Hereditary Spherocytosis: The Metabolism of Erythrocytes in the Peripheral Blood and in the Splenic Pulp

S ummary . Na + transport was studied in intact red cells and membrane preparations (‘ghosts’) of patients with hereditary spherocytosis (h. s.). Ouabain‐insensitive efflux was greater than normal in ghost preparations as well as in intact cells, findings which arc consistent with a membrane defect in h.s. red cells. Ouabain‐sensitive (‘pump’) sodium efflux was normal in h.s. membrane preparations, but was increased in intact cells and the latter probably reflects changes secondary to the increased Na + influx in these cells. In h.s., red cells are trapped and destroyed in the spleen and we studied splenic pulp red cells in a group of h.s. patients at splenectomy. These cells showed greater osmotic fragility, higher Na + and lower K + concentrations than did peripheral red cells. Membrane permeability to Na + was not greater than in peripheral red cells but the ouabain‐sensitive (‘pump’) Na + efflux was reduced. Despite this, ATP concentration and ATPase activity were found to be normal. Low levels of 2,3‐diphosphoglyceric acid were noted in splenic red cells but ATP turnover was normal. Since failure of the Na + pump occurs in h.s. splenic red cells despite adequate substrate (ATP) and an intact ATPase system, it is suggested that the abnormality results from a change in the red cell membrane 4 which reduces the function of the pump. These characteristics of splenic red cells are similar to those found in normal red cells following in vitro incubation at 37°C. This supports the concept that cell death in h.s. results from a deterioration in membrane function secondary to substrate deprivation in the stagnant circulation of the splenic pulp.