Sickle Cell Anemia

Sickle cell anemia, one of the most common types of sickle cell disease, is a genetic condition resulting in red blood cells, or RBCs, that are sickle-shaped, inflexible, and easily destroyed.

Alright, so, RBCs are produced through erythropoiesis, which occurs within the bone marrow.

The bone marrow releases immature RBCs called reticulocytes into the circulation where they mature into erythrocytes. Erythrocytes contain hemoglobin, which allows them to deliver oxygen to the body’s tissues.

Now, hemoglobin molecules are made up of four polypeptide chains of amino acids, which consist of two α-globin and two β-globin chains. Each of these polypeptide chains contains a heme group, which includes one iron atom where oxygen can bind. One oxygen molecule can bind to each polypeptide chain, allowing one hemoglobin molecule to carry up to four oxygen molecules.

RBCs have some unique characteristics that make them well-suited for oxygen transport. Their unique biconcave shape increases surface area for oxygen diffusion, and their flexible membrane allows them to change their shape so they can squeeze through tiny capillaries and then return to their original shape while staying intact. This gives them a degree of durability as they travel throughout the body’s network of blood vessels. In fact, RBCs have a lifespan of up to 120 days.

As RBCs age, become fragmented, or unhealthy, they’re ingested and destroyed by macrophages in the spleen and liver and replaced through erythropoiesis.

Sickle cell anemia is caused by a mutation in the HBB gene that provides the instructions for making β-globin. It’s inherited in an autosomal recessive pattern, meaning that an individual must inherit two mutated copies of the HBB gene, one from each parent, to get the disease.

On the other hand, if an individual has one mutated HBB gene and one normal HBB gene, then they have sickle trait, which doesn't typically result in anemia.

Risk factors include having a family history of sickle cell anemia and having ancestry from sub-Saharan Africa, as well as those with Mediterranean, Middle Eastern, and Indian descent.

Okay, so the mutation to the HBB gene involves changes to the sequence of amino acids in the β-globin chain, where the sixth amino acid, glutamic acid, is replaced with valine. As a result...two normal α-globin and two mutated β-globin chains give rise to defective hemoglobin, known as hemoglobin S, also called HbS. Now, HbS can usually function normally; however, there are certain circumstances when it begins to malfunction...