RBC Membrane Defects
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Spherocytosis, spectrin ankyrin spherocyte
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RBC Membrane Defects
- 2. Meet The Red Cell Shaped like a flattened, bilaterally indented sphere, a biconcave disc In fixed, stained blood smears, erythrocyte appears circular, with a diameter of about 7 to 8 μm and an area of central pallor. Average values for the mean cellular volume in normal subjects range from 80 to 100 fl. Highly elastic and deformable. The normal mature erythrocyte as visualized by the scanning electron microscope (×9,800). (Courtesy of Dr. Wallace N. Jensen.) The erythrocyte can pass through a vessel of about 3 μm in maximum diameter
- 3. Meet The Red Cell ► Durability of Red cell is remarkable ► No nucleus to direct regenerative processes ► No mitochondria available for efficient oxidative metabolism ► No ribosomes for regeneration of lost or damaged protein ► No de novo synthesis of lipid Images of red blood cells (top) and a human hair (bottom) taken with a confocal microscope Still survives for 120 days!!!
- 4. Red Cell Membrane Structure Erythrocyte membrane that is normal in structure and function is essential to survival of red cell Accounts for the cell's antigenic characteristics Maintains stability and normal discoid shape of cell Preserve cell deformability Retain selective permeability
- 5. Red Cell Membrane Structure ►The red cell membrane consists of: Proteins 52% Lipids 40% Carbohydrates: 8%
- 10. Hereditary Spherocytosis Haemolytic disorder characterized by numerous microspherocytic erythrocytes seen in the blood film. Most common inherited anaemia in Northern European descent
- 11. Micro spherocytes Small. Dark. Very round. Hyperchromic cell With no central pallor.
- 12. Hereditary Spherocytosis 75% autosomal dominant fashion 25% Rarely autosomal recessive Loss of membrane surface area relative to intracellular volume spherical shape decreased deformability splenic destruction
- 13. Hereditary Spherocytosis ADAR Defect in 5 possible membrane proteins
- 14. Pathophysiology The anemia is genetically passed down from one generation to another. The basic defect in HS is a membrane abnormality caused by dysfunctional and/or deficiencies in one or more of the followings: Spectrin, Ankyrin, Band 3, and Protein 4.2, all of which are vital components (structural proteins) of the cell membrane.
- 17. Specifically, these lead to: Reduced cell surface area Impaired flexibility, and Increased permeability to sodium, which the cells pump out to stabilize the osmotic fragility. - Such process requires a lot of ATP consumption.
- 18. Pathophysiology Despite all of that, the cells life span remains unaffected until the cells reach the spleen, where glucose and ATP levels are insufficient. Therefore, the cells cannot pump out the extra sodium leading to an increased intracellular sodium concentrations and subsequently, increased water content.
- 19. Pathophysiology This leads to the swelling and rigidity of the cells which cannot negotiate the spleen’s microcirculation where they get trapped and phagocytozed.
- 20. Pathophysiology of HS A) Reduced density of membrane skeleton destabilizes overlying lipid bilayer B) Loss of Band 3 lipid-stabilizing effect
- 22. Laboratory diagnosis CBC Hb: low PCV: low RBCs count: low MCV: low MCH: normal MCHC: increase in half to two-third of patients. Note: HS is the only disease in which MCHC is elevated.
- 23. PBP As the name indicates, the characteristic feature of this anemia is the presence of microcytic spherocytes in peripheral blood. • Anisocytosis is prominent: • mixture of microspherocytes and large polychromatic cells. • Poikilocytosis other than spherocytes is not common. Reticulocyte count: increase (5-20%)
- 24. Micro spherocytes Small. Dark. Very round. Hyperchromic cell With no central pallor.
- 26. Special tests Osmotic fragility test: increased Autohaemolysis test: increased Direct coomb’s test: negative.
- 28. Biochemical findings: Indirect bilirubin: increase LDH: increased Urobilinogen: increased Haptoglobin level: decrease Analysis of red cell membrane protein: determine the exact abnormality of red cell membrane
- 29. Differential diagnosisDifferential diagnosis Other acquired causes of spherocytes in peripheral blood film: 1.Warm Autoimmune hemolytic anaemias. 2.Hemolytic transfusion reactions.
- 30. Treatment Splenectomy (surgical removal of the spleen) is the treatment of choice for symptomatic hereditary spherocytosis and can be done when a child is five years of age or older. Treatment before the age of five consists of daily folic acid supplementation.
- 31. Hereditary spherocytosis. A typical Wright-stained peripheral blood smear from a patient with autosomal dominant hereditary spherocytosis is shown. Small, dense, round, conditioned spherocytes that lack central pallor are visible throughout
- 32. Hereditary Elliptocytosis The HE syndromes are a family of genetically determined erythrocyte disorders characterized by elliptical red cells on the peripheral blood smear. Inheritance of HE is autosomal dominant (except HPP) the HE variants occur with an estimated frequency of 1:1,000 to 5,000. HE has a worldwide distribution, but is more common in malaria endemic regions with prevalence approaching 2% in West Africa.
- 33. The mechanistic basis for decreased membrane mechanical stability in HE is weakened “horizontal” linkages in membrane skeleton due either to defective spectrin dimer-dimer interaction or a defective spectrin-actin-protein 4.1R junctional complex. The mechanism by which these protein defects result in elliptocyte formation is not clear.
- 34. A B C A: Common Hereditary elliptocytosis B: Hereditary pyropoikilocytosis. Red cell budding and fragmentation. C: Southeast Asian ovalocytosis