622 SECTION VIIRespiratory Physiology
because all that can be accomplished in this way is an increase
in the amount of dissolved O 2 in the arterial blood. This is also
true in hypoxic hypoxia when it is due to shunting of unoxy-
genated venous blood past the lungs. In other forms of hy-
poxic hypoxia, O 2 is of great benefit. Treatment regimens that
deliver less than 100% O 2 are of value both acutely and chron-
ically, and administration of O 2 24 h/d for 2 y in this fashion
has been shown to significantly decrease the mortality of
chronic obstructive pulmonary disease. O 2 toxicity and thera-
py are discussed in Clinical Box 36–5.
HYPERCAPNIA & HYPOCAPNIA
HYPERCAPNIA
Retention of CO 2 in the body (hypercapnia) initially stimu-
lates respiration. Retention of larger amounts produces symp-
toms due to depression of the central nervous system:
confusion, diminished sensory acuity, and, eventually, coma
with respiratory depression and death. In patients with these
symptoms, the PCO 2 is markedly elevated, severe respiratory
acidosis is present, and the plasma HCO 3 – may exceed 40
mEq/L. Large amounts of HCO 3 – are excreted, but more
HCO 3 – is reabsorbed, raising the plasma HCO 3 – and partially
compensating for the acidosis.
CO 2 is so much more soluble than O 2 that hypercapnia is
rarely a problem in patients with pulmonary fibrosis. How-
ever, it does occur in ventilation–perfusion inequality and
when for any reason alveolar ventilation is inadequate in the
various forms of pump failure. It is exacerbated when CO 2
production is increased. For example, in febrile patients
there is a 13% increase in CO 2 production for each 1°C rise
in temperature, and a high carbohydrate intake increases
CO 2 production because of the increase in the respiratory
quotient. Normally, alveolar ventilation increases and the
extra CO 2 is expired, but it accumulates when ventilation is
compromised.CLINICAL BOX 36–5
Administration of Oxygen & Its Potential Toxicity
It is interesting that while O 2 is necessary for life in aerobic or-
ganisms, it is also toxic. Indeed, 100% O 2 has been demon-
strated to exert toxic effects not only in animals but also in bac-
teria, fungi, cultured animal cells, and plants. The toxicity seems
to be due to the production of reactive oxygen species includ-
ing superoxide anion (O 2 – ) and H 2 O 2. When 80–100% O 2 is ad-
ministered to humans for periods of 8 h or more, the respiratory
passages become irritated, causing substernal distress, nasal
congestion, sore throat, and coughing.with which these symptoms develop is proportional to the
pressure at which the O 2 is administered; for example, at 4
atmospheres, symptoms develop in half the subjects in 30
min, whereas at 6 atmospheres, convulsions develop in a few
minutes.
On the other hand, exposure to 100% O 2 at 2 to 3 atmos-
pheres can increase dissolved O 2 in arterial blood to the point
that arterial O 2 tension is greater than 2000 mm Hg and tis-
sue O 2 tension is 400 mm Hg. If exposure is limited to 5 h or
less at these pressures, O 2 toxicity is not a problem. There-
fore, hyperbaric O 2 therapy in closed tanks is used to treat
diseases in which improved oxygenation of tissues cannot be
achieved in other ways. It is of demonstrated value in carbon
monoxide poisoning, radiation-induced tissue injury, gas
gangrene, very severe blood loss anemia, diabetic leg ulcers
and other wounds that are slow to heal, and rescue of skin
flaps and grafts in which the circulation is marginal. It is also
the primary treatment for decompression sickness and air
embolism.
In hypercapnic patients in severe pulmonary failure, the CO 2
level may be so high that it depresses rather than stimulates
respiration. Some of these patients keep breathing only be-
cause the carotid and aortic chemoreceptors drive the respira-
tory center. If the hypoxic drive is withdrawn by administering
O 2 , breathing may stop. During the resultant apnea, the arterial
PO 2 drops but breathing may not start again, as PCO 2 further
depresses the respiratory center. Therefore, O 2 therapy in this
situation must be started with care.Some infants treated with O 2 for respiratory distress syn-
drome develop a chronic condition characterized by lung cysts
and densities (bronchopulmonary dysplasia). This syndrome
may be a manifestation of O 2 toxicity. Another complication in
these infants is retinopathy of prematurity (retrolental fi-
broplasia), the formation of opaque vascular tissue in the eyes,
which can lead to serious visual defects. The retinal receptors
mature from the center to the periphery of the retina, and they
use considerable O 2. This causes the retina to become vascular-
ized in an orderly fashion. Oxygen treatment before maturation
is complete provides the needed O 2 to the photoreceptors,
and consequently the normal vascular pattern fails to develop.
Evidence indicates that this condition can be prevented or
ameliorated by treatment with vitamin E, which exerts an anti-
oxidant effect, and, in animals, by growth hormone inhibitors.
Administration of 100% O 2 at increased pressure acceler-
ates the onset of O 2 toxicity, with the production not only of
tracheobronchial irritation but also of muscle twitching, ring-
ing in the ears, dizziness, convulsions, and coma. The speed