• Normally, RBCs remain soluble and flexible in the blood when passing through the circulation at varying degrees of oxygen saturationSickle-Cell-Anemia-Occlusion-1Mechanism
  • In Sickle cell anemia: substitution of VALINE for GLUTAMIC ACID in position 6 of the Beta-chain => This substitution results in an alteration of the quaternary structure of the hemoglobin molecule
  • When de-oxygenated, the mutated RBCs will form long polymers & cross linking; thus becoming rigid and insoluble
  • MECHANISM: The loss of the hydrophilic AA for a hydrophobic AA will allow it to interact with hydrophobic AA helices on another B chain and form aggregates
  • These sickled cells form polymers with themselves; they lose flexibility and a collection of rigid sickle cells will cause occlusion in the micro circulation
  • Upon returning to oxygenated tissue, the cells will be able to return to their discoid cell shapes
  • Repeated sickling will cause ion channel dysfunction (loss of Ca2+/K+), cellular dehydration (will be permanently sickled and destroyed in the spleen)

REFERENCES

  1. Deepa Manwani and Paul S. Frenette. Vaso-occlusion in sickle cell disease: pathophysiology and novel targeted therapies. ASH Education Book December 6, 2013 vol. 2013 no. 1 362-369
  2. Chapter 49: Disorders of Hemoglobin Structure: Sickle Cell Anemia and Related Abnormalities. Kavita Natrajan; Abdullah Kutlar. Williams Hematology, 9e
  3. Odièvre M-H, Verger E, Silva-Pinto AC, Elion J. Pathophysiological insights in sickle cell disease. The Indian Journal of Medical Research. 2011;134(4):532-537.

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