Hereditary spherocytosis

By

Muhammad asif Zeb

Lecturer Hematology

Khyber Medical University

Peshawar

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