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Penetration and destruction of the erythrocyte membrane. A, The membrane is penetrated and destroyed by the intracellular formation of polymers, resulting in spicule formation. B, Interruption of the binding between the membrane and protein skeleton results in a massive exchange of lipids between the inside and outside of the cell. This process is called flip-flop. An abnormal membrane skeleton causes an increased flip-flop. The result in the spicule is a change of the chemical structure, increasing the tendency toward coagulation of sickle cell blood (prethrombotic state). C, The relationship between the protein skeleton of the erythrocyte and lipid membrane is shown. (Adapted from Franck [11]; with permission.)

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