Lecture 4: Disorders of Red Blood Cell Survival Flashcards
How long do red blood cells survive on average in circulation?
~120 days
What happens as red blood cells age?
Levels of ATP drop, and levels of Na+ and Ca2+ increase. The change in equilibrium, alongside increase in membrane fragility promotes destruction of cells by spleen.
What classifications of haemolytic disorders are there?
Site of haemolysis:
- Extravascular
- Intravascular
Intrinsic or extrinsic to the red cell
Nature or defect
Inherited or acquired
Acute or chronic
What is a haemolytic disorder?
Any disorder in which the lifespan of red blood cells is reduced.
How long will red blood cells survive in sickle cell anaemia?
~20 days, compared to the usual 120 days.
What are intrinsic haemolytic disorders?
Haemolytic disorders caused by genetics. This can be further sub-classified:
- Disorders of globin synthesis/structure
- Primary membrane disorders
- Enzyme disorders
What is the composition of a RBC membrane?
50% protein
10% carbohydrates
40% lipids (30% cholesterol, 10% free fatty acids, and 60% phospholipids)
What problems does a red blood cell have with lipids in it’s membrane?
Mature red blood cells cannot synthesise their own lipids.
What can red blood cell membrane proteins be classified as?
Integral proteins:
- Sodium/potassium ATPase
Peripheral proteins:
- Haemoglobin
- Spectrin
- Actin
What is hereditary spherocytosis?
An example of a primary membrane disorder, which is common in people of northern European ancestry (1 in 5000). HS caused by defects in either (or both) spectrin or Ankyrin.
What is spectrin?
Large constituent of the erythrocyte cytoskeleton. A heterodimer composed of alpha and beta sub-units (alpha gene is on Chr 1q, beta is on Chr 14q).
Alpha-spectrin is normally produced at 4x the rate of beta-spectrin.
Because of this, heterozygous defects in alpha-spectrin are clinically silent.
What is ankyrin?
A protein in RBCs that anchors spectrin heterodimers to the membrane. Gene is found on Chr 8p.
some HS patients have co-deficiency of ankyrin and spectrin.
What clinical presentations are there in hereditary spherocytosis?
There are similar symptoms to other anaemias, so lethargy, weakness, breathlessness, etc.
As well as usual anaemia symptoms, Jaundice will be present as well as splenomegaly (enlarged spleen).
Why is jaundice present in HS?
How does splenomegaly occur in HS?
What abnormalities are present in blood content in a patient with hereditary spherocytosis?
Hb can be normal or <90 g/L depending of severity.
Where in the spleen is the main site of senescent red blood cell removal?
The red pulp.
How does the spleen process red blood cells?
How is osmotic fragility affected in hereditary spherocytosis?
What key cell components do red blood cells lack?
Mature red blood cells lack nuclei, mitochondria and ribosomes.
How can the lack of important cell components affect a red blood cell?
Due to no mitochondria, RBCs are reliant on glycolysis. As well as relying on biochemical pathways to protect against oxidative damage.
What is the Embden-Meyerhof pathway?
What is methaemoglobinemia?
A high presence of methaemaglobin in the blood. Due to
What can a pyruvate kinase deficiency cause?
What are the clinical presentations of pyruvate kinase deficiency?
What is Favism?
What genes are associated with glucose 6 phosphate dehydrogenase deficiency?
GD A- (found in ~20% of populations of african decent)
GD med (found in mediterranean and levantine populations)
Gd canton (found in chinese populations)
What is autoimmune haemolysis?
An immune mediated haemolysis resulting from production of antibodies that bind to red cell surfaces.
