<prompt> What is the cause of sickling of RBC in sickle cell disease?Decreased SolubilityDecreased StabilityAltered FunctionAltered 02 binding capacity  <response>: In sickle cell disease glutamic acid is replaced by valine. The charge and location of this substitution cause HbS to be conveed from a soluble state into a polymer when it undergoes structural changes that accompany release of oxygen. Hypoxia, acidosis, and hypeonicity facilitate polymer formation. The polymerization of hemoglobin cause the red cell to transform from a deformable, biconcave disk into a rigid, sickle shaped cell. Ref: Rudolphs Fundamentals of Pediatrics By Abraham M. Rudolph, Pages 528-30 