Hereditary spherocytosis

Hereditary spherocytosis is an inherited condition related to RBC destruction. its diagnosis is require to differentiate immune hemolytic anemia and G-6-P-D deficiency anemia

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
oMost common inherited membran disorder
o75% autosomal dominant fashion
o25% 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 ,
ADDUCIN PROTEIN
DEFECTIVE
HORIZONTAL
PROTEIN
INTERACTIONS
RESULT IN
MEMBRANE
INSTABILITY OR
PERMEABILITY
ELLIPTOCYTOSIS
SKELETAL PROTEIN ABNORMALITIES

12. Spherocytes formation

13. Pathophysiology of HS

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
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