Biochemical Basis of Sickle Cell Disease - Essay Example

Biochemical Basis of Sickle Cell Disease of the Biochemical Basis of Sickle Cell Disease Sickle cell Anemia is a condition caused by lack of enough hemoglobin or red blood cells in the blood stream. Red blood cells are manufactured in the bone marrow and are of two types namely, normal red blood cells that live for around three months in the blood stream before dying and abnormal red blood csells that have a life span of about 10 to 20 days, thus giving the bone marrow no time to produce more red blood cells. Sickle cell anemia is a genetic disease characterized by a mutation in hemoglobin, resulting in hemoglobin polymerization and resultant cell deformation, especially when there is a deficiency of or low oxygen conditions. Normally, the mutation is in the beta chain and gives rise to hemoglobin S (HbS); thus, the sickling process is accelerated as the concentration of Hbs increases. Generally, the signs and symptoms of sickle cell disease usually begin in early childhood, with some of the characteristic features including low number of red blood cells, repeated infections and periodic episodes of pain (Jones, 2008). In the body, normal blood cells are donut-shaped and move easily through the blood vessels. Red blood cells contain a rich protein called hemoglobin that is responsible for carrying oxygen from the lungs to the rest of the body. Sickle cells are abnormal hemoglobin that occurs as mutation, causing the cells to develop a crescent shape, thus blocking blood flow, and causing pain and damage of organs affected. Distortion of these cells increases the risk of infections in sickle cell anemia patients. A person who is heterozygous for the hemoglobin gene will have fewer sickle shaped red blood cells and mild case of sickle cell anemia while a homozygous person for sickle cell is likely to experience high number of sickle cells and a full-blown case of the disease (Kawthalkar, 2012). Mutation of the HBB gene causes sickle cell; the hemoglobin consists of four proteins two alpha-globin and two beta globins. The HBB gene provides instructions for the making of the beta-globin, which has different versions resulting from multiple mutations. One such gene mutation is the production of abnormal versions of beta-globin known as the HbS; other mutations in the sickle cell anemia include the HbC and HbE. The DNA sequence in sickle cell anemia carriers is the main reason why the disease is mutational. This means that those suffering from the gene mutation of sickle cell are propagated from the presence of these genes (Kawthalkar, 2012). The sickle cell anemia is an inherited and lifelong disease; patients inherit two genes for the sickle hemoglobin, one from each parent. However, there are instances when people inherit a sickle cell hemoglobin gene from one parent and a normal gene from the other parent, leading to a condition called the sickle cell trait. The mutation of the sickle cell trait can only lead to sickle cell anemia in their offspring but those who have the sickle cell trait are not likely to have the disease. When both parents have a normal gene and abnormal gene, their offspring has a 25 percent chance of inheriting the normal gene; however, others have a 50 percent chance of inheriting one normal gene and an abnormal gene while 25 percent have a chance of inheriting the abnormal gene. Sickle cell anemia can be diagnosed before birth; here, doctors use a sample of amniotic tissue as early as 10 weeks into pregnancy, with the tests aimed at looking for abnormal hemoglobin (Peterson, 2008). The HbS polymerization rate is concentration dependant and dilution of the hemoglobin by increased hydration will delay erythrocytes will delay the onset of the sickling process. The dense dehydrated erythrocytes are important contributors to the vaso-occlusive manifestations of sickle cell anemia and its inhibition of the hydration process may reduce to a reduced number of sickle crises. Polymerization of HbS molecules in the red blood cells is responsible for the sickling of red blood cells. Polymerization results in deoxygenating, which is a time dependent process. The HbS molecules aggregate to form a polymer of critical size - this is the rate limiting nucleation phase. The time between deoxygenating and formation of the polymer of critical size is called the delay stage, which is significant in the sickling and unsickling process due to the oxygenation and deoxygenating of red blood cells into the lungs (Plasmar, 2004). The signs and symptoms of the sickle cell anemia mainly start showing as early as four months in infants. Although the symptoms vary in intensity, some have mild symptoms while others experience severe symptoms that lead to hospitalization. Common symptoms associated with the disease include shortness of breath, headaches, paler than normal skin and coldness in hands and feet while symptoms related to pain may be felt on bones, lungs abdomen and joints. The pain is related to the blocking of blood flow to limbs and other body organs. Pain associated with anemia can be acute or chronic whereby, acute pain is more common than chronic pain, ranges from mild to severe, and can last from hours to days before it subsides. On the other hand, chronic pain is mainly felt in bones and can be mentally draining as it lasts longer than acute. Unfortunately, the pain is more disturbing in sickle cell anemia patients, and if left to continue for a long time, it can lead to damage of the bones, lungs, kidneys, eyes and even the heart. This painful crisis can be controlled in sickle cell patients by hydrating the patient, thus lowering the pain. Nevertheless, infections in this case are highly likely to increase as the immune system becomes low or deteriorates (McGuire & Beerman, 2012). The risks associated with sickle cell anemia are numerous and affect the whole body system. Hand and foot syndrome condition constitutes the swelling of feet and hands, and this may lead to pain, swelling and fever, which may tend to leave sickle cell patients immobile, especially if it affects the joints of the limbs and feet. Organs’ failure is also imminent with sickle cell anemia; for instance, the spleen, which filters out abnormal red blood cells while fighting infections, may develop a spleen crisis due to overflow of trapped red blood cells, and in severe cases, patients may require undergoing blood transfusions. Sickle cell anemia patients get infections easily and have a hard time fighting them. This may be due to the damage of the spleen, which is responsible for fighting infections. It is worth noting that infants and young children with damaged spleens are more likely to experience infections as their immune system is still not yet fully developed and is more prone to infections that travel through the blood stream. Multiple organ failure happens in two out of three of the major organs including lungs, liver and kidneys. Nevertheless, symptoms associated with these complications are fever, rapid heartbeat, breathing problems and sudden bouts of fatigue (Hoffman etal, 2013). Sickle cell anemia does not have a cure and any treatments can only help relieve symptoms and treat complications but not completely eradicate the disease. The goal in treating sickle cell anemia is to relieve pain and prevent organ failure and damages while at the same time controlling complications. Infants are treated with antibiotics to prevent infections and receive the needed vaccination while parents of sickle cell anemia infants are educated on how to manage it coupled with initial treatments. Nevertheless, early diagnosis is important in order to prevent any potential complication, especially in infants and offsprings of already infected adults. Mild pain can be treated with over-the- counter drugs, heating pads and plenty of rest and intake of fluids. It is also important to provide IV fluids to dehydrated patients in order to increase the production of hemoglobin in the body. Other medications such as hydroxyurea prompt the body to make fetal hemoglobin; this medication helps in the prevention of red blood cells from sickling, and those using this medication require less blood transfusion and experience reduced pains. Although this treatment is commonly used, it may reduce the number of white blood cells, which are the highly important in protecting the body from opportunistic infections, thus exposing the patient to rising chances of infections in the body. It is therefore important to enhance medical follow-ups to ensure the blood cells remain normal, and medicines can be adjusted in case of severe side effects. To prevent complications, patients undergo blood transfusions to prevent life threatening problems like stroke and organ failure. Nevertheless, the downside of too many transfusions may lead to an increase in iron, which must be reversed in order to return the blood composition to the right status and normalize blood PH (Peterson, 2008). Newer treatments have been adopted through research, and they include the blood and marrow stem cell transplant and gene therapy. The blood and marrow stem cell transplant can work well with patients of sickle cell; however, stem cells transplanted must be closely matching the donor who are normally close family members (this limits the number of donors available). The transplant process is considered risky and may lead to serious side effects, thus forcing doctors to advice and advocate this process to only younger patients with severe sickle cell anemia. Gene therapy is the introduction of a normal gene into the bone marrow. Here, researchers believe this method will lead to production of normal red blood cells. This therapy is like turning on or off the sickle cell hemoglobin. Researcher’s advice on the use of this type of therapy will help increase the number of blood cells in the body, thus decreasing levels of infections. New medication such as decitabine, which works more like hydroxyurea fetal hemoglobin, helps prevent blood cells from sickling, thus improving the management of anemia. Adenosine A2 is a receptor agonist that reduces pain-related complications while 5-HMF medication is a natural compound that binds red blood cells and increases their oxygen intake (Steinberg, Forget, & Higgs, 2009). Sickle cell anemia is a lifelong disease that does not have a cure. Therefore, many medical institutions and practitioners tend to manage it through the use of medications such as antibiotics for infections and analgesics for pain relief. Researchers are still looking into different methods that may help in inhibiting the sickling of red blood cells. The only treatment that has been deemed to provide a total cure is the bone marrow transplant that tends to improve the production of red blood cells. The production of red blood cells in the system increases oxygen in the body, thus reducing the amount of sickling cells in the body. In conclusion, the mutation of the sickle cell gene can affect everybody regardless of age, as it has been observed to manifest in both infants and adults. This has prompted researchers to conduct studies aimed at establishing treatment methods and solutions for this disease; however, recent observations have established increased cases of improvement in lifestyles as a way of curtailing the spread of the disease. Managing the disease is one of the many procedures that medics have used over the years to ensure they have the correct treatments. Sickle cell anemia patients require services of caregivers who understand the disease well in order to ensure it does not become critical, mainly due to the fact that the disease does not have a known cure. As noted earlier, the disease may become fatal if left to continue unattended for long, as it tends to damage bone marrow and joints to an extent of disabling patients; thus, early diagnosis and proper management of symptoms and related infections is very important. Nevertheless, recent studies have shed some glimpse of hope in cure of the disease through bone marrow transplant, especially due to the fact that this procedure enhances oxygen circulation in the body thus improving the process of producing red blood cells. Reference List Acton, Q A 2013, Sickle Cell Anemia: New Insights for the Healthcare Professional: 2013 Edition: ScholarlyBrief, Scholarly, Atalanta, Georgia editions. Hoffman, R, Benz, E, Silberstein, L, Leslop, H, Weitz, J & Anastasi, J 2013, Hematology: Diagnosis and Treatment, Elsevier Health Sciences, New York. Jones, P 2008, Sickle Cell Disease: Genes & Diseases, infobase publishing, New York. Kawthalkar, S 2012, Essentials of Haematology. JP Medical Ltd, New Delhi. McGuire, M & Beerman, K 2012, Nutritional Sciences: From Fundamentals to Food, Cengage Learning, Ohio. Peterson, J M 2008, Sickle Cell Anemia: Genetic developmental diseases and disorders, The Rosen Publishing Group, New York. Plasmar, R L 2004, Focus on Sickle Cell Research, Nova Publishers, New York. Steinberg, M, Forget, ‎B, & Higgs, D 2009. Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management, Cambridge University Press, Cambridge. Read More