Pyruvate kinase (PK) deficiency causes chronic haemolytic anaemia. The SPECIFIC biochemical mechanism of red cell destruction in PK deficiency involves:

• A Accumulation of 2,3-BPG that shifts the oxygen dissociation curve and reduces oxygen delivery
• B Accumulation of fructose-1,6-bisphosphate toxic to the RBC membrane
• C Deficient ATP generation causing failure of Na+/K+-ATPase, membrane rigidity, and premature splenic destruction of rigid RBCs ✓
• D Lack of NADPH production causing oxidative haemolysis

Explanation

Red blood cells depend entirely on glycolysis for ATP (lacking mitochondria). PK deficiency blocks the last ATP-generating step of glycolysis (phosphoenolpyruvate → pyruvate). ATP depletion impairs the Na+/K+-ATPase pump, causing cellular swelling and loss of biconcave shape. These rigid, osmotically fragile spherocytes are trapped and destroyed in the spleen (extravascular haemolysis). Paradoxically, 2,3-BPG accumulates proximal to the block — this actually improves oxygen delivery but does not prevent haemolysis. NADPH deficiency is the mechanism in G6PD deficiency.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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Written and medically reviewed by the StethoPrep medical team.