Pyruvate Kinase Deficiency - Pathophysiology

Pathophysiology

Erythrocytes manufacture ATP through glycolysis. A deficiency in pyruvate kinase, the enzyme that potentiates the last step of glycolysis (phosphoenolpyruvate converted to pyruvate), results in red blood cells (RBCs) with decreased energy.

The events leading to hemolysis are still not well understood, but it seems that the lack of ATP impairs the Na+/K+-ATPase and other ATP-dependent processes, leading to a cellular loss of K+ and water and an intracellular accumulation of Na+. This cellular swelling is comparable to ischemic changes in which cells denied of O2 suffer from an ATP deficiency. This swelling causes rigidity of the RBC and eventually splenic hemolysis from an inability to distort through splenic sinusoids. Partial splenectomies are sometimes performed as a treatment for anemias due to an underlying inability for RBC deformation (hereditary spherocytosis and pyruvate kinase deficiency). This is usually reserved for severe transfusion-dependent anemias as removal of the spleen confers a susceptibility to encapsulated organisms.

The buildup of reaction intermediates can also increase the level of 2,3-bisphosphoglycerate (2,3 BPG) in the cells and affect tissue oxygenation. This will cause a "right shift" in the hemoglobin oxygen saturation curve, implying a decreased oxygen affinity for the hemoglobin and earlier oxygen unloading than under normal conditions. As a result, individuals with pyruvate kinase deficiency may have a greater capacity for physical activity than others with similarly low hemoglobin levels.