<aside> 🩸 Sickle cell disease is the name for a group of inherited health conditions that affect the red blood cells. The most serious type is called sickle cell anaemia.
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Sickle-Cell Anemia → Issues in Comprehensive Pediatric Nursing
“The globin portion of the hemoglobin molecule consists of two alpha and two beta chains. Each of these polypeptide chains contains hundreds of amino acids arranged in a sequential manner. Sickle-cell anemia represents a structural alteration of the globin proteins. The amino acid valine is substituted for glutamate in the sixth position on the beta chains. This abnormal hemoglobin is referred to as Hb S. A child with sickle-cell anemia is homozygous for this disorder and is said to have Hb SS disease.”
“Normally, the erythrocyte is disk-shaped with a smooth surface. This form allows the red blood cell to traverse the microcirculation without producing obstruction. The Hb SS erythrocyte, however, assumes a crescent shape under the condition of deoxygenation. Sickling occurs when oxygen saturation falls... Therefore some amount of erythrocyte sickling occurs in the venous circulation. Conversely, the erythrocyte resumes its normal shape upon reoxygenation in the lungs… This abnormal red cell is rigid and has a rough surface area that can easily obstruct the microcirculation. The resultant stasis produces oxygen deprivation, acidosis, and further sickling.”
“Sickled cells are more susceptible to entrapment and destruction in the reticuloendothelial system of the spleen, which causes chronic hemolytic anemia. Whereas the normal erythrocyte has a life-span of 120 days, sickled red blood cells have a limited existence of 15 to 20 days… The bone marrow partially compensates for this destruction by increasing red blood cell production to a level four to five times greater than the norm.”
Insight into the complex pathophysiology of sickle cell anaemia and possible treatment → European Journal of Haematology
“Sickle cell anaemia is highly prevalent in Africa and India. Fewer cases occur in the Mediterranean region and in the Middle East. In North European countries, this condition was historically unknown, but with migration, SCA has become more prevalent.”
“Epidemiological studies have shown that this condition has been naturally selected in tropical areas where malaria is endemic as the sickling impairs reproduction of [strains of malaria].”
“Haldane formulated the hypothesis that, in terms of Darwinian selection, genetically, people may have a different risk of dying when exposed to a parasitic organism and, although the gene is harmful, its frequency would increase in case it offers protection against the infectious disease when a population is exposed to the parasite… Haldane was the first to suggest that thalassemia heterozygotes are likely to be more resistant to malaria.”
“This mechanism is called balanced polymorphism… the disadvantage of SS homozygotes is balanced by the advantage of AS heterozygotes. Homozygous SCA patients are more likely to die of vaso‐occlusive events or to have a short life expectancy because of ongoing vascular occlusion and associated organ damage. Conversely, healthy subjects with normal haemoglobin pattern (HbAA) are more susceptible to malaria infections, particularly during early childhood with high risk of severe malaria infection (e.g cerebral malaria), which carries severe mortality risk. HbS hinders malarial parasites multiplication, and therefore, heterozygotes (HbAS) have an advantage against this disease. The level of HbS in heterozygotes is generally too low to promote severe vaso‐occlusive events. These individuals are both protected against malaria and SCA and survive up to the age of reproduction. This creates an evolutionary advantage for this allele, accounting for the high penetrance of the mutation in malarial areas. ”
“The sickling process within red cells occurs as direct consequence of the substitution of a single nucleotide (A to T) in the codon for amino acid 6. The change converts a glutamic acid codon (GAG) to a valine codon (GTG).”
“…valine is a hydrophobic amino acid. During deoxygenation, valine hydrophobicity attracts hydrophobic regions of adjacent β‐chains facilitating the polymerisation of haemoglobin molecules. Formation of Hb aggregates is a thermodynamically unstable event, and under particular conditions, the number of molecules aggregating significantly increases and reaches a critical mass, known as the critical nucleus, after which point addition of further molecules to this compound generates a stable complex. As this progresses, he reaction becomes autocatalytic and heterogeneous nucleation occurs on the surface of pre‐existing polymers, leading to robust polymer generation, causing erythrocytes sickling”