✔️ Inherited as Autosomal Dominant (Ⓜ️NEMO> Sickle Cell Disease is a SAD disease; S=SCD, AD=Autosomal Dominant)
✔️ A single DNA base change ( Beta chain) causes SCD
✔️ DNA base change is Adenine for Thymine & the resultant amino acid change is Valine for Glutamic Acid ( Ⓜ️NEMO> Addition of bases other than Thymine results in Valueless Goods )
✔️ Thus Hb S is produced. As Valine is hydrophobic, the deoxygenated Hb is less water soluble and gets precipitated & polymerized inside the RBC
✔️ This polymerization slightly reduces the overall affinity for O2; otherwise the affinity for O2 is same for Hb A and Hb S
✔️ These changes also make the RBS more rigid and contributes to sickling and microvascular occlusion
✔️ Regarding hypoxaemia, HbS will precipitate at a PO2 of 5–6 kPa (37-45 mm of Hg). As venous PO2 lies in this range, in case of homozygous individuals having only abnormal Hb will have continuous sickling
✔️ Patients with sickle cell trait experience sickling at much lower partial pressures (2.5–4 kPa / 19-30 mm of Hg )
✔️ Sickledex test produces a turbidity and becomes positive even with a very small amount of Hb S: so it CAN NOT differentiate between homo & heterozygous states
Reference: Smith T, Pinnock C, Lin T. Fundamentals of Anaesthesia, 3rd edn. Cambridge: Cambridge University Press, 2009; pp. 234–5
#Anesthesia , #hematology , #medicine , #SickleCellDisease
