Increased Cell Membrane Permeability in the Pathogenesis of Hereditary Spherocytosis *

Abstract

Hereditary spherocytosis (HS) red cells, if packed or deprived of glucose, lost viability rapidly when subsequently transfused into normal subjects, yet inordinately consumed glucose through acceleration of the Embden-Meyerhof pathway. HS cells accumulated more Na than normal during incubation and manifested abnormally great influx and efflux of Na24. Ouabain, by in-hibiting active cation transport, diminished glycolysis toward normal and caused rapid accumulation of Na in HS cells without affecting normal red cells. Diminishing sodium influx by suspension of HS cells in sucrose, reduced osmotic swelling, prolonged in vivo survival, and prevented the abnormal autohemolysis characteristic of incubated HS cells. The primary defect of HS red cells appears to be in the cell membrane which is abnormally permeable to sodium. Enhanced active sodium extrusion from the cells through activation of an ATPase system, provides extra energy for cation transport and stimulates glycolysis as well. These compensatory mechanisms suffice in the general circulation but fail during metabolic stress as with entrapment in the spleen.