Cause / Pathogenesis Of Sickle Cell Anemia Research (Essay Sample)

SICKLE CELL ANEMIA
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Under normal circumstances, the erythrocytes in the blood are biconcave in shape, and can quickly move through the blood vessels to supply oxygen and nutrients to the various organs of the body. Sickle cell anemia is a devastating hematological disorder with distinguished erythrocytes that are unusual in shape due to the existence of modified hemoglobin (Hb) molecule. The red blood cells (RBCs) in sickle cell anemia are irregular, in the shape of a sickle, which makes them be fragile and rupture easily.
The sickled RBCs can prevent the normal movement of blood to organs by blocking the blood vessels, resulting in the inadequate supply of blood, which can lead to organ damage. Most of the sickled RBCs are eliminated from the body, leading to a reduction in the number of healthy RBCs and low oxygen levels in the body. Sickle cell anemia is a hereditary disease that is caused by a mutation in the genes that code for hemoglobin. This paper analyzes the pathogenesis, pathophysiology of sickle cell anemia and the sign and symptom of the disease.
Cause/pathogenesis of sickle cell anemia
The hemoglobin is a protein molecule that is made up of four iron molecules, two alpha molecules, and two beta globin molecules. The HBB gene is housed in the short arm of the eleventh chromosome, and codes for the production of beta-globulin molecules, while HBA gene codes for the production of alpha-globin and is located on the short arm of the sixteenth chromosome. A point mutation can occur in the HBB gene which can lead to the synthesis of the abnormal Hb. This modification can result in the amino acid valine being substituted by glutamic acid in the beta-globin molecule of the hemoglobin, resulting in an abnormal hemoglobin molecule that is in the shape of a sickle (HbS). Since the HBB gene is inherited from the parents, sickle cell anemia would occur when an individual inherits two copies of the HBS, one from each parent. Therefore, the genotype of a patient suffering from sickle cell anemia would be HBSS. A patient with a single ordinary hemoglobin gene and a single abnormal hemoglobin gene is known as a sickle cell carrier. When both parents are carriers, the chance of having a child with sickle cell disease is 0.25% as shown in the figure below.
The inheritance of Hemoglobin genes that can cause sickle cell anemia


Pathophysiology of Sickle Cell Anemia
Intracellular changes
A possible gene mutation in the hemoglobin molecule results in a sequence of abnormal intracellular reactions which interference with the cell membrane of the RBCs, resulting in blockage of the blood vessels and destruction of the RBCs. Typically, the hemoglobin molecules occur as single independent units in the RBCs whether it is carrying oxygen or not. The sickled hemoglobin also exists as separate units in the RBCs when they are carrying oxygen. However, when the abnormal hemoglobin releases the oxygen to the tissues and becomes deoxygenated, the sickle hemoglobin molecules becomes twisted in shape and binds together to form long chains or polymers, a process called polymerization. These polymers are rigid and insoluble and destroy the normal shape of the RBCs, causing them to bend and form a banana/sickle shape.
When the polymerization process continues for a long time, larger polymers are formed which can block the blood vessels, thus interfering with the normal flow of blood in the body. Also, the distortion of the RBCs interferes with their cell membranes and flexibility, which can make the RBCs to stick to the endothelium of the blood vessels, worsening the blockage of the blood vessels. The damage to the RBCs membrane can also result in an influx of calcium ions which causes dehydration of the RBCs.
When the RBCs pick up oxygen from the lungs, the abnormal hemoglobin (HbS), revert to their normal shape and solitary existence. By blocking the blood vessel, the volume of oxygen and nutrient reaching the tissue and organs is reduced, resulting in ischemia that can damage the organs. This process continues throughout the entire lifetime of the RBCs. The continued polarization and depolarization of the HbS in the RBCs results in repeated cycles of vascular occlusion and restoration of normal blood flow that causes reperfusion injuries to tissues and organs such as the lungs, the heart and the brain due to inflammation and the action of vascular oxidases. It can also lead to bone infarction and necrosis.
Pathophysiology of sickle cell anemia


Extracellular Changes
The sickled RBCs are prone to hemolysis which results in the release of the cytoplasmic contents such as the hemoglobin into the extracellular compartment. The extracellular hemoglobin molecules produce reactive hydroxyl and superoxide radicals which increase the consumption of nitric oxide in the body, resulting in the vasoconstriction of the blood vessels, systemic and pulmonary hypertension and stroke. The accumulation of the extracellular hemoglobin in plasma can strain the glomerulus filtration in the kidneys, leading to renal dysfunction. Excess hemoglobin in plasma can also prevent the degradation of the von Willebrand factor (VWF) proteins which are critical in homeostatic roles. The result is increased activities of the VWF, which activates platelets, resulting in the formation of tiny blood clots within the blood vessels which contribute to vascular occlusion.
Signs and Symptoms of Anemia
The most common symptom of sickle cell anemia is the anemia and fatigue. The RBCs in patients with sickle cell anemia is fragile and can easily be hemolyzed before the 120 days that an average RBC lives, leaving the patient with little quantities of healthy cells. This can result in fatigue since the cells have inadequate oxygen to energize them. Also, patients with sickle cell anemia experience cyclic pain that occurs when the sickle cells cause vascular occlusion of tiny blood vessels in the body. The pain can occur in the chest, abdomen, and joints and can vary in magnitude and duration.
Another symptom of sickle cell anemia is the swelling of hands and feet. The patients can experience painful swelling in the hands and feet due to the obstruction of blood flow to these regions. The obstruction of blood to the small blood vessels supplying the eyes and brain can damage the retina and the cerebral tissues resulting in impaired vision and stroke.
Patient with sickle cell anemia can also experience recurring infections. The increase rate of sickle cells destruction and the continuous production of new RBCs can damage the bone marrow that also produces white cells. The patient would become vulnerable to opportunistic infections such as pneumonia infections. Also, the patient can suffer from delayed growth. RBCs provide the body with oxygen and nutrients that are essential for growth and development. In sickle cell anemia, the reduction in the volume of RBCs can result in slowed growth and delayed puberty in children and adolescents.
Conclusion
Sickle cell anemia is a hereditary disorder of the blood that occurs from a gene mutation on the chromosome 11 that codes for the synthesis of beta globin of the hemoglobin molecule. The resulting abnormal hemoglobin produced, polarizes quickly in the absence of oxygen to form sickle-shaped red blood cells that cause vascular occlusion and ischemia that causes vision impairment, acute chest syndrome, stroke, and fatigue.
Bibliography
CDC. Sickle Cell Anemia: Complications and Treatment. Center for Disease Control and Prevention. /ncbddd/sicklecell/treatments.html 2017. Accessed October 30, 2017.
Desai, Chirag, and Biren Shah. "A Review of Pathophysiology of Sickle cell Anemia and it...