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Xenopus oocytes; however, subsequent studies expression/function to reduce secretion/ASL viscosity

showed unimpaired CO2 permeability in AQP1-de- in cystic fibrosis.
ficient erythrocytes, where rapid CO2 transport
occurs by a passive membrane solubility-diffusion See also: Basal Cells. Fluid Balance in the Lung.
mechanism. Measurements of CO2 movement in the
perfused and in vivo mouse lung showed no effect of Further Reading
AQP1 deletion, providing direct evidence against the
role of AQP1 in lung CO2 transport. 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
Aquaporins and Respiratory Disease aquaporin-1 and aquaporin-4 knockout mice. Journal of Clin-
ical Investigation 103: 555–561.
A small number of AQP1-deficient humans have been Borok Z and Verkman AS (2002) Lung edema clearance: 20 years
identified. Although initially reported to have no phe- of progress. Invited review: role of aquaporin water channels in
fluid transport in lung and airways. Journal of Applied Phys-
notype, subsequent studies showed that they mani- iology 93: 2199–2206.
fest a urine concentrating defect that is qualitatively Dobbs L, Gonzalez R, Matthay MA, et al. (1998) Highly water-
similar to that found in AQP1-deficient mice. As permeable type I alveolar epithelial cells confer high water
mentioned above, AQP1-deficient subjects have also permeability between the airspace and vasculature in rat lung.
Proceedings of the National Academy of Sciences, USA 95:
been found to have a small reduction in the increase
in bronchiolar wall thickness following intravenous Folkesson H, Matthay MA, Frigeri A, and Verkman AS (1996)
volume overload compared to normal controls, High transepithelial water permeability in microperfused distal
though other lung phenotypes have not been re- airways: evidence for channel-mediated water transport. Journal
ported. The significance of this observation is unclear. of Clinical Investigation 97: 664–671.
Together with a considerable body of data in King LS, Nielsen S, and Agre P (1996) Aquaporin-1 water channel
protein in lung-ontogeny, steroid-induced expression, and dis-
transgenic mice, the functional studies suggest that tribution in rat. Journal of Clinical Investigation 97: 2183–
aquaporins play at most a minor role in normal lung 2191.
physiology and clinically relevant states of lung in- King LS, Nielsen S, Agre P, and Brown RH (2002) Decreased
jury, with the possible exception of AQP5 in sub- pulmonary vascular permeability in aquaporin-1-null humans.
mucosal fluid secretion. It remains unresolved why Proceedings of the National Academy of Sciences USA 99:
aquaporins are expressed at multiple sites of fluid Krane CM, Fortner CN, Hand AR, et al. (2001) Aquaporin-5 de-
movement in the lung/airways, and why the expres- ficient mouse lungs are hyperresponsive to cholinergic stimula-
sion of lung aquaporins appears to be altered in states tion. Proceedings of the National Academy of Sciences, USA 98:
of stress. When available, nontoxic aquaporin-selec- 14114–14119.
Ma T, Fukuda N, Song Y, Matthay MA, and Verkman AS (2000)
tive inhibitors will be useful to examine effects of
Lung fluid transport in aquaporin-5 knockout mice. Journal of
acute aquaporin inhibition, which may reveal lung/ Clinical Investigation 105: 93–100.
airway phenotypes that might not be manifest in mice Saadoun S, Papadopoulos M, Hara-Chikuma M, and Verkman AS
or humans with chronic aquaporin deficiency. If sig- (2005) Targeted AQP1 gene deletion impairs angiogenesis and
nificant aquaporin-dependent phenotypes are found, cell migration. Nature 434: 786–792.
then pharmacological modulation of aquaporin func- Song Y and Verkman AS (2001) Aquaporin-5 dependent fluid se-
cretion in airway submucosal glands. Journal of Biological
tion may have clinical applications, such as AQP5 Chemistry 276: 41288–41292.
inhibition in reducing glandular fluid secretions in Verkman AS (2002) Physiological importance of aquaporin water
allergic and infectious rhinitis, or increasing AQP5 channels. Annals of Medicine 34: 192–200.


J W Severinghaus, UCSF, San Francisco, CA, USA following inventions by R Stow (CO2) and L Clark (PO2) both
dating from 1954. From these outputs, internal computers cal-
& 2006 Elsevier Ltd. All rights reserved.
culate O2 saturation, base excess, bicarbonate, and other derived
variables such as the compensation by the body for acid–base
Abstract abnormalities. Arterial PO2 and PCO2 can be approximated using
heated skin surface ‘transcutaneous’ electrodes, which are
Blood gas analyzers consist of three electrodes measuring pH, commonly used in premature infants and nurseries. Hemoglo-
PCO2 , and PO2 at 371C. They were introduced in about 1960 bin oxygen saturation, SO2%, is also directly measured by

multiwavelength blood oximeters. Arterial SO2 is approximated Henderson–Hasselbalch (HH) equation:

by pulse oximeters, which detect the arterial pulsatile variations
in red and infrared light penetrating a finger, ear, or other tissue, pH ¼ pK0 þ log½HCO
a method invented by T Aoyagi in Tokyo in 1973 that became 3 =SPCO2 
commercially available in 1983. Interpretation of blood gases
and acid–base balance is briefly discussed. Figures include In plasma, pK0 ¼ 6.1, the effective dissociation
schema of the three electrodes, a pulse oximeter probe, an constant of H2CO3 (carbonic acid), calculated as S
acid–base compensation diagram, and photographs of the first PCO2 . S is CO2 solubility, 0.031 mM l  1 Torr  1.
three-function blood gas analyzer, a combined PO2 PCO2 trans-
HCO3 is plasma bicarbonate content calculated as
cutaneous electrode in use on a child, and a pulse oximeter probe
on a finger. plasma [CO2 content – SPCO2 ].

Introduction Electrodes
pH Electrode
Arterial blood gas analyzers directly measure pH,
PCO2 and PO2 , (mmHg or Torr) and calculate stand- In 1905, Max Cremer noted that hydrogen ions per-
ard base excess (SBE), bicarbonate (HCO3 ), oxygen meated some kinds of very thin glass, developing
saturation (SO2), and other variables useful in diag- electrical potential gradients across the glass. Fritz
nosis and clinical management of patients in emer- Haber and Z Klemensiewicz made the first glass pH
gencies, anesthesia, surgery, recovery, and intensive electrode in 1909. Its potential was a linear function
care. These tests were rarely done until the 1950s of pH, not H þ ion concentration. In 1925, the first
when electrodes were invented and developed. Un- glass cup-shaped blood pH electrode was produced
derstanding of acid–base and blood gas theory de- by Phyllis T Courage. By 1933, capillary blood pH
pended on discoveries in physical chemistry. electrodes were being made commercially. Blood pH
was corrected to 371C with the Rosenthal factor
Ionic Theory (  0.0147 1C  1) until thermostatted blood pH elec-
Electrochemistry and physical chemistry of solutions trodes became available in the 1950s. A pH and ref-
of acids, alkalis, metals, and salts were transfor- erence electrode is schematically shown in Figure 1.
med from empiricism to theory by the 1884 thesis
of Svante Arrhenius in Uppsala, Sweden. Wilhelm Details Special glass compositions permit hydrogen
Ostwald then used a platinum electrode to measure ions to diffuse through imperfectly annealed sub-
hydrogen ion strength electrically. In 1893, microscopic cracks, probably exchanging loci with
Ostwald’s student Walther Nernst applied the long- loosely bound alkali cations, especially lithium. Some
established laws of gases to ions in solution to cal- pH electrodes are sensitive to very high Na þ con-
culate the electrical potential of batteries or cells. centrations. At 371C, the electromotive force (EMF)
across the glass measured with reference electrodes
Buffers (usually silver–silver chloride) is 61.5 mV per pH unit
change (a 10-fold change in H þ ion concentration).
Shortly after 1900, Lawrence J Henderson at Har-
vard adapted the mass action law to relate [H þ ] to Sample
PCO2 and HCO3 :
K ¼ ½Hþ ½HCO
3 =H2 CO3

Glass body
He demonstrated how respiration could buffer met-
abolic acids by reducing PCO2 . The kidneys can also
AgCl internal reference
change blood and extracellular fluid buffer base
to partially normalize pH in respiratory acidosis or
alkalosis. H+ permeable

Origin of pH Liquid junction

Saturated KCl
In order to define H þ ion concentrations such as AgCl reference
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 Sample
(or activity). In 1915, K A Hasselbalch converted Figure 1 Schema of a blood pH electrode with a liquid junction
Henderson’s equation to log form, later dubbed the to a reference electrode in a thermostatted cuvette.

For use in blood, the reference electrode usually con- Details An internal, nearly flat, glass pH electrode
tacts blood via a liquid junction containing saturated is separated from the sample by a membrane perme-
KCl. Rapid diffusion of K þ into red cells causes an able to CO2 but not ions (e.g., Teflon or silastic).
often-ignored error of  0.01 pH at the liquid junc- Under the membrane, a spacer (e.g., lens-cleaning
tion when calibration is done with aqueous buffers. tissue paper) holds a film of electrolyte containing
about 10 mM NaHCO3 and usually 0.1 M salt or
PCO2 Measurement KCl. Thermostatted to 37oC, the output signal is a
Until the worldwide polio epidemics of 1950–52, log function of PCO2 , about 30 mV per decade in
PCO2 was measured by the HH equation. This re- distilled water (Stow’s design), doubling to 61 mV
quired measuring plasma CO2 content by acidifica- per decade with bicarbonate electrolyte.
tion and extraction in a manometric Van Slyke
apparatus and measuring pH and correcting it to Oxygen Electrode
371C. In Copenhagen’s communicable disease hos-
pital in 1950–51, sometimes up to 100 patients at a In 1950, Leland Clark at Antioch College, Ohio used
time were manually ventilated by volunteers using a perfused isolated liver to study steroid metabolism.
bag and mask with O2. The laboratory director Poul He needed oxygenated blood so he built a bubble
Astrup, needing a faster analytic method than the oxygenator and discovered how to defoam the blood
HH equation, devised a new simple method. He using silicone oil on glass wool. The journal Science
measured pH before and after equilibrating the sam- rejected his paper on the basis that he hadn’t meas-
ple with known PCO2 . He then computed patient ured the PO2 in the oxygenated blood; to this end,
PCO2 by extrapolation. His method became the Clark invented a polarographic oxygen electrode. He
standard for the rest of the decade. covered a platinum disc cathode sealed in glass with
cellophane to keep blood protein from poisoning the
PCO2 Electrode cathode. It served his purpose but was not accurate,
requiring very high flow past the sensor due to the
At Ohio State University in 1954, while also trying to
depletion of oxygen at the membrane surface due
resolve the polio problem, Richard Stow invented a
to its consumption by the cathode. In October 1954,
PCO2 electrode. He covered a glass bulb-shaped pH
a sudden inspiration led Clark to substitute a less
electrode with a rubber glove (through which CO2
O2-permeable and electrically insulating polyethy-
can diffuse but H þ cannot), over a film of distilled
lene membrane for cellophane, by mounting a refer-
water. However, Stow’s electrode drifted because
ence electrode and cathode in electrolyte in a sealed
various cations in pH glass altered the distilled water
probe (Figure 3). His invention was presented at a
pH. This electrode was stabilized by John Severing-
meeting of the FASEB in April 1956.
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 Details In a polarographic oxygen electrode, a nega-
electrode is illustrated in Figure 2. tively biased platinum cathode donates electrons to

Stow–Severinghaus PCO2 electrode


AgCl external
reference electrode

AgCl internal reference

H+ permeable
0.1M KCl + 0.01M KHCO3 Glass body silastic
in paper spacer
Figure 2 Schema of a blood PCO2 electrode with Teflon CO2 permeable membrane and spacer to contain electrolyte for pH meas-

Clark-type oxygen electrode

25 µm polypropylene membrane

0.1 m KCl electrolyte

10 µm Platinum wire

Solid glass

AgCl reference

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

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-
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 be the most useful and important diagnostic proce-
each pulse, absorbing a bit more light. Pulse oxime- dure available. Its indications are global and will not
ters measure the amplitude of the pulsatile variation be listed here.
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 Common Patterns of Results and
shown by T Aoyagi in 1973 (Nihon Kohden Co, Interpretation
Tokyo) to be a unique function of arterial oxygen
Diagnostic Terminology
saturation, theoretically independent of venous or
capillary saturation, or skin color, tissue thickness, or A pH of less than 7.35 is called acidemia, while that
other pigments. over 7.45 is termed alkalemia. A PCO2 over 45 Torr
In the late 1940s, Earl Wood (Mayo Clinic) modi- indicates respiratory acidosis or hypercapnia, while
fied G Millikan’s 1942 original ear oximeter by add- values under 35 (males) or 30 (females) indicate
ing a pneumatic pressure capsule. Wood showed that respiratory alkalosis or hypocapnia. A standard base
when blood was readmitted to a pressure-blanched excess (SBE) more negative than  5 mM is metabolic
ear, the ratios of the decreases in red and infrared acidosis and over þ 5 mM is metabolic alkalosis.
light passing through the ear were unique functions Presence of compensatory responses to chronic acid–
of oxygen saturation. 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
Blood gas analysis has become so commonplace that 80. There is no consensus on what PO2 level is de-
its use is nearly universal in diagnosis during admis- fined as ‘hypoxia’. Arterial oxyhemoglobin ‘func-
sion, in emergencies, trauma, intensive care, an- tional’ saturation (100 x HbO2/[HbO2 þ HHb]) is
esthesia, and surgery. It is considered by physicians to normally 97–98% (i.e., 2–3% deoxyhemoglobin,

7.7 7.6 7.5 7.4
difference (SID) can identify the causes of many met-
M abolic abnormalities in addition to obtaining an ap-
20 proximation of the degree of plasma metabolic acid–
Metabolic SBE (mM)

10 CR 7.3 base abnormality, provided that all anions and cat-

alkalosis 7.2
ions are measured. This unfortunately is not a meas-
0 AR AR ure of the whole body extracellular fluid acid–base
acidosis 7.1 condition. For that one needs the SBE, which is
−10 CR 7.0 computed from directly measured arterial pH, PCO2 ,
−20 M and PO2 without separate ion measurements. SBE is
Respiratory Respiratory
alkalosis acidosis thus a quantitative analysis of imbalance while SID is
10 20 30 40 50 60 70 80 90 an approximation of imbalance with additional caus-
Respiratory PaCO2 (Torr) ative suggestions.

Figure 8 Acid–base compensation diagram predicting in vivo Hydrogen Ion Concentration or pH?
compensation for respiratory and metabolic acid–base imbal-
ance. AR and CR, acute and chronic respiratory, respectively; M, pH is used widely both for convenience and because
metabolic. Reproduced from Schlichtig R, Grogono AW, and chemical activities and potentials are log functions of
Severinghaus JW (1998) Human PaCO2 and standard base ex- concentrations. All animals no matter what their
cess compensation of blood gas apparatus. Critical Care Med-
icine 26: 1173–1179, with permission from Lippincott Williams &
normal body temperature maintain their pH 0.6 unit
Wilkins. 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
HHb). Carboxyhemoglobin or methemoglobin or
function of [H þ ] making straight pH lines on acid–
other abnormal forms, if present, reduces ‘fractional’
base compensation plots.
saturation (or % oxyhemoglobin) computed as 100 x
Some clinicians prefer to interpret acid–base ab-
HbO2/total Hb but is not counted in ‘functional’
normalities using an approximation of Hendersen’s
saturation. The terms ‘hypoxia’ or ‘hypoxemia’ gen-
erally imply that SaO2 is at least 5% lower than ex-
pected (at that age and altitude). Hþ ¼ 24PCO2 =HCO

Temperature Correction using nM l  1 for H þ , mmHg for PCO2 and mM l  1

Clinicians often ask whether they should instruct the for HCO3 . This requires a constant 24 combining
laboratory to correct blood gas values to patient tem- the dissociation constant K, CO2 solubility, equating
perature. In general, this is not necessary. The appro- carbonic acid with dissolved CO2, and a factor for
priate pH and PCO2 for optimal physiologic function the three different units.
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 Oxygen Dissociation Curve Computations
371C, or 7.55 corrected to 301C. Animals with a nor- and Corrections
mal body temperature of 301C have a pH of 7.55. Blood gas analytic apparatus commonly provides a
Fish in Antarctic waters at 01C have a pH of 8.0, as computed value of SO2 (oxygen saturation). The ob-
does normal human blood cooled in vitro to 01C. served PO2 is first corrected from observed pH to
Blood at 90% SaO2 with PO2 ¼ 60 Torr will have pH ¼ 7.4 by
PO2 ¼ 30 Torr at 251C, but delivers oxygen at least as
effectively to tissues in hypothermia (as shown by de- obs
logP7:4 obs
O2 ¼ logPO2  ð0:48ð7:4  pH ÞÞ
creased tissue lactate). However, physiologists who
wish to study pulmonary gas transport and compare
alveolar and arterial blood gas tension gradients must At pH ¼ 7.40, 371C, the relationship of SO2 to PO2
correct blood values from the laboratory (at 371C) to is most simply and accurately expressed by
the body temperature under study.
SO2 % ¼ 100ð23; 400ðP3O2 þ 150PO2 Þ1 þ 1Þ1

The interpretation of acid–base balance divides No temperature correction (e.g., to patient tem-
clinicians into two ‘schools of thought’. Strong ion perature) is needed, all measurements being at 371C.

SO2 in a blood sample does not vary with sample Further Reading
Geha DG (1990) Blood gas monitoring. In: Blitt CDK (ed.) Mon-
itoring in Anesthesia and Critical Care Medicine. New York:
State of the Art Churchill-Livingston.
Nunn JF (1993) Nunn’s Applied Respiratory Physiology, 4th edn.
Electrodes versus Optical Sensors Oxford: Butterworth-Heinemann.
Schlichtig R, Grogono AW, and Severinghaus JW (1998) Human
Optodes can measure pH, PCO2 and PO2 using dyes, PaCO2 and standard base excess compensation for acid-base
fluorescence, quenching, and other optically respon- imbalance. Critical Care Medicine 26: 1173–1179.
sive material, permitting the use of extremely small Severinghaus JW (1979) Simple, accurate equations for human
blood O2 dissociation computations. Journal of Applied Phys-
sensors on optical fiber tips in blood at catheter tips
iology 46: 599–602.
or inside tissue cells. They rival electrodes in accu- Severinghaus JW (2002) The invention and development of blood
racy and cost, in particular providing portable and gas apparatus. Anaesthesiology 97: 253–256.
disposable sensors (e.g., for cardiac bypass oxygena- Severinghaus JW and Astrup PB (1987) History of Blood Gas
tor control, bedside and field blood gas analysis). Analysis. International Anesthesiology Clinics, vol. 25(4).
Boston: Little Brown.
Severinghaus JW, Astrup P, and Murray J (1998) Blood gas anal-
See also: Acid–Base Balance. Diffusion of Gases. ysis and critical care medicine. American Journal of Respiratory
Diving. Erythrocytes. High Altitude, Physiology and Critical Care Medicine 157: S114–S122.
Diseases. Oxygen–Hemoglobin Dissociation Curve. Severinghaus JW and Bradley AF Jr (1958) Electrodes for blood
Permeability of the Blood–Gas Barrier. Ventilation: PO2 and PCO2 determination. Journal of Applied Physiology
Control. 13: 515–520.


D E deMello, Saint Louis University Health Sciences Blood vessel assembly begins in primitive mesenchymal cells
Center, St Louis, MO, USA that undergo a complex series of steps before the mature vessel
structure and function is attained. These stages in vessel devel-
& 2006 Elsevier Ltd. All rights reserved. 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
Abstract development; absence or even reduced expression of some fac-
The lung’s vasculature is different from that of most other tors is lethal for the developing embryo.
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 Anatomy, Histology, and Structure
into conventional and supernumerary arteries before it empties
into the vast capillary network in the alveolar walls where Unlike most other organs, the lung, because of its gas
gas exchange occurs across air–blood barriers. Conventional exchange function, has a double arterial supply and
and supernumerary pulmonary veins drain oxygenated blood double venous drainage (Figure 1). One of the arte-
to the left atrium of the heart. The smaller (intra-acinar) vessels rial systems, the pulmonary arterial tree, serves as a
develop at the same time as do the acini of the lung and a
major component of acinar lung development occurs post-
conduit for deoxygenated blood from the body to the
natally. Alveoli increase from about 20 million at birth to alveoli where it drains into a vast capillary network
about 300 million by the time lung growth is complete in within which gas exchange and oxygenation occur.
adolescence. Consequently, a large component of intra-acinar From the alveoli, oxygenated blood is transported to
vessels develop postnatally and during this critical growth phase the left atrium of the heart via the pulmonary veins.
are susceptible to local influences such as increased blood flow
from intracardiac left to right shunts which can curtail vessel
The other arterial system is the bronchial arterial tree
growth. which serves a nutrient function to the airways and
Arterial wall structure is composed of endothelial cells that perihilar structures. The arterial supply to the pleura,
line the lumen, smooth muscle cells that make up the media, and except at the hilar region, is from the pulmonary
fibroblasts that contribute the adventitial fibrous sheath. The artery. For the intrapulmonary structures there are
wall structure changes from proximal to distal vessels in the
lung, and alterations in the normal structure may occur during
no bronchial veins, so all intrapulmonary structures
intrauterine life or postnatally in response to a variety of stimuli. drain to the pulmonary vein, resulting in a small
Altered wall structure results in functional changes reflected in amount of venous admixture in the left atrium. The
pulmonary artery pressure and resistance. hilar structures, however, drain to true bronchial

Related Interests