Carriage Of Oxygen
At rest, a man consumes about 250
mL oxygen/min, which may rise to more than 4000 mL/min in exercise if he is
very fit Oxygen diffuses from alveolus to blood until equilibrium is reached
when pulmonary capillary Po2 equals alveolar Po2.
The solubility of oxygen in blood is low - 0.000225 mL oxygen per mL of
blood per kPa (0.00003 mL/mL/mmHg) - so that at a normal arterial Po2
of 13.3 kPa (100 mmHg) there is only 3 mL dissolved in each litre of blood. The
main function of the red blood cell pigment, haemoglobin, the key
features of whose structure is shown in Fig. 8a, is to carry the large
quantities of oxygen needed by the tissues.
Each gram of haemoglobin combines
with up to 1.34 mL oxygen, so with a haemoglobin concentration, [Hb], of 150
g/L, blood contains a maximum of 200 mL/L oxygen bound to haemoglobin. This is
known as the oxygen capacity, which varies with [Hb]. The actual amount
of oxygen bound also depends on the Po2. The percentage of
the available binding sites bound to oxygen is known as the oxygen
saturation.
Oxygen saturation:
Amount of oxygen bound to
haemoglobin (mL/L)
Oxygen capacity (mL/L) ×
100%
The oxygen content of the blood
(mL/L) equals the sum of haemoglobin-bound oxygen and the small amount of
dissolved oxy- gen. The rate of rise of oxygen content with increasing partial
pressure depends on the number of free haemoglobin-binding sites remaining and
their affinity for oxygen. As each
oxygen molecule binds in turn to the four haem groups, the quaternary structure
alters and the affinity of
the remaining binding sites for oxygen increases. This cooperative binding increases
the steepness of the oxygen-haemoglobin dissociation curve in the middle
(Fig. 8b), but the curve flatten again at partial pressures above about 8 kPa
(60 mmHg) because there are few unfille binding sites remaining. In arterial
blood, Po2 is normally about 13 kPa (100 mmHg), oxygen
saturation about 97%, and, with a normal [Hb], an oxygen content of about 200
mL/L. Rises or modest falls in Po2 from 13 kPa (100 mmHg),
for example during hyperventilation or mild hypoventilation, cause little
change in the arterial oxygen content, as the dissociation curve is fla in this
region. More severe reductions in Po2, to levels in the steep
region (<8 kPa, 60 mmHg), are associated with significan reductions
in oxygen saturation and content. Consequently, breathing oxygen-enriched air
may significantl raise arterial oxygen content and hence exercise capacity at
high altitude and in patients with chronic hypoxic respiratory disease, but has
little effect on a healthy person at sea level.
Low Po2 in
tissue capillaries causes oxygen release from haemoglobin, whereas the high Po2
in pulmonary capillaries causes oxygen binding. The affinity of haemoglobin for oxygen, and hence the
position of the dissociation curve, varies with local conditions. A reduced
oxygen affinity, shown by a right shift in the curve, is caused by a fall in
pH, a rise in Pco2 (the Bohr effect) or increased
temperature (Fig. 8b). These changes occur in metabolically active tissues such
as exercising muscle and encourage oxygen release. In the lungs, oxygen uptake
is aided by the increasing affinity
of haemoglobin for oxygen, caused by falling Pco2 and
temperature and increased pH and reflecte by a left shift of the curve. The Po2
at which the haemoglobin is 50% saturated is known as the P50.
Under normal arterial conditions (pH = 7.4, Pco2 = 5.3 kPa or
40 mmHg, temperature = 37◦C) P50 = 3.5 kPa (26.3 mmHg); right
shifts raise the P50 and left shifts lower it. A rise in the concentration of 2,3-di(or
bi)phosphoglycerate (2,3-DPG), which is a by-product of glycolysis in red
cells, also causes a right shift. A rise in 2,3-DPG occurs in anaemia, causing
a modest increase in P50. Blood bank storage causes
progressive depletion of 2,3-DPG and an undesirable left shift, but this can be
minimized by storing the blood with citrate-phosphate-dextrose.
Anaemia and carbon monoxide poisoning In anaemia, at any given Po2, the oxygen content
is reduced because of the reduced concentration of binding sites. Figure 8c
shows the dissociation curve for normal blood and for blood with [Hb] = 75g/L.
Alveolar and arterial Po2 is normal in anaemia and therefore
arterial O2 content is 100 mL/L. At rest, the tissues need to remove
about 50 mL/L of oxygen from the blood passing through them. To achieve this
mixed venous content, Po2 will need to fall to about 5.3 kPa
(40 mmHg) (A in Fig. 8c) when [Hb] = 150 g/L and about 3.6 kPa (27 mmHg) (B)
when [Hb] 75 g/L. The reduced venous and hence capillary Po2
reduces the partial pressure gradient driving diffusion of oxygen to the
tissues, which is adequate at rest but which may become inadequate in exercise
when oxygen consumption increases.
Figure 8c also shows the
dissociation curve for blood that has 50% of oxygen-binding sites occupied by
carbon monoxide (CO, dashed line). Arterial oxygen content is 100 mL/L, but
there is also an altered shape and leftward shift of the dissociation curve,
because CO binding increases the affnity of the remaining (CO-free) sites for
oxygen. This impairs oxygen release in the tissues. Mixed venous Po2
will now have to fall to 2 kPa (15 mmHg) (point C) to release the 50 mL/L
required, and this will greatly reduce the pressure gradient for diffusion. At
about 50-60% carboxyhaemoglobin, symptoms of impaired cerebral oxygenation
(headache, convulsions, coma and death) are severe, whereas anaemic patients
with the same arterial oxygen content are typically asymptomatic at rest.
Haemoglobin has a high aff nity for CO ( 240 times that for oxygen), so
breathing even at low concentrations causes a progressive increase in the
cherry-red carboxyhaemoglobin. A cherry- red complexion is sometimes a feature
of CO poisoning, although pallor and cyanosis (discussed in Chapter 23)
are more common.
Other Respiratory Pigments
Fetal haemoglobin, HbF,
differs from adult haemoglobin, HbA, in that there are two γ -chains
instead of two β-chains. The HbF dissociation curve lies to the left of
that for HbA, reflectin its higher O2 affinit . This difference is
enhanced by the double Bohr shift: in the placenta Pco2
moves from the fetal to maternal blood, shifting the maternal curve further
right and the fetal curve further left. The high affinit of HbF relative to HbA
helps transfer oxygen from mother to fetus, and even though blood returning
from the placenta to the fetus in the umbilical vein has a Po2
of only about 4 kPa (30 mmHg), its saturation is 70%. Oxygen transport in the
fetus is also helped by a high [Hb] of about 170-180 g/L.
Myoglobin, the respiratory
pigment found in muscle, is composed of a single haem group attached to a
single globin chain. With no cooperative binding, its dissociation curve is
hyperbolic. It is also far to the left of HbA and its high affinity means that its oxygen store is only released
when local Po2 is severely reduced, for example in heavy exercise.
