Oxygen

THE OXYGEN CASCADE

• The P o 2 of dry air at sea level is 21.2 kPa (159 mmHg).
• Oxygen moves down a partial pressure gradient from air,
through the respiratory tract, the alveolar gas, the arterial
blood, the systemic capillaries, the tissues and the cell.

• It fi nally reaches its lowest level in the mitochondria where

it is consumed ( Figure 11.1 ).

• At this point, the P o 2 is probably within the range 0.5 – 3

kPa (3.8– 22.5 mmHg), varying from one tissue to another,
from one cell to another, and from one region of a cell to
another.

• The steps by which the P o 2 decreases from air to the

mitochondria are known as the oxygen cascade
 DILUTION OF INSPIRED OXYGEN BY
WATER VAPOUR
• The normally quoted value for the concentration
of atmospheric oxygen (20.94% or 0.2094
fractional concentration) indicates the
concentration of oxygen in dry gas.

• As gas is inhaled through the respiratory tract, it

becomes humidifi ed at body temperature and
the added water vapour dilutes the oxygen and
so reduces the P o 2 below its level in the
ambient air.
• When dry gas at normal barometric pressure
becomes fully saturated with water vapour at
37 ° C, 100 volumes of the dry gas take up
about 6 volumes of water vapour, giving a
total gas volume of 106 units but containing
the same number of molecules of oxygen.
• The Po2 is thus reduced by the fraction 6/106.
It follows from Boyle’s law that P o 2 after
humidification is indicated by the following
expression:
• (the quantity in parentheses is known as the dry
barometric pressure).
• Therefore the effective P o 2 of inspired air at a
body temperature of 37 ° C is:
• 0.2094 x (101.3 – 6.3 ) = 0.2094 x 95
= 19.9 kPa

• 0.2094x(760 – 47) = 0.2094 x 713

= 149 mmHg
 PRIMARY FACTORS INFLUENCING
ALVEOLAR OXYGEN TENSION
Dry barometric pressure: If other factors
remain constant, the alveolar P o 2 will be
directly proportional to the dry barometric
pressure.

• Thus with increasing altitude, alveolar P o 2

falls progressively to become zero at 19
kilometres where the actual barometric
pressure equals the saturated vapour pressure
of water at body temperature.
• The effect of increased pressure is complex,
for example, a pressure of 10 atmospheres
(absolute) increases the alveolar P o 2 by a
factor of about 15 if other factors remain
constant

• Inspired oxygen concentration: The alveolar P

o2 will be raised or lowered by an amount
equal to the change in the inspired gas P o 2 ,
provided that other factors remain constant.
• An increase in the inspired oxygen concentration
from 21% to 30% will result in improvement of
alveolar P o 2 by8.5 kPa (64 mmHg).

• This will be of great importance if, for example,

hypoventilation while breathing air has reduced
the alveolar P o 2 to 4 kPa (30 mmHg).

• Oxygen enrichment of inspired gas to 30% will

then increase the alveolar P o 2 to 12.5 kPa (94
mmHg), which is almost within the normal range.
Oxygen consumption: Oxygen consumption is raised
by exercise but is often well above basal in a patient
supposedly ‘ at rest ’.

• Oxygen consumption is substantially increased

with sepsis, thyrotoxicosis or convulsions, the first
of which may lead to difficulties with weaning
patients from artificial ventilation.

• Oxygen consumption is reduced with general

anaesthesia, hypothyroidism or hypothermia, the
last of which causes a marked reduction in
oxygen consumption with values of about 50% of
normal at 31 ° C.
• Alveolar ventilation: As ventilation is increased,
the alveolar P o 2 rise asymptomatically towards
(but never reaches) the P o 2 of the inspired gas.

• The ventilation above the normal level have

comparatively little effect on alveolar P o 2 .

• In contrast, changes in ventilation below the

normal level may have a very marked effect.

• At very low levels of ventilation, the alveolar

ventilation becomes critical and small changes
may precipitate severe hypoxia.
SECONDARY FACTORS INFLUENCING
ALVEOLAR OXYGEN TENSION
 Cardiac output
• If other factors remain constant, a sudden
reduction in cardiac output will temporarily
increase the alveolar P o 2 , because less blood
passes through the lungs to remove oxygen from
the alveolar gas.

• However, the reduced cardiac output also causes

increased oxygen extraction in the tissues.

• In the long term, cardiac output does not directly

influence the alveolar P o 2.
The ‘ concentration ’ ,third gas or Fink
effect.
• The alveolar P o 2 is influenced during
exchanges of large quantities of soluble gases
such as nitrous oxide.

• During the early part of the administration of

nitrous oxide, large quantities of the more
soluble gas replace smaller quantities of the
less soluble nitrogen previously dissolved in
body fluids.
• There is thus a net transfer of ‘ inert’ gas from the
alveoli into the body, causing a temporary increase in
the alveolar concentration of both oxygen and
carbon dioxide, which will thus temporarily exert a
higher partial pressure than would otherwise be
expected.

• During recovery from nitrous oxide anaesthesia,

large quantities of nitrous oxide leave the body to be
replaced with smaller quantities of nitrogen.
• There is thus a net outpouring of ‘ inert ’ gas from the
body into the alveoli, causing dilution of oxygen and
carbon dioxide, both of which will temporarily exert a
lower partial pressure than would otherwise be
expected.

• There may then be temporary hypoxia.

• This effect last only a few minutes and hypoxia can easily
be avoided by small increases in the inspired oxygen
concentration when nitrous oxide administration is
stopped.
THE ALVEOLAR/ARTERIAL P O 2
DIFFERENCE
• In the healthy young adult breathing air, the
alveolar/arterial P o 2 difference does not exceed
2 kPa (15 mmHg) but it may rise to above 5 kPa
(37.5 mmHg) in aged but healthy subjects.

• These values may be exceeded in a patient with

any lung disease that causes shunting or
mismatching of ventilation to perfusion.

• An increased alveolar/ arterial P o 2 difference is

the commonest cause of arterial hypoxaemia.
FACTORS INFLUENCING THE MAGNITUDE
OF THE ALVEOLAR/ARTERIAL P O 2
DIFFERENCE
 The magnitude of the venous
admixture
• It increases the alveolar/arterial P o 2
difference with direct proportionality for small
shunts, although this is lost with larger shunts.
 V/Q scatter
• The scatter in ventilation/perfusion ratios
produces an alveolar/arterial P o 2 difference for
the following reasons:
1. More blood flows through the underventilated
overperfused alveoli, and the mixed arterial
blood is therefore poorly-oxygenated blood
from areas of low V/Q ratio.
• The smaller amount of blood flowing through
areas of high V/Q ratio cannot compensate for
blood from alveoli with a low V/Q ratio.
• 2. Due to the bend in the dissociation curve
around a P o 2 of 8 kPa the fall in saturation of
blood from areas of low V/Q ratio tends to be
greater than the rise in saturation of blood
from areas of correspondingly high V/Q.
 The actual alveolar PO 2
• It has a profound but complex and non-linear effect
on the alveolar/arterial P o 2 gradient.
• The alveolar/arterial oxygen content difference for a
given shunt is uninfluenced by the alveolar P o 2 and
the effect on the partial pressure difference arises
entirely in conversion from content to partial
pressure.
• For example, a loss of 1 ml per 100 ml of oxygen
from blood with a P o 2 of 93 kPa (700 mmHg)
causes a fall of P o 2 of about 43 kPa (325
mmHg), most of the oxygen being lost from
physical solution.
• However, if the initial P o 2 were 13 kPa (100
mmHg), a loss of 1 ml per 100 ml would cause a
fall of P o 2 of only 4.6 kPa (35 mmHg), most of
the oxygen being lost from combination with
haemoglobin.
• If the alveolar P o 2 is reduced (e.g. by
underventilation), the alveolar/arterial P o 2
gradient will also be diminished if other
factors remain the same. The arterial P o 2
thus falls less than the alveolar P o 2 .
 Cardiac output
• According to Fick relationship (a reduced cardiac
output per se must increase the arterial/mixed
venous oxygen content difference if the oxygen
consumption remains the same.

• This means that the shunted blood will be more

desaturated, and will therefore cause a greater
decrease in the arterial oxygen level than would
less desaturated blood flowing through a shunt of
the same magnitude.
• So there is inverse relationship between the
cardiac output and the alveolar/arterial oxygen
content difference if the venous admixture is
constant.

• However, when the content difference is

converted to partial pressure difference, the
relationship to cardiac output is no longer truly
inverse, but assumes a complex non-linear.