Lecture 4: Disorders of Red Blood Cell Survival

Question 1

How long do red blood cells survive on average in circulation?

Answer 1

~120 days

Question 2

What happens as red blood cells age?

Answer 2

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.

Question 3

What classifications of haemolytic disorders are there?

Answer 3

Site of haemolysis:
- Extravascular
- Intravascular
Intrinsic or extrinsic to the red cell
Nature or defect
Inherited or acquired
Acute or chronic

Question 4

What is a haemolytic disorder?

Answer 4

Any disorder in which the lifespan of red blood cells is reduced.

Question 5

How long will red blood cells survive in sickle cell anaemia?

Answer 5

~20 days, compared to the usual 120 days.

Question 6

What are intrinsic haemolytic disorders?

Answer 6

Haemolytic disorders caused by genetics. This can be further sub-classified:
- Disorders of globin synthesis/structure
- Primary membrane disorders
- Enzyme disorders

Question 7

What is the composition of a RBC membrane?

Answer 7

50% protein
10% carbohydrates
40% lipids (30% cholesterol, 10% free fatty acids, and 60% phospholipids)

Question 8

What problems does a red blood cell have with lipids in it’s membrane?

Answer 8

Mature red blood cells cannot synthesise their own lipids.

Question 9

What can red blood cell membrane proteins be classified as?

Answer 9

Integral proteins:
- Sodium/potassium ATPase

Peripheral proteins:
- Haemoglobin
- Spectrin
- Actin

Question 10

What is hereditary spherocytosis?

Answer 10

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.

Question 11

What is spectrin?

Answer 11

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.

Question 12

What is ankyrin?

Answer 12

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.

Question 13

What clinical presentations are there in hereditary spherocytosis?

Answer 13

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).

Question 14

Why is jaundice present in HS?

Question 15

How does splenomegaly occur in HS?

Question 16

What abnormalities are present in blood content in a patient with hereditary spherocytosis?

Answer 16

Hb can be normal or <90 g/L depending of severity.

Question 17

Where in the spleen is the main site of senescent red blood cell removal?

Answer 17

The red pulp.

Question 18

How does the spleen process red blood cells?

Question 19

How is osmotic fragility affected in hereditary spherocytosis?

Question 20

What key cell components do red blood cells lack?

Answer 20

Mature red blood cells lack nuclei, mitochondria and ribosomes.

Question 21

How can the lack of important cell components affect a red blood cell?

Answer 21

Due to no mitochondria, RBCs are reliant on glycolysis. As well as relying on biochemical pathways to protect against oxidative damage.

Question 22

What is the Embden-Meyerhof pathway?

Question 23

What is methaemoglobinemia?

Answer 23

A high presence of methaemaglobin in the blood. Due to

Question 24

What can a pyruvate kinase deficiency cause?

Question 25

What are the clinical presentations of pyruvate kinase deficiency?

Question 26

What is Favism?

Question 27

What genes are associated with glucose 6 phosphate dehydrogenase deficiency?

Answer 27

GD A- (found in ~20% of populations of african decent)

GD med (found in mediterranean and levantine populations)

Gd canton (found in chinese populations)

Question 28

What is autoimmune haemolysis?

Answer 28

An immune mediated haemolysis resulting from production of antibodies that bind to red cell surfaces.