Factors affecting sickling in sickle cell anemia are?
Ans. is 'a' i.e., HbS concentration; 'b' i.e., HbA; 'c' i.e., pH Factors affecting sickling Amount of HbS and interaction with other hemoglobins. o Most impoant factor for sickling is the amount of HbS and its interaction with other types of hemoglobin. o In homozygous individuals, all the hemoglobin in red blood cell is HbS, and undergo sickling. o In heterozygous, only 40% of hemoglobin is HbS --> Sickling does not occur because HbA (remaining 60% of normal hemoglobin) has an inhibitory effect on polymerization of HbS. o Fetal hemoglobin HbF also has inhibitory effect on sickling of HbS ----> Newborns do not manifest the disease until they are 5 to 6 months of age, when the amount of HbF in the cells falls close to the adult level. o HbC has a greater tendency to copolymerize with deoxygenated HbS. 2. Hemoglobin concentration o The rate of HbS polymerization is strongly dependent upon the hemologbin concentration per cell i.e., MCHC. o Higher HbS concentration increase the probability that aggregation and polymerization will occur during any given period of time. o Thus, intracellular dehydration, which increases the MCHC, faciliatates sickling. o Conversly, conditions that decrease MCHC reduce disease severity e.g., when sickle cell anemia occurs with athalassemia 3. Deoxygenation with HbS o Polymerization of HbS occurs only in deoxygenated state. o A decrease in pH reduces the oxygen affinity of hemoglobin, thereby increasing the fraction of deoxygenated HbS at any given oxygen tension and augmenting the tendency of sickling. 4. The length of time red cell are exposed to low oxygen tension. o Normal transient times for red cells passing through capillaries are not sufficient for significant aggregation of deoxygenated HbS to occurs. o Hence, sickling of red cells is confined to microvascular beds where blood flow is sluggish. o This is normally the case in spleen and bone marrow which are predominantly affected by sickle cell disease.
HbS concentration
HbA
pH
All