Hereditary spherocytosis asif new
Transcript of Hereditary spherocytosis asif new
Hereditary spherocytosis
By
Muhammad asif Zeb
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
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
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
Red cell membrane
The red cell membrane consists of:
Proteins 50%
Lipids 40%
Carbohydrates: 10%
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
Structure of RBC membran
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
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
EPIDEMOLOGY
o Most common inherited membran disorder
o 75% autosomal dominant fashion
o 25% Rarely autosomal recessive
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 ,
ADDUCIN PROTEIN
DEFECTIVE
HORIZONTAL
PROTEIN
INTERACTIONS
RESULT IN
MEMBRANE
INSTABILITY OR
PERMEABILITY
ELLIPTOCYTOSIS
SKELETAL PROTEIN ABNORMALITIES
Spherocytes formation
Pathophysiology of HS
spherocytosis
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
Moderate HS
60 to 75 percent of cases.
Moderate anemia
Have high reticulocyte counts,
Elevated serum bilirubin concentrations.
splenomegaly mild to moderate
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.
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
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%
Routine chemistry testing
Bilirubin: Increased
Indirect bilirubin
Urine urobilinogen: increased
Methaemalbumin: Increased
LDH: Increased
Haptoglobin: Decreased
Haemopexin: Decreased
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.
Red cell membrane detection
Red cell membrane can be detected by SDS
-PAGE
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