Biomedical Engineering Reference
In-Depth Information
of the partial pressure must be such that the 2 mM are given up when the partial pressure
changes from 95 to 40 mmHg. Furthermore, during strenuous exercise, the oxygen demand
doubles and 4 mM must be liberated for a partial pressure change from 95 to 27 mmHg.
The evolutionary solution is to put an oxygen-binding protein into circulating blood to
increase the oxygen content of blood. To stay within the vascular bed, such a protein would
have to be 50 to 100 kD in size. With a single binding site, the required protein concentra-
tion for 10 mM oxygen is 500 to 1,000 g/l, which is too concentrated from an osmolarity
standpoint, and the viscosity of such a solution may be 10-fold that of circulating blood,
which is clearly impractical. Further, circulating proteases would lead to a short plasma
half-life of such a protein.
Having four sites per oxygen-carrying molecule would reduce the protein concentration
to 2.3 mM, and confining it to a red cell would solve both the viscosity and proteolysis pro-
blems. These indeed are the chief characteristics of hemoglobin. A more elaborate kinetic
study of the binding characteristics of hemoglobin shows that positive cooperativity will
give the desired oxygen transfer capabilities both at rest and under strenuous exercise
(Figure 6.23).
Perfusion rates in human bone marrow cultures:
The question of how often the growth
medium that supports cells should be replenished is important in designing cell culture
conditions. Normally, the in vivo situation provides a good starting point for experimental
optimization. A dynamic similarity analysis can give insight into this question.
Δ
~2 mM
Δ
~4 mM
exercise
normal
27
40
100mm Hg
FIGURE 6.23
A schematic of hemoglobin-oxygen binding curves and oxygen delivery. The change in oxygen
concentration during passage through tissues (i.e., oxygen delivery) is shown as a function of the concentration of
oxygen in blood.
Modified from [3].
