology
A pH of less than 7.35 is called acidemia, while that
over 7.45 is termed alkalemia. A PCO2 over 45 Torr
indicates respiratory acidosis or hypercapnia, while
values under 35 (males) or 30 (females) indicate
respiratory alkalosis or hypocapnia. A standard base
excess (SBE) more negative than
5 mM is metabolic
acidosis and over þ 5 mM is metabolic alkalosis.
Presence of compensatory responses to chronic acid–
base respiratory or metabolic imbalances can be pre-
dicted and used in diagnosis (Figure 8).
Normal PO2 at sea level in young adults is 90–
100 mmHg. It falls with age to 60–70 mmHg at age
80. There is no consensus on what PO2 level is de-
fined as ‘hypoxia’. Arterial oxyhemoglobin ‘func-
tional’ saturation (100 x HbO2/[HbO2 þ HHb]) is
normally 97–98% (i.e., 2–3% deoxyhemoglobin,

30
7.7 7.6 7.5
M abolic abnormalities in addition to obtaining an ap-
20
Metabolic SBE (mM)
10
0 AR AR
−10 CR
−20 M and PO2 without separate ion measurements. SBE is
Respiratory Respiratory
alkalosis acidosis
−30
10 20 30 40 50 60 70
Respiratory PaCO2 (Torr)
Figure 8 Acid–base compensation diagram predicting in vivo
compensation for respiratory and metabolic acid–base imbal-
ance. AR and CR, acute and chronic respiratory, respectively; M,
metabolic. Reproduced from Schlichtig R, Grogono AW, and
Severinghaus JW (1998) Human PaCO2 and standard base ex-
cess compensation of blood gas apparatus. Critical Care Med-
icine 26: 1173–1179, with permission from Lippincott Williams &
Wilkins.
HHb). Carboxyhemoglobin or methemoglobin or
other abnormal forms, if present, reduces ‘fractional’
saturation (or % oxyhemoglobin) computed as 100 x
HbO2/total Hb but is not counted in ‘functional’
saturation. The terms ‘hypoxia’ or ‘hypoxemia’ gen-
erally imply that SaO2 is at least 5% lower than ex-
pected (at that age and altitude).
Temperature Correction
Clinicians often ask whether they should instruct the
laboratory to correct blood gas values to patient tem-
perature. In general, this is not necessary. The appro-
priate pH and PCO2 for optimal physiologic function
is the same function of temperature as are the in vitro
temperature correction factors. At 301C in a hypo-
thermic patient, the appropriate pH is 7.4 measured at
371C, or 7.55 corrected to 301C. Animals with a nor-
mal body temperature of 301C have a pH of 7.55.
Fish in Antarctic waters at 01C have a pH of 8.0, as
does normal human blood cooled in vitro to 01C.
Blood at 90% SaO2 with PO2 ¼ 60 Torr will have
PO2 ¼ 30 Torr at 251C, but delivers oxygen at least as
effectively to tissues in hypothermia (as shown by de-
creased tissue lactate). However, physiologists who
wish to study pulmonary gas transport and compare
alveolar and arterial blood gas tension gradients must
correct blood values from the laboratory (at 371C) to
the body temperature under study.
SID or SBE?
The interpretation of acid–base balance divides
clinicians into two ‘schools of thought’. Strong ion
ARTERIAL BLOOD GASES 149
7.4
difference (SID) can identify the causes of many met-
proximation of the degree of plasma metabolic acid–
CR 7.3 base abnormality, provided that all anions and cat-
Metabolic
alkalosis 7.2
ions are measured. This unfortunately is not a meas-
ure of the whole body extracellular fluid acid–base
Metabolic
acidosis 7.1 condition. For that one needs the SBE, which is
7.0 computed from directly measured arterial pH, PCO2 ,
pH
thus a quantitative analysis of imbalance while SID is
80 90 an approximation of imbalance with additional caus-
ative suggestions.
Hydrogen Ion Concentration or pH?
pH is used widely both for convenience and because
chemical activities and potentials are log functions of
concentrations. All animals no matter what their
normal body temperature maintain their pH 0.6 unit
above neutrality, i.e., a ratio of [OH
]/[H þ ] of
about 16 whereas [H þ ] varies by a factor of more
than 4 between 01C (fish) and 401C (hummingbirds).
Buffering is a linear function of pH, an exponential
function of [H þ ] making straight pH lines on acid–
base compensation plots.
Some clinicians prefer to interpret acid–base ab-
normalities using an approximation of Hendersen’s
equation:
Hþ ¼ 24PCO2 =HCO

3
using nM l
1 for H þ , mmHg for PCO2 and mM l
1
for HCO3
. This requires a constant 24 combining
the dissociation constant K, CO2 solubility, equating
carbonic acid with dissolved CO2, and a factor for
the three different units.
Oxygen Dissociation Curve Computations
and Corrections
Blood gas analytic apparatus commonly provides a
computed value of SO2 (oxygen saturation). The ob-
served PO2 is first corrected from observed pH to
pH ¼ 7.4 by
obs
logP7:4 obs
O2 ¼ logPO2
ð0:48ð7:4
pH ÞÞ
At pH ¼ 7.40, 371C, the relationship of SO2 to PO2
is most simply and accurately expressed by
SO2 % ¼ 100ð23; 400ðP3O2 þ 150PO2 Þ
1 þ 1Þ
1
No temperature correction (e.g., to patient tem-
perature) is needed, all measurements being at 371C.
150 ARTERIES AND VEINS
SO2 in a blood sample does not vary with sample
temperature.
State of the Art
Electrodes versus Optical Sensors
Optodes can measure pH, PCO2 and PO2 using dyes,
fluorescence, quenching, and other optically respon-
sive material, permitting the use of extremely small
sensors on optical fiber tips in blood at catheter tips
or inside tissue cells. They rival electrodes in accu-
racy and cost, in particular providing portable and
disposable sensors (e.g., for cardiac bypass oxygena-
tor control, bedside and field blood gas analysis).
See also: Acid–Base Balance. Diffusion of Gases.
Diving. Erythrocytes. High Altitude, Physiology and
Diseases. Oxygen–Hemoglobin Dissociation Curve.
Permeability of the Blood–Gas Barrier. Ventilation:
Control.
ARTERIES AND VEINS
D E deMello, Saint Louis University Health Sciences
Center, St Louis, MO, USA
& 2006 Elsevier Ltd. All rights reserved.
Abstract
The lung’s vasculature is different from that of most other
organs because it has a double arterial supply and a double
venous drainage system. The pulmonary artery which carries
deoxygenated blood to the lungs branches alongside the airways
into conventional and supernumerary arteries before it empties
into the vast capillary network in the alveolar walls where
gas exchange occurs across air–blood barriers. Conventional
and supernumerary pulmonary veins drain oxygenated blood
to the left atrium of the heart. The smaller (intra-acinar) vessels
develop at the same time as do the acini of the lung and a
major component of acinar lung development occurs post-
natally. Alveoli increase from about 20 million at birth to
about 300 million by the time lung growth is complete in
adolescence. Consequently, a large component of intra-acinar
vessels develop postnatally and during this critical growth phase
are susceptible to local influences such as increased blood flow
from intracardiac left to right shunts which can curtail vessel
growth.
Arterial wall structure is composed of endothelial cells that
line the lumen, smooth muscle cells that make up the media, and
fibroblasts that contribute the adventitial fibrous sheath. The
wall structure changes from proximal to distal vessels in the
lung, and alterations in the normal structure may occur during
intrauterine life or postnatally in response to a variety of stimuli.
Altered wall structure results in functional changes reflected in
pulmonary artery pressure and resistance.
Further Reading
Geha DG (1990) Blood gas monitoring. In: Blitt CDK (ed.) Mon-
itoring in Anesthesia and Critical Care Medicine. New York:
Churchill-Livingston.
Nunn JF (1993) Nunn’s Applied Respiratory Physiology, 4th edn.
Oxford: Butterworth-Heinemann.
Schlichtig R, Grogono AW, and Severinghaus JW (1998) Human
PaCO2 and standard base excess compensation for acid-base
imbalance. Critical Care Medicine 26: 1173–1179.
Severinghaus JW (1979) Simple, accurate equations for human
blood O2 dissociation computations. Journal of Applied Phys-
iology 46: 599–602.
Severinghaus JW (2002) The invention and development of blood
gas apparatus. Anaesthesiology 97: 253–256.
Severinghaus JW and Astrup PB (1987) History of Blood Gas
Analysis. International Anesthesiology Clinics, vol. 25(4).
Boston: Little Brown.
Severinghaus JW, Astrup P, and Murray J (1998) Blood gas anal-
ysis and critical care medicine. American Journal of Respiratory
Critical Care Medicine 157: S114–S122.
Severinghaus JW and Bradley AF Jr (1958) Electrodes for blood
PO2 and PCO2 determination. Journal of Applied Physiology
13: 515–520.
Blood vessel assembly begins in primitive mesenchymal cells
that undergo a complex series of steps before the mature vessel
structure and function is attained. These stages in vessel devel-
opment are under the control of a large number of transcrip-
tional and growth factors. The timing and dose of some of these
‘angiogenic’ factors is critical to normal embryonic and fetal
development; absence or even reduced expression of some fac-
tors is lethal for the developing embryo.
Anatomy, Histology, and Structure
Unlike most other organs, the lung, because of its gas
exchange function, has a double arterial supply and
double venous drainage (Figure 1). One of the arte-
rial systems, the pulmonary arterial tree, serves as a
conduit for deoxygenated blood from the body to the
alveoli where it drains into a vast capillary network
within which gas exchange and oxygenation occur.
From the alveoli, oxygenated blood is transported to
the left atrium of the heart via the pulmonary veins.
The other arterial system is the bronchial arterial tree
which serves a nutrient function to the airways and
perihilar structures. The arterial supply to the pleura,
except at the hilar region, is from the pulmonary
artery. For the intrapulmonary structures there are
no bronchial veins, so all intrapulmonary structures
drain to the pulmonary vein, resulting in a small
amount of venous admixture in the left atrium. The
hilar structures, however, drain to true bronchial