Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content +++ THE RED CELL MEMBRANE ++ The erythrocyte membrane accounts for 1 percent of total weight of the red cell. It plays an integral role in the maintenance of erythrocyte integrity. The lipid bilayer of the membrane and its associated skeletal proteins provide the flexibility, durability, and tensile strength for the erythrocyte to undergo large deformations during repeated passages through narrow microcirculatory channels. +++ HEREDITARY SPHEROCYTOSIS ++ Hereditary spherocytosis (HS) is the most common inherited anemia of persons of northern European descent. It is characterized by hemolysis of variable intensity, spherocytosis, and increased osmotic fragility of red blood cells. There is a favorable response to splenectomy. +++ Etiology ++ Accelerated red cell destruction results from deficiency or abnormality of one or more of the red cell membrane proteins, resulting in release of membrane lipids, decreased surface area, and formation of poorly deformable spherocytes. The underlying molecular defects are heterogeneous and defects affecting the same protein may produce different phenotypes, such as spherocytosis and elliptocytosis or ovalocytosis. Table 14–1 summarizes the relationship between red cell membrane proteins and disease phenotype. ++Table Graphic Jump LocationTABLE 14–1RED CELL MEMBRANE PROTEIN DEFECTS IN INHERITED DISORDERS OF RED CELL SHAPEView Table||Download (.pdf) TABLE 14–1 RED CELL MEMBRANE PROTEIN DEFECTS IN INHERITED DISORDERS OF RED CELL SHAPE Protein Disorder Comment Ankyrin HS Most common cause of typical dominant HS Band 3 HS, SAO, NIHF, HAc "Pincered" HS spherocytes seen on blood film presplenectomy; SAO results from 9 amino acid deletion β-Spectrin HS, HE, HPP, NIHF "Acanthocytic" spherocytes seen on blood film presplenectomy; location of mutation in β-spectrin determines clinical phenotype α-Spectrin HS, HE, HPP, NIHF Location of mutation in α-spectrin determines clinical phenotype; α-spectrin mutations most common cause of typical HE Protein 4.2 HS Primarily found in Japanese patients Protein 4.1 HE Found in certain European and Arab populations GPC HE Concomitant protein 4.1 deficiency is basis of HE in GPC defects GPC, glycophorin C; HAc, hereditary acanthocytosis; HE, hereditary elliptocytosis; HPP, hereditary pyropoikilocytosis; HS, hereditary spherocytosis; NIHF, nonimmune hydrops fetalis; SAO, Southeast Asian ovalocytosis.Source: Williams Hematology, 8th ed, Chap. 45, Table 45–2, p. 626. +++ Pathophysiology ++ With spectrin deficiency, larger areas of lipid bilayer are unsupported by the submembranous skeleton, causing loss of lipid in submicroscopic vesicles. The red cell membrane is more permeable to sodium, which activates the Na+, K+-ATPase pump and leads to K+ loss and dehydration. A decrease in the surface area-to-volume ratio and an increase in internal viscosity make spherocytes less deformable and unable to penetrate the slits between splenic cords and sinuses. While retained in the spleen, the red cells undergo a "conditioning effect," which renders the cells more spherical (loss of membrane surface area) and more osmotically fragile (lower surface area to volume ratio). Ultimately, the cells are engulfed by ... Your Access profile is currently affiliated with [InstitutionA] and is in the process of switching affiliations to [InstitutionB]. Please select how you would like to proceed. Keep the current affiliation with [InstitutionA] and continue with the Access profile sign in process Switch affiliation to [InstitutionB] and continue with the Access profile sign in process Get Free Access Through Your Institution Learn how to see if your library subscribes to McGraw Hill Medical products. Subscribe: Institutional or Individual Sign In Error: Incorrect UserName or Password Username Error: Please enter User Name Password Error: Please enter Password Sign in Forgot Password? Forgot Username? Sign in via OpenAthens Sign in via Shibboleth You already have access! Please proceed to your institution's subscription. Create a free profile for additional features.