Hereditary Spherocytosis, Splenomegally and the RBC cytoskeleton

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1 and 2: SSFSE MRI abdomen. Severe splenomegally(white arrows) and gallstones (red arrow). 3: Spleen after splenectomy in patient with hereditary spherocytosis. 4: Diagram of the RBC sub membrane cytoskeleton

HEREDITARY SPHEROCYTOSIS is a genetic disorder occurring in about 1 of every 5000 caucasian births. Peripheral blood smears show many microspherocytes. Removal of spherocystes by the spleen is the cause of the anemia. Heterozygosity is lethal in utero. Hereditary spherocytosis may appear early or late in life. The RBC cytoskeleton and cell membrane are abnormal in hereditary spherocytosis.The RBC sub membrane cytoskeleton consists primarily of; spectrin (the main cytoskeletal component), actin, protein 4.1, protein 4.9, and ankyrin. Spectrin dimers are bound to protein 4.1. which in turn links spectrin to actin. The spectrin /actin /protein 4.1 complex is bound to the cell membrane by ankyrin and protein 3. With defective protein 4.1, spectrin dimers bind poorly to actin and the cell membrane. The lipid bilayer over the defective cytoskeleton is abnormal, forming the spherocyte. The defective membrane allows intracellular Na+ accumulation and the influx of intracellular fluid This results in increased RBC fragility and hemolysis. When a spherocyte transverses the spleen it is removed from circulation. Sequestration of RBCs results in severe splenomegally. Clinical features of hereditary spherocytosis include; anemia varying from mild to severe, splenomegaly (seen in >50% of ), jaundice, bilirubin-type gallstones and gout.

Sources: Whitney Williams http://www.clt.astate.edu/wwilliam/unit_02.htm