Respiration Module

Blood gas carriage
blood carries oxygen to tissues
carbon dioxide away from tissues

Oxygen transport
oxygen is not very soluble in water
at pO2 of 13.3 kPa it dissolves 0.13 mmol.l-1
at rest we need 12 mmol oxygen per minute
which is contained in 92l

Oxygen transport
even if all the oxygen could be extracted
cardiac output would have to be impossibly high
need a chemical reaction to transport more per litre of blood

Oxygen binding
many substances will react chemically with oxygen
so getting it into the blood is not a problem
getting it out again is the trouble
need a very reversible reaction

Respiratory pigments
a number of pigments bind oxygen reversibly
oxygen combines reversibly with Haem
oxygenation not oxidation

Dissociation curves
the reversibility of oxygen binding is represented by a dissociation curve
plot of amount O2 bound vs pO2
total content then bound + dissolved
Partial Pressure (kPa)
Oxygen Bound (mmol)
Saturation
Dissolved O2
Bound O2
Myoglobin

Dissociation curves
chemical binding saturates above a given pO2
the amount of oxygen bound then depends on how much pigment
so dissociation curves normally expressed as percentage of amount of oxygen bound at saturation
and are independent of pigment concentration

Using dissociation curves
tells you how much oxygen will be bound or given up
when blood is moved from one pO2 to another
Partial Pressure (kPa)
Saturation (%)
Saturation
Dissolved O2
Myoglobin
100%
B
A
A
B
Given Up

Using dissociation curves
work out the difference in fractional saturations
between the two pO2‘s
and multiply it by the amount bound at full saturation
to tell you how much oxygen is taken or given up

Haemoglobin
a tetramer - 2 alpha & 2 beta subunits
each subunit has one haem + globin
overall molecule has variable quaternary structure

The moods of Haemoglobin
the molecule may be tense
or relaxed

The moods of Haemoglobin
relaxed haemoglobin
is laid back and
loves to bind oxygen

The moods of Haemoglobin
tense haemoglobin
is uptight
and does not bind oxygen well

The moods of Haemoglobin
haemoglobin gets anxious
when pO2 is low
so it is hard to bind the first oxygen
as most molecules are in the tense form

The moods of Haemoglobin
as oxygen binds haemoglobin
feels better and relaxes
so binding the next oxygen is much easier
as many more molecules relax

Haemoglobin dissociation curve
initially the relationship between pO2 and binding is shallow
but binding facilitates further binding
so the curve steepens rapidly as pO2 rises
until saturation
a sigmoid curve
pO2
3.5
10
Saturation (%)
50
100

Haemoglobin dissociation curve
haemoglobin saturated above 8.5 kPa
virtually unsaturated below 1 kPa
half saturated at 3.5-4 kPa
so saturation changes greatly over narrow range of pO2
highly reversible reaction

Haemoglobin in the lungs
alveolar pO2 13.3 kPa
so Hb well saturated
Hb in normal blood 2.2 mmol.l-1
each molecule binds 4 oxygen
so oxygen content 8.8 mmol.l-1

Haemoglobin in the tissues
tissue pO2 varies, but typically 5 Kpa
haemoglobin now about 65% saturated
change in binding = 100 - 65%
oxygen given up 8.8 x 0.35 mmol.l-1
c 3 mmol.l-1
pO2
Saturation (%)
50
100
Lungs
Tissues
Given up

Haemoglobin in venous blood
still has over half its oxygen bound
so tissues could remove more
how?

Tissue pO2
if lower more oxygen will be given up
how low can it get?

Tissue pO2
must be high enough to drive oxygen out to cells
cannot fall below 3 kPa in most tissues
the higher the capillary density the lower it can fall (cf heart muscle)

Getting more oxygen off Hb
the mood of haemoglobin also depends on pH
the molecule is more relaxed in alkaline conditions
and more tense in acid
pO2
Saturation (%)
50
100
Lungs
Tissues
Given up
Bohr Shift
Alkaline
Acid

The Bohr shift
in acid conditions the dissociation curve shifts along the pO2 axis
so that at any pO2 Hb binds less oxygen

In the tissues
pH is lower
so extra oxygen given up
higher temperature has similar effect
pO2
Saturation (%)
50
100
Lungs
Tissues
Given up
Bohr Shift
Alkaline
Acid

Maximum unloading
in tissues where pO2 can fall low
conditions are acid and warm
about 70% of bound oxygen is given up