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 RBC S that are sickle shaped inflexible and easily destroyed.

All right. So RBC S are produced through erythropoiesis which occurs within the bone marrow.

The bone marrow releases immature rbcs called reticulocytes into the circulation or 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 alpha globin and two beta 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 through 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 beta 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.

Ok. So the mutation to the HBB gene involves changes to the sequence of amino acids in the beta globin chain or the sixth amino acid glutamic acid is replaced with valine as a result.

Two normal alphaglobin and two mutated betaglobin chains give rise to defective hemoglobin known as hemoglobin S also called HB S.

Now, hemoglobin S can usually function normally. However, there are certain circumstances where it begins to malfunction.

This includes hypoxemia, acidosis, dehydration, low temperatures and even stress in these situations. Hemoglobin S undergoes polymerization where the hemoglobin S molecules aggregate and form long rigid fibers.

These fibers distort the shape of the rbcs in a process known as sickling or the cells take on a crescent shape. At the same time, calcium begins to shift into the cell.

While potassium and water shift out of the cell further dehydrating the cells and contributing to the sickling process. These sickled cells are also more fragile and easily destroyed, leading to fewer functional rbcs to transport oxygen which intensifies hypoxemia and to make matters worse.

Sickled cells are stiff and inflexible. So they easily lodge in narrow blood vessels which obstructs blood flow.

No clinical manifestations of sickle cell anemia vary in severity since RBCs affected by sickle cell disease only survive 10 to 20 days.

The reduced number of functional rbcs can result in symptoms of tissue hypoxia and anemia including fatigue, weakness, power and dyspnea.

Additionally, hepatomegaly or liver enlargement occurs as extramedullary hematopoiesis or production of rbcs outside of the bone marrow attempts to compensate for the reduced number of rbcs in the spleen.

Autosplenectomy may occur or the continued trapping of sickled cells obstructs blood flow leading to splenic infarct while an accelerated destruction of malfunctioning rbcs by the spleen can cause hyperbilirubinemia and jaundice.

Now, individuals can also have intermittent episodes of extensive sickling called crises. These crises can be categorized as vasoocclusive aplastic sequestration and hyperhemolytic.

First. A vasoocclusive crisis occurs when the sickled rbcs clump together and block vascular blood flow resulting in inflammation, vasoconstriction, tissue ischemia and necrosis which causes intense pain and organ damage.

Common sites for this to occur include the bones, lungs, brain and penis. For example, hand foot syndrome can occur when the bones are affected, leading to painful swelling in the hands and feet.

And acute chest syndrome can present as cough and chest pain vasoocclusion in the brain can manifest as stroke and in the penis, priapism or a prolonged painful erection can occur and lead to permanent tissue damage.

Next, aplastic crises occur when the bone marrow temporarily ceases erythropoiesis. Despite the need for new RBCs, aplastic crises are typically preceded by a viral infection that shuts down the bone marrow leading to profound anemia and hypoxia manifesting as fatigue weakness, dizziness and tachycardia.

Then there's sequestration crises which occur when large numbers of sickled RBC S pool in the spleen. This can lead to a reduced circulating blood volume, manifesting as hypovolemia shock and even death.

Lastly, hyperhemolytic crises occur when there is excessive destruction of rbcs precipitated by certain infections or medications.

It manifests with fever, jaundice and worsening anemia. All right, as a quick recap, sickle cell anemia is one of the most common types of sickle cell disease, which is a genetic condition resulting in red blood cells or rbcs that are sickle shaped inflexible and easily destroyed.

The reduced number of functional rbcs can lead to manifestations of tissue hypoxia and anemia, including fatigue weakness, pa, and dyspnea