Hemolysis in Hereditary Spherocytosis. Panel A shows the structure of a normal red cell and a spherocyte; insets show interactions between the membrane and cytoskeleton mediated by the proteins band 3, Rh, band 4.2, and ankyrin; glycophorin C, band 3, Rh, band 4.1, and actin; and α-spectrin and β-spectrin. Gene mutations of any of the shaded proteins can lead to deficiencies that cause hereditary spherocytosis. Disruption of the connection between the lipid bilayer and cytoskeleton results in microvesiculation, membrane loss, and spherocyte formation. Panel B shows the red pulp of the spleen in which red cells transit from the cords to the sinusoids through tight spaces between endothelial cells. Spherocytes are less deformable owing to a reduced surface-to-volume ratio and are selectively retained in the cords, where further destruction or hemolysis occurs. #Pathophysiology #Honc #IM #Spherocytosis #Hemolysis #HereditarySpherocytosis #NEJM