What is the pathophysiology of sickle cell anaemia?
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Sickle cell anaemia (SCA) is a hereditary disease caused by an abnormal haemoglobin S (HbS) in red blood cells. When deoxygenated, the HbS polymerizes, leading to intracellular gelation and subsequent haemoglobin polymerisation. This process can cause disruption of the red cell membrane, resulting in haemolysis and vaso-occlusive events. Additionally, leucocyte adhesion molecules and nitric oxide depletion contribute to endothelial damage. Recent studies have also shown that cell-derived microparticle generation is involved in vaso-occlusion. Endothelial damage is further perpetuated by impaired production or increased consumption of protective modulators such as protein C, protein S, and nitric oxide. Hydroxyurea is currently the only FDA-approved therapy for SCA, as it reduces haemoglobin polymerisation by increasing the production of foetal haemoglobin and L-glutamine. However, several new drugs have been tested in clinical trials to address these aspects of SCA pathogenesis .
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| The pathophysiology of sickle cell anaemia involves abnormal haemoglobin production due to an inherited point mutation in the β-globin gene, leading to haemoglobin polymerisation, red cell membrane disruption, haemolysis, and vaso-occlusive events. | |
| The paper provides a discussion on the pathophysiology of sickle cell disease, including the role of hemolytic and vaso-occlusive episodes, chronic inflammation, and hemostatic alterations. | |
1 Citations | The pathophysiology of sickle cell anemia involves vaso-occlusive crises, endothelial damage, organ failure, and systemic consequences caused by the stiffening of deoxygenated erythrocytes. |
| The pathophysiology of sickle cell anemia involves vaso-occlusive crises, endothelial damage, organ failure, and systemic consequences caused by the stiffening of deoxygenated erythrocytes. | |
| The provided paper discusses the pathophysiology of haemolysis in patients with sickle cell disease, but it does not specifically address the pathophysiology of sickle cell anaemia. |
Related Questions
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OAn overview of the nature of the disorder including epidemiology in sickle cell anemia ?5 answersSickle cell anemia (SCA) is a severe monogenic disorder with a high prevalence worldwide. It is recognized as a global health concern by the World Health Organization (WHO). SCA affects approximately 5% of the world population, with varying estimates in different continents. The disease has reached high population frequencies in sub-Saharan Africa, the Mediterranean, the Middle East, and India. In these regions, SCA is associated with a high mortality rate, especially in low- and middle-income countries. The disease is also prevalent in scheduled populations in India, which are socioeconomically disadvantaged communities. The clinical features of SCA include crisis, pulmonary pathobiology, muscular, neurological, hepatobiliary, and ophthalmological complications, as well as frequent sepsis and priapism. Early diagnosis of SCA is crucial, and point-of-care techniques offer hope for detection and management of the disease. Overall, there is a need for further research to better prevent the adverse consequences of SCA and reduce its long-term health burden.
How molecular structure is important through Hemoglobin and Sickle Cell Disease?4 answersThe molecular structure of hemoglobin is crucial in understanding sickle cell disease (SCD). SCD is caused by a single amino acid substitution in the beta chain of hemoglobin, resulting in the formation of HbS aggregates under reduced oxygen tension. The polymerization of deoxygenated HbS leads to the characteristic sickling of red blood cells (RBCs). This process is driven by O2 tension and intracellular HbS concentration. The sickling of RBCs is associated with a complex network of cellular changes, contributing to the inflammatory vasculopathy and potential organ damage in SCD. Understanding the molecular pathogenesis of SCD has paved the way for the development of therapeutic strategies targeting HbS polymerization. Additionally, the role of erythrocyte dehydration in cell sickling has been identified, as increased cellular HbS concentration enhances the polymerization tendency of HbS. Overall, the molecular structure of hemoglobin plays a crucial role in the pathophysiology and treatment of SCD.
Why molecular structure importantly affect Hemoglobin and Sickle Cell Disease?3 answersThe molecular structure of hemoglobin plays a crucial role in the development of sickle cell disease (SCD). SCD is caused by a genetic mutation that results in the substitution of glutamic acid with valine in the hemoglobin molecule. This mutation leads to the polymerization of deoxygenated sickle hemoglobin (HbS) into long strands, causing the characteristic sickle-shaped red blood cells. The polymerization of HbS is influenced by various non-covalent interactions between amino acid residues, such as hydrophobic and electrostatic interactions. The formation of HbS fibers and their subsequent growth contribute to the pathogenesis of SCD. Additionally, the concentration of HbS within the red blood cells and the dehydration of these cells also affect the polymerization tendency of HbS. Understanding the molecular mechanisms underlying HbS polymerization is crucial for developing effective therapeutic strategies for SCD.
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