THE RELATIONSHIP BETWEEN KINETICS AND PATHOPHYSIOLOGY

The transformation of sickle hemoglobin molecules into arrays of fibers is the primary event in the pathophysiology of sickle cell disease. The process involves two types of nucleation: homogeneous nucleation in bulk solution, and heterogeneous nucleation onto other polymers. The polymers grow from each homogeneous nucleus in domains which ultimately become radial. Monomer diffusion into a domain can create density gradients between domains. Both types of nucleation are exquisitely concentration sensitive and can occur in times as short as milliseconds, while alignment and diffusion are less sensitive and take seconds or more. These various processes and their kinetics are reviewed in light of their role in the pathophysiology.