Sickle Cell Anemia

ISU Essay: Sickle Cell Anemia

Background/introduction

Blood is essential to human survival. This fluid is the transportation system of the body; it delivers all necessary nutrients that cells need in order to function properly. The largest component of blood is comprised of red blood cells. These cells are the body’s principle means of transporting oxygen from the lungs to all body tissues. They are perfectly suited for this function because red blood cells contain hemoglobin, an iron-based protein molecule that binds to oxygen. This bond results in oxygen being circulated as blood travels (Medical and Health Encyclopedia, 1995, p.411).

Normally, in an average man, there are 5 million red blood cells per cubic millimetre. If this number decreases to 4 million or less, it results in a condition known as anemia. Any abnormalities in size, shape, or hemoglobin content can also account for an anemic state. Many types of this disorder exist, including sickle cell anemia, a disease that is closely related to hemoglobin (Medical and Health Encyclopedia, 1995, p.35).

What is it?

Sickle cell anemia is a disorder that directly affects the circulatory system, or red blood cells in particular. Normally, the body manufactures red blood cells that are disc-shaped. All are smooth and flexible, enabling them to pass easily through the smallest blood vessels. However, the red blood cells of individuals affected by sickle cell anemia are distorted. They take on a sickle shape, also becoming sticky, rigid, and fragile.

Sickled Cell Normal RBC

(credit:http://carnegieinstitution.org/first_light_case/horn/lessons/images/red%20blood%20cells.JPG, 2008)

All of these characteristics lead to difficulty traveling in blood vessels, resulting in blockages and a very low oxygen supply for the body (Young People’s Encyclopedia, 1993, p.1545).

The Cause

Unlike other cells, red blood cells lack a nucleus and organelles. About 97% of the red blood cell’s dry content is composed of the macromolecule, hemoglobin. This molecule is key for explaining the sickle cell phenomenon.

The DNA required to make hemoglobin involves six genes. Four of these genes code for one half of the molecule, called the alpha chain while the remaining two code for the other half, the beta chain. Each chain is divided into two subunits (or globins) with its own non-protein heme group that is able to bond with one oxygen molecule. Therefore, each hemoglobin molecule can bind to four oxygen molecules in total. These are the characteristics of the normal hemoglobin A. However, if one of the six genes is altered, forms of hemoglobin other than hemoglobin A will result (http://sickle.bwh.harvard.edu/scd_background.html, 2008).

The beta-globin gene that is found on the short arm of chromosome eleven is the determinant of sickle cell anemia. A slight alteration in just one nitrogenous base in the DNA sequence coding of this gene is simply all that is necessary to cause a lifetime of medical complications. This change causes a point mutation in the beta-globin chain. In other words, glutamic acid, an amino acid that normally fills the sixth position in the beta chain, is replaced by another amino acid called valine (Biology 11, 2002, p. 202). When two mutated beta-globins unionize with the two wild-type (normal) alpha globins, hemoglobin S is created (http://sickle.bwh.harvard.edu/scd_background.html, 2008). This variant has different properties than hemoglobin A. Under both oxygenated and deoxygenated conditions, hemoglobin A molecules remain separate from each other, allowing the red blood cells to maintain the same shape. However, even though hemoglobin S allows the red blood cells to retain their normal shape in an oxygenated environment, they become drastically different once they are oxygen-deprived. Subsequently, the abnormal amino acid valine causes a weak attraction force between the hemoglobin S molecules, causing them to polymerize. They form a twisted bundle made up of fourteen strands (http://sickle.bwh.harvard.edu/scd_background.html, 2008).

(credit: http://sickle.bwh.harvard.edu/scd_background.html, 2008)

Problems arise because these polymers cause the cell membrane to distort out of their round shape, becoming rigid and sickle-shaped instead (http://en.wikipedia.org/wiki/ Sickle-cell_disease, 2008). Once the erythrocytes pick up oxygen again, the hazardous attraction force disappears, returning the membrane to its original shape. This cycle of assembling and dissembling quickly deteriorates both the cell membrane and the hemoglobin itself. Although erythrocyte production is increased significantly, it still cannot keep up with the destruction rate of those sickle cells. A normal red blood cell has an average lifespan of about 120 days, while a sickle cell can only live for about 20 days. This reduces blood count drastically (http://www.kidshealth.org/parent/medical/ heart/sickle_cell_anemia.html, 2008).

Inheriting the disease

Sickle cell anemia is an autosomal recessive genetic disease, inherited from the parents. This means that the child must receive two sickle cell genes, one from each parent, in order to be fully affected. In other cases where one sickle cell gene is inherited along with a normal gene, the child has a condition known as sickle cell trait.

Sickle cell trait is different from sickle cell anemia. People who have sickle cell anemia are affected by the abnormal hemoglobin SS, while people with sickle cell trait do not. Most people who have sickle cell trait do not even know it because they never experience the side effects. These people simply have the gene that can cause sickle cell anemia. Therefore, they run the risk of passing the disease down to their own children. Parents who both have sickle cell trait may produce a child who has a 25% chance of having sickle cell anemia and 50% chance of having the sickle cell trait. The risk increases if either parent has sickle cell anemia.

Although anyone can inherit this disease, it is known that the victims most affected have ancestors from the African heritage. Others include those from the Mediterranean, Middle East and India (http://en.wikipedia.org/wiki/Sickle-cell_disease, 2008).

History and Evolution

Scientists and researchers believe that sickle cell anemia evolved many years ago from a spontaneous single mutation

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