Hereditary spherocytosis
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Hereditary spherocytosis (HS) is a genetically determined hemolytic anemia characterized by spherical red blood cells, primarily caused by an ankyrin deficiency. The condition presents in varying severities, with symptoms ranging from mild to severe anemia and splenomegaly, and is diagnosed using an osmotic fragility test. Additionally, HS has a predominately autosomal dominant inheritance pattern and can lead to complications such as gallstones and increased bilirubin levels.
Hereditary spherocytosis
- 1. Hereditary spherocytosis By Muhammad asif Zeb Lecturer Hematology Khyber Medical University Peshawar
- 2. objective What is spherocytosis What is normal red cell membrane and its function What is pathophysiology of HS Complication of HS Diagnosis of HS Differential diagnosis of HS
- 3. Hereditary spherocytosis A genetically determined haemolytic aneamia characterized by spherical shaped RBC,s Characteristic appearance, round cells with smaller diameter Lack of area of central pallor, decrease surface to valume ratio
- 4. NORMAL RED CELL DESTRUCTION RBC completes 120 days Of life span Changes in cell membrane occurs Enzyme activity declines Effete cells less deformable than normal Recognized by macrophages Phagocytosis and cell death
- 5. Red cell membrane The red cell membrane consists of: Proteins 50% Lipids 40% Carbohydrates: 10%
- 6. Functions of red cell membrane Erythrocyte membrane that is normal in structure and function is essential to survival of red cell Maintains stability and normal discoid shape of cell Preserve cell deformability Retain selective permeability
- 7. Structure of RBC membran
- 8. INTERACTIONS OF RBC MEMBRANE PROTEIN AND LIPIDS VERTICAL INTERACTIONS Perpendicular to cell membrane . Includes interactions between skeletal lattice on cytoplasmic side to integral proteins and lipids of membrane It stabilizes lipid bilayer defects lead to uncoupling of lipid bilayer from underlying skeleton thus selective loss lipid layer microvesicle formed Proteins include: Ankirin, Band 3 ,Glycoporin and Protein 4.2 etc
- 9. HORIZONTAL INTERACTIONS Parallel to plane of cell membrane includes spectrin head to head attachments and protein interaction at junction complexes Disruption in these interactions lead to destabilization of membrane poikilocyte e.g. Spectrin Actin
- 10. EPIDEMOLOGY o Most common inherited membran disorder o 75% autosomal dominant fashion o 25% Rarely autosomal recessive
- 11. DISORDER MEMBRANE DEFECT ABNORMAL MEMBRANE FUNCTION ERYTHROCYTE MORPHOLOGY HEREDITARY SPHEROCYTOSIS PRIMARY 50% ankirin DEFECIENCY SECONDARY band 3, then spectrin and other DEFECIENCY DEFECTIVE VERTICAL PROTEIN INTERACTION WITH LIPID LOSS OF LIPID BILAYER SPHEROCYTE FORMED SPHEROCYTOSIS HEREDITARY ELLIPTOCYTOSIS DEFECTIVE SPECTRIN HEAD TO HEAD INTERACTION DEFECT IN BAND 4.1, ACTIN , DEFECTIVE HORIZONTAL PROTEIN INTERACTIONS RESULT IN MEMBRANE ELLIPTOCYTOSIS SKELETAL PROTEIN ABNORMALITIES
- 14. spherocytosis
- 15. Form of HS on the bases of Severity Mild HS 20 to 30 percent have of cases. These p No anemia, Little splenomegaly or jaundice,. Normal hemoglobin levels
- 16. Moderate HS 60 to 75 percent of cases. Moderate anemia Have high reticulocyte counts, Elevated serum bilirubin concentrations. splenomegaly mild to moderate
- 17. Severe HS 5 percent marked hemolysis and marked anemia, hyperbilirubinemia, 17-70 micro mole/L Marked splenomegaly Gall bladder stones The pattern of inheritance is almost always recessive and the parents of an affected patient are usually asymptomatic.
- 18. Diagnosis BLOOD PICTURE Hb = 7-14g /dl May fall below 7 in crises May be normal in compensated hemolysis MCV =N or slightly reduced MCH= Normal Mchc= Increased Plt = normal or decreased
- 19. Peripheral smear ANISOCYTOSIS Spherocyte POIKILOCYTOSIS Polychromatic cells Target cells Nucleated RBC can be present severe cases Plt decreased if splenomegaly Retic Usually 5-20% Sometimes 50-70%
- 21. Routine chemistry testing Bilirubin: Increased Indirect bilirubin Urine urobilinogen: increased Methaemalbumin: Increased LDH: Increased Haptoglobin: Decreased Haemopexin: Decreased
- 22. Osmotic fragility test Principle When an erythrocyte is placed in a hypotonic sodium chloride-(NaCl) solution, a net influx of solvent (water) into the cell-will occur and the cell will swell. If the cell size reaches a certain point, the cell membrane will become leaky and hemoglobin will diffuse out (hemolysis). If the NaCl solutions hypotonic enough, the cell will rupture. The degree of hemolysis can be measured by determining the absorbance of the supernatant using a spectrophotometer.
- 25. Red cell membrane detection Red cell membrane can be detected by SDS -PAGE
- 26. Summary Genitic disorder of red cell membran Mainly due to ankirin deficiency Extravascular hemolysis Severity depend on mutation in gene Diagnosis on osmotic fragility test and PAGE. SDS