Zach Cooper
Case 2
In a normal, healthy patient, red blood cells are flexible and can easily navigate through blood vessels in
order to safely reach their target destination. In many cases, these cells must be capable of changing
shape in order to squeeze through capillaries. By doing so, oxygen can be delivered to the target tissues
with a low risk of the RBC rupturing.
Unfortunately, this process becomes unsuccessful in the case of sickle cell anemia. In these instances,
fibers that are long and insoluble are formed by the depolymerization of deoxyHbs. Due to these twisted
helical fibers, this “sickle” shape increases the risk of cells becoming stuck in small blood vessels. These
sickle-shaped cells then become vulnerable to lysis and can contribute to many unfavorable health
consequences, including pain and anemia.
One factor that can influence the development of abnormal RBC shape is oxygen availability. According
to Rodwell et al, “a low PO2, such as that at high altitudes, exacerbates the tendency to polymerize” 1.
Therefore, the most likely answer is answer choice E, as oxygen would decrease the polymerization of
these long and insoluble fibers and therefore mitigate the sickling by these cells.
The other answer choices would likely fail to reduce the frequency of sickling. Iron could theoretically
increase the quantity of RBC production in some contexts, but would not necessarily change the shape
of the RBC structures. Similarly, there is little reason to suspect that glucose or histidine would have an
influence on the PO2 or the shape of the RBC structure. Additionally, compared to normal cells, sickle
cells already demonstrate increased 2-3 BPG and decreased affinity for oxygen 2, so it is highly doubtful
that 2-3 BPG would help and theoretically could actually contribute to additional health complications.
Case 4
Carbon monoxide poisoning is a serious health condition that can lead to devastating consequences.
Carbon monoxide has an affinity for hemoglobin that is 210 times greater 3-4 than the affinity of oxygen.
When the majority of the hemoglobin in the blood becomes bounded to carbon monoxide, oxygen
becomes displaced and cannot reach its target tissues, leading to a decrease in oxygen consumption.
During aerobic respiration, oxygen plays an essential role as the final electron acceptor in the electron
transport chain. In this woman’s case, if electrons are unable to be passed down this electrochemical
gradient, ATP production will decrease. Additionally, carbon monoxide has been demonstrated to inhibit
Complex IV and cytochrome c oxidase activity 5, further contributing to an impediment in the ETC.
During ATP production in an individual with a healthy ETC, NADH becomes oxidized to NAD+. In the case
of this woman, however, NADH in the mitochondria cannot undergo oxidation because oxygen is not
being consumed and ATP is not being produced. As a result, mitochondrial NADH will continue to
increase. Furthermore, as this woman continues to resort to anaerobic metabolism in order to continue
providing ATP, this will further stimulate an increase in NADH in the cytosol.
Therefore, the most appropriate answer is indicated by choice B, involving a decrease in ATP production
and oxygen consumption followed by a consequential increase in mitochondrial and cystolic NADH.
References
1 Rodwell VW, Bender DA, Botham KM, et al. Harper's Illustrated Biochemistry. McGraw-Hill Education.
2018; page 151.
2 Charache, S., Grisolia, S., Fiedler, A. J., & Hellegers, A. E. (1970). Effect of 2, 3-diphosphoglycerate on
oxygen affinity of blood in sickle cell anemia. The Journal of clinical investigation, 49(4), 806-812.
3 Blumenthal, I. (2001). Carbon monoxide poisoning. Journal of the royal society of medicine, 94(6), 270-
272.
4 Hlastala, M. P., McKenna, H. P., Franada, R. L., & Detter, J. C. (1976). Influence of carbon monoxide
on hemoglobin-oxygen binding. Journal of applied Physiology, 41(6), 893-899.
5 Alonso, J. R., Cardellach, F., López, S., Casademont, J., & Miró, Ò. (2003). Carbon monoxide
specifically inhibits cytochrome c oxidase of human mitochondrial respiratory chain. Pharmacology &
toxicology, 93(3), 142-146.
