Malaria and Sickle-Cell

  1. Explain why fibers do not form in either oxygen-rich or oxygen-poor environments in individuals who have HbA molecules.  

In an environment with saturation of oxygen, for example, the lungs, the HbA molecules are not attracted to each other and occur as free distributed molecules in the BRC. However, is an area with limited oxygen level, the deoxygenated HbA molecules have a hydrophobic pocket. They however lack a mutant valine to act as a donor. The process of the hemoglobin sticking together occurs due to the genetic mutation that causes a change in a single amino acid residue. This change causes the HbA molecules to associate with each other as opposed to situation in the cellular environment. 

  1. Explain why fibers do not form in oxygen-rich conditions in individuals who have HbS molecules.  

The HbS molecules contain a mutant molecule referred to as the valine. The appears like a hydrophobic protrusion on the surface of the hemoglobin. However, in an environment saturated with oxygen, the HbS molecule have no opportunity to interact with each other since the hydroponic pockets are absent.

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  1. Explain why fibers do form in oxygen-poor conditions in individuals who have HbS molecules. 

In an environment with low oxygen saturation, the HbS aggregate to form polymers. In such an environment, the HbS molecules have their hydroponic pockets protruding. When the valine protrusion of a single HbS molecule interacts with that of another HbS molecule they join to form long fibers.

  1. Explain how the formation of fibers results in the sickling of RBCs. 

The formation of the long fibers forces the red blood cell to stretch in size for them to accommodate this new shape. The fibers make the cell membrane to be more rigid and thereby adapting the sickle shape. 

  1. a. Explain why heterozygous individuals might have less severe malaria infections.

It has been noted that individuals who are heterozygous tend to have less severe malaria infection. The individual who are heterozygous have been noted to have an innate resistance to malaria. A common explanation to the reduce level of infection amongst the heterozygous individuals is that the shape of the sickle cells makes it more difficult for the malaria parasites to infect these cells. With the sickled cells, there is an increased rate of phagocytosis which causes the destruction of the deformed cells. In this process, the parasites are also destroyed thereby reducing the severity of the malaria infection. 

b. Explain why the same responses that provide some protection to a heterozygous individual would be very harmful in an individual who is homozygous for sickle cell haemoglobin. 

Among the homozygous patients with the sickle gene, there is a higher count of the RBCs that are sickle-shaped. Most of these cells are destroyed. If such individuals are infected with the malaria, the causal parasites are destroyed alongside the RBCs. While this may appear to be beneficial in reference to the immunity against of malaria, it causes a more serious problem due to the reduction of number of red blood cells. This causes these individuals to suffer from sickle cell anemia which is more severe and lethal among the homozygous individuals. The red blood cells infected with the malaria causing parasite also sticks to the wall of the capillaries which blocks the flow of the blood to the vital organs.

  1. Now that you have examined the mechanism by which fibers form and cause cells to sickle, explain how the formation of sickled cells leads to anaemia.

The sickle shaped red blood cells get marked by the immune system for destruction. This process of destruction leads to a situation where the rate of destruction of the red blood cells is faster than the rate of production which leads to anemia. It can also be observed that the sickle-shaped red bloods cells are not flexible and tends to stick to the blood vessels thereby causing clogging of the blood vessels. This causes a situation where some vital organs fail to get enough oxygen thereby leading to anemia.

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