RBC disorders (4) Flashcards
Haematolytic anaemia:
Anaemia due to increased red blood cell destruction (or increased erythropoiesis) – broken down
Microskeletal defects (membrane defects):
Hereditary spherocytosis – defect in the cytoskeleton (gene defect for the protein that makes up the membrane)
Membrane permeability defects (membrane defects):
Hereditary stomatocytosis – ion channel defects
Deficiencies in Hexose Monophosphate Shunt (Enzymopathies):
Glucose 6-Phosphate Dehydrogenase (6PD) Deficiency – defects the way the blood cell gets energy via glycolysis
Deficiencies in the Emben-Myerhof Pathway (Enzymopathies):
Pyruvate Kinases deficiency
Membrane disorders:
- Hereditary spherocytosis (HS) – this lecture and most common
- Hereditary Elliptocytosis (HE) – this lecture
- Hereditary Stomatocytosis
- Hereditary Xerocytosis
- Autoimmune haemolytic anaemia
- Paroxysmal nocturnal haemoglobinuria
Hereditary spherocytosis (HS):
- Most common hereditary HA in Northern Europeans
- Usually autosomal dominant, variable expression – 1 parent
- Defects in proteins involved in vertical interactions between membrane cytoskeleton and lipid bilayer
- Red cells normal biconcave shape but become increasingly spherical as progress through spleen/RE system – not flexible
- RBC Die prematurely - Every time it goes through the spleen, it gets more narrow and therefore more spherical, showing defects
What happens in HS?
Majority of genetic defects that occur in hereditary spherocytosis are Ankyrin and spectrin and band 3 in the plasma membrane
You either end up with reduced synthesis of the protein, an unstable protein or dysfunction
The problems of HS:
- need to be able to say which protein influences what
- band 3 will have genes that have reduced function which is incooperated onto the membrane
- the membrane is destabilised which loses its flexible links to the lipid bilayer – increased production of red blood cells when there is loss
- you have a loss of surface area to volume ratio
- often the cells are small and lose biconcave shape, becomes trapped in splenic chords and splenic conditioning occurs when RBC try to squeeze through the spleen
- leading to further loss (more spherical cell) and then is broken down, has a limited number of time it can move through but is eventually destroyed as it cannot handle the pressure
Clinical features of HS:
- Anaemia
- Jaundice typically fluctuating – bile products used to break down red blood cells, leading to the person becoming yellow as the break down doesn’t occur efficiently
- Splenomegaly – usually the answer to write in exams
Haematological findings (in the lab, blood count, on a blood film):
- Reticulocytes 5-20% - pre red blood cell (normal retic value is 1-1.5% in anaemia)
- Blood film: microcytes
Investigation & Treatment:
- Osmotic fragility test increased
- Splenectomy principle form of treatment (can remove which increases the lifespan) – need spleen to protect against routine infections
Laboratory test: Osmotic fragility
- Results representative of both typical and severe spherocytosis are shown.
- A “tail,” representing very fragile erythrocytes that have been conditioned by the spleen, is common in many HS patients prior to splenectomy.
Not done very often, but place red blood cells in a hypotonic solution, more solutes in the solution than inside the cell so water moves into the cell, membrane is looked at
Hereditary Elliptocytosis (HE):
- Various membrane protein abnormalities including spectrin, protein 4.1 and glycophorin C
- EL2 and EL3: Most common genetic defects are in genes for α-spectrin or β-spectrin
Red cell metabolism:
- Red cell maturation - Loss of organelles
- However mature red blood cells still need energy to maintain a healthy cell
